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LIBRO DEGLI ABSTRACTS

Congress Proceedings

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COMITATO SCIENTIFICO

AIRO AIRB Commissione Scientifica


Presidente Presidente Coordinatore
Stefano M. Magrini Monica Mangoni Renzo Corvò

Presidente Eletto AIRO GIOVANI Michela Buglione di Monale e Bastia


Coordinatore
Vittorio Donato Pierfrancesco Franco

Consiglio Direttivo
Domenico Genovesi
Isacco Desideri Barbara A. Jereczek-Fossa

Consiglio Direttivo
Andrea R. Filippi Icro Meattini
Maria Antonietta Gambacorta Stefano Pergolizzi
Paolo Borghetti
Giuseppe Iatí
Francesca De Felice
Alessandro Magli
Carlo Greco
Marcello Mignogna
Valerio Nardone

ESTRO
Luigi Marafioti
Roberto Pacelli

Segretario alla Presidenza


Umberto Ricardi
Vincenzo Valentini
Michela Buglione di Monale e Bastia

Segretario Amministrativo
Stefano Pergolizzi

Coordinatori Gruppi Regionali Coordinatori Commissione Ministeriale LEA


Gruppi di Studio AIRO Lorenzo Livi
Paolo Bastiani

Presidente Fondazione S.N.R


Luigi Corti Filippo Alongi
Maria F. Dedola Cynthia Aristei
Marco Lioce Francesco Cellini
Giovanna Mantello Antonella Ciabattoni Francesco Lucà
Luigi Marafioti Pierfrancesco Franco

Rappresentante Professori
Franco Marletta Monica Mangoni

Ordinari MED/36
Alessandra Mirri Mariangela Massaccesi
Maria Grazia Ruo Redda Piera Navarria
Vincenzo Ravo Fabiola Paiar
Sandro Tonoli Vieri Scotti Vincenzo Tombolini
Luca Tagliaferri

SEGRETERIA EDITORIALE SEGRETERIA ORGANIZZATIVA


SEGRETERIA AIRO
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INDEX

Programme ................................................................................................................ 1

Selected Oral Communications ................................................................................30

Oral Communications...............................................................................................37

Discussed Poster.....................................................................................................107

Poster ......................................................................................................................130
L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Programme

early-stage HL includes short course of multiagent


chemotherapy followed by low-dose involved site RT.
NEW CHALLENGES FOR MODERN

Dosimetric benefits have been achieved with the


RADIOTHERAPY IN LONG-TERM SURVIVING

introduction of different intensity modulated RT


PATIENTS: LATE TOXICITIES AND QUALITY

(IMRT) techniques (Butterfly-Volumetric Arc Therapy


OF LIFE
G.C. Iorio1, S. Martini1, 1V. De Luca1, F. Arcadipane2,
S. Bartoncini2, M. Levis1, P. Franco1, U. Ricardi1 and Helical Tomotherapy).3 Moreover, the employment
1Department of Oncology, Radiation Oncology,
of the Deep inspiration breath-hold (DIBH) technique,
especially combined with IMRT, clearly showed the
University of Turin; 2Department of Oncology, possibility to decrease the estimated mean doses to the
Radiation Oncology, AOU Citta’ della Salute e della whole heart and to its substructures (particularly coro-
Scienza, Turin, Italy nary arteries and left ventricle) and, as well, to the lungs
Radiotherapy (RT) is an effective anticancer agent. when compared with Free-Breathing.4
The current paradigm of research is to minimize radia- Promising results (but still preliminary) have also
tion-induced toxicities, particularly late-effects com- been reported when treating HL patients with intensity
promising quality of life (QoL) and sequelae among modulated Proton therapy.5
long-term survivors,1 while keeping optimal disease Focusing on HNC patients, technological RT
control rates. upgrades led to lower acute and late toxicity profiles,
Modern RT planning and delivery techniques repre- with subsequent improved treatment compliance and
sent the key to achieve this target. Herein, we discuss quality of life (QoL).6
modern RT approaches in two different clinical set- Of interest, promising results have been reported
tings: with the employment of multivariable normal tissue
• reducing the risk of cardiovascular disease and sec- complication probability (NTCP) models for late swal-
ondary cancers when treating young patients affect- lowing dysfunction, 6 months after completion of treat-
ed with mediastinal Lymphomas, particularly ment (swallowing sparing-IMRT).7 Moreover, proton
Hodgkin Lymphoma (HL); therapy, given the potential dosimetric advantages
• improving late toxicity profile in Head and Neck when compared with photons (Bragg Peak), represents
Cancer (HNC) patients. a promising approach for HNC patients, potentially
Young patients with a long life expectancy are at achieving a clinical benefit in terms of improved local
higher risk of developing cardiovascular disease and tumor control and prevented/reduced radiation- induced
secondary cancers after treatment for mediastinal HL. side effects, considering the better sparing of critical
Historical long-term follow- up data showed that these organs (especially oral cavity and major salivary
survivors have an increased risk of late morbidity and glands).8,9 Results-based evidences from prospective
mortality, primarily caused by cardiovascular disease randomized trials comparing IMRT and proton beam
and lung and breast cancer.2 Nowadays, treatment for therapy are awaited.10

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Programme

Further evidences are awaited regarding how to tar-


get optimal outcomes in terms of QoL and late toxicity
REIRRADIATION IN CLINICAL ONCOLOGY: FROM

profile in both HL and HNC patients.


RADIOBIOLOGICAL CONSIDERATIONS TO ASSO-
CIATION WITH NEW DRUGS
F. Gregucci
References Radiation Oncology Department, F. Miulli General
Regional Hospital, Acquaviva delle Fonti, Bari, Italy
1. Matthew J. Krasin, Louis S. Constine, Debra L. Friedman,
Lawrence B. Marks. Radiation- Related Treatment Effects In recent years, thanks to the development of more
Across the Age Spectrum: Differences and Similarities or effective and fewer side effects radiation-systemic
What the Old and Young Can Learn from Each Other. Semin
Radiat Oncol 20:21-29, 2010. treatments, overall survival in cancer patients has
2. Aleman BM, van den Belt-Dusebout AW, Klokman WJ, et al. increased considerably and the interest in radiation has
Long- term cause-specific mortality of patients treated for grown. In order to make the oncological disease a
Hodgkin’s disease. J Clin Oncol 2003;21:3431-3439. chronic condition, the correct framing and treatment of
3. Christian Fiandra, Andrea Riccardo Filippi, Paola Catuzzo,
Angela Botticella, Patrizia Ciammella, Pierfrancesco Franco, the oligometastatic and oligoprogressive disease that
Valeria Casanova Borca, Riccardo Ragona, Santi Tofani and often requires a second (or third) radio-oncological
Umberto Ricardi. Different IMRT solutions vs. 3D- treatment, is becoming relevant. In fact, a therapeutic
Conformal Radiotherapy in early stage Hodgkin’s lym- shift has progressively been observed from the purely
phoma: dosimetric comparison and clinical considerations.
Radiation Oncology 2012, 7:186. palliative aim of reirradiations on painful bone metas-
4. Peter M. Petersen, Marianne C. Aznar, Anne K. Berthelsen, tases, for a curative purpose of retreatment on numer-
Annika Loft, Deborah A. Schut, Maja Maraldo, Mirjana ous districts and for all solid cancers. Re-irradiation is
Josipovic, Thomas L. Klausen, Flemming L. Andersen & characterized by a narrow therapeutic window in which
Lena Specht. Prospective phase II trial of image-guided
radiotherapy in Hodgkin lymphoma: Benefit of deep inspira- it is necessary to accurately weigh the dose to maximize
tion breath-hold. Acta Oncologica, 54:1, 60-66. 2015. efficacy and reduce toxicity, especially if the total
5. Christian Baues, Simone Marnitz, Andreas Engert, Wolfgang cumulative dose of the various cycles is high.
Baus, Karolina Jablonska, Antonella Fogliata, Andrés Reirradiation tends to pose even greater challenges and
Vásquez-Torres, Marta Scorsetti and Luca Cozzi. Proton ver-
sus photon deep inspiration breath hold technique in patients is therefore offered restrictively to highly selected
with hodgkin lymphoma and mediastinal radiation. patients on a case-by-case basis. Normal tissue dose
Radiation Oncology (2018) 13:122. limits are still an active area of investigation. However,
6. Christopher M Nutting, James P Morden, Kevin J examples of potentially useful indications have been
Harrington, Teresa Guerrero Urbano, Shreerang A Bhide,
Catharine Clark, Elizabeth A Miles, Aisha B Miah. Parotid- published. Clinical and experimental studies suggest
sparing intensity modulated versus conventional radiothera- that specific normal tissues can tolerate a considerable
py in head and neck cancer (PARSPORT): a phase 3 multi- radiation dose. From a technical point of view, in the
centre randomised controlled trial. The Lancet Oncology
2011; 12: 127–36. case of reirradiation, an optimal dose conformation to
7. Miranda E.M.C. Christianen , Arjen van der Schaaf , Hans the planning target volume is required. For radiobiolog-
Paul van der Laan , Irma M. Verdonck-de Leeu, Patricia ical reasons - in order to reduce the risk of late effects -
Doornaert , Olga Chouvalova , Roel J.H.M. Steenbakkers , hyperfraction protocols should be applied to curative
Charles René Leemans , Sjoukje F. Oosting , Bernard F.A.M.
van der Laan , Jan L.N. Roodenburg , Ben J. Slotman , treatments. Alternatively, hypofractionated schedules to
Hendrik P. Bijl , Johannes A. Langendijk M.E.M.C. small volumes can be considered in a highly conforma-
Christianen et al. Swallowing sparing intensity modulated tive and image-guided stereotactic approach.
radiotherapy (SW-IMRT) in head and neck cancer: Clinical Furthermore, the treatment with protons and heavy
validation according to the model-based approach.
Radiotherapy and Oncology 118 (2016) 298–303. ions, due to their peculiar physical and radiobiological
8. Jonathan E Leeman, Paul B Romesser, Ying Zhou, Sean characteristics, plays a key role in this context. The
McBride, Nadeem Riaz, Eric Sherman, Marc A.Cohen, Oren association with new drugs, immunotherapy and target
Cahlon, Nancy Lee. Proton therapy for head and neck can- therapy is a promising field of research, as recent evi-
cer: expanding the therapeutic window. The Lancet
Oncology 2017. 18(5):e254- e265. dence seems to show on the one hand an increase in
9. van de Water TA, Lomax AJ, Bijl HP, et al. Potential benefits efficacy due to a synergy of treatments, and on the other
of scanned intensity- modulated proton therapy versus hand a reduction in toxicity.
advanced photon therapy with regard to sparing of the sali-
vary glands in oropharyngeal cancer. Int J Radiat Oncol Biol
Phys 2011; 79: 1216-24.
10. Randomized Trial of Intensity-Modulated Proton Beam
Therapy (IMPT) Versus Intensity-Modulated Photon
PRACTICE-CHANGING TRIALS IN RADIOTERAPIA
Therapy (IMRT) for the Treatment of Oropharyngeal Cancer
ONCOLOGICA 2019
of the Head and Neck. NCT01893307. B.A. Jereczek-Fossa
Department of Oncology and Hemato-oncology,
University of Milan, Milan; Division of Radiotherapy,
IEO European Institute of Oncology, IRCCS, Milan,
Italy
The medical knowledge is rapidly changing. New
evidence is available based on the studies published in
2018-2019 and including radiotherapy. 18234 new
reports on cancer radiotherapy are available at the 30th

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

June 2018 (since 1st January 2018). 650 reports regard oropharyngeal cancer (NRG Oncology RTOG 1016):
clinical trials. Among the most significant studies are a randomised, multicentre, non-inferiority trial.
the following examples. Lancet. 2019 Jan 5;393(10166):40-50.
Breast cancer: Confirmation of the efficacy and Compared with the standard cisplatin regimen,
safety of APBI for low-risk DCIS: APBI-IMRT- cetuximab showed no benefit in terms of reduced toxi-
Florence phase 3 trial (NCT02104895). Becherini C et city, but instead showed significant detriment in terms
al. External accelerated partial breast irradiation for of tumour control. Cisplatin and radiotherapy should be
ductal carcinoma in situ: long-term follow-up from a used as the standard of care for HPV-positive low-risk
phase 3 randomized trial. Tumori. 2019 patients who are able to tolerate cisplatin. Mehanna H
Jun;105(3):205-209. Postmastectomy radiotherapy led et al. Radiotherapy plus cisplatin or cetuximab in low-
to more local (chest wall) symptoms up to 2 years pos- risk human papillomavirus-positive oropharyngeal can-
trandomisation compared with no radiotherapy, but the cer (De-ESCALaTE HPV): an open-
difference between groups was small: SUPREMO label randomised controlled phase 3 trial. Lancet. 2019
TRIAL ISRCTN registry, number ISRCTN61145589. Jan 5;393 (10166):51-60
Velikova G et al. Quality of life after Cochlear-sparing IMRT reduced the radiation dose
postmastectomy radiotherapy in patients with interme- below the accepted tolerance of the cochlea, but this did
diate-risk breast cancer (SUPREMO): 2-year follow-up not lead to a reduction in the proportion of patients with
results of a randomised controlled trial. Lancet clinically relevant hearing loss. Nutting CM et al.
Oncol. 2018 Nov;19(11):1516-1529. Encouraging clin- Results of a multicentre randomised controlled trial of
ical outcome of a post-operative single fraction of APBI cochlear-sparing intensity-modulated radiotherapy ver-
by multicatheter interstitial high dose-rate brachythera- sus conventional radiotherapy in patients with
py. Kinj R. et al. Single fraction of accelerated partial parotid cancer (COSTAR; CRUK/08/004). Eur
breast irradiation in the elderly: early clinical outcome. J Cancer. 2018 Nov;103:249-258.
Radiat Oncol. 2018 Sep 12;13(1): 174. The list of new significant studies will be updated at
Lung cancer: Radiotherapy induces responses the moment of the presentation.
of lung cancer to CTLA-4 blockade. Formenti SC et al.
Nat Med. 2018 Dec;24(12):1845-1851. Durvalumab
therapy resulted in significantly longer overall survival
than placebo. No new safety signals were identified.
THE ROLE OF THE RADIATION ONCOLOGIST IN

PACIFIC trial. Antonia SJ et al. Overall Survival with


MULTIDISCIPLINARY TEAMS, AND THE IMPACT

Durvalumab after Chemoradiotherapy in Stage III


OF HOSPITAL GUIDELINES IN PATIENTS’ OUTCOME
V. Donato
NSCLC. N Engl J Med. 2018 Dec 13;379 (24):2342-
2350 Azienda Ospedaliera San Camillo Forlanini, Roma,
Prostate cancer: Evidence suggests that prostate Italy
radiotherapy improves overall survival for men with Aims: To investigate the role of the radiation oncol-
metastatic prostate cancer who have a low metastatic ogists inside muldisciplinary oncologic teams, and to
burden, but not for unselected patients. Prostate radio- assess the impact on patients’ outcomes of a complete
therapy should be a standard treatment option for men care pathway provided by institutions.
with newly diagnosed disease with a low metastatic Methods: We undertook a literature search of
burden. Parker CC et al. Radiotherapy to the primary PubMed using search terms such as “multidisciplinary
tumour for newly diagnosed, metastatic prostate cancer team”, “meetings” or “oncology decision making”. In
(STAMPEDE): a randomised controlled phase 3 trial. order to identify relevant literature on the issue, we
Lancet. 2018 Dec 1;392(10162):2353-2366. searched for systematic reviews, meta-analysis and
Glioblastoma: lomustine-temozolomide chemother- comparative studies, assessing the impact of the multi-
apy might improve survival compared with temozolo- disciplinary team (MDT) meetings and/or of an institu-
mide standard therapy in patients with newly diagnosed tionalized health care pathway on patient’s diagnosis,
glioblastoma with methylated MGMT treatment and outcomes.
promoter. Herrlinger U et al. Lomustine-temozolomide Results: To find studies assessing MDT effective-
combination therapy versus standard temozolomide ness has proven difficult, as the majority of studies on
therapy in patients with newly diagnosed glioblastoma the issue are retrospective monocentric analysis.
with methylated MGMT promoter (CeTeG/NOA-09): However, we focused on those two meta-analyses
a randomised, open-label, phase 3 trial. Lancet. 2019 and other thirty methodologically valid studies we
Feb 16;393(10172):678-688. found that were confronting patient’s diagnosis, treat-
Head and neck cancer: For patients with HPV-pos- ment and outcomes, before and after the implementa-
itive oropharyngeal carcinoma, radiotherapy plus tion of MDTs and/or institutionalized care pathway, and
cetuximab showed inferior overall survival and pro- our results showed that the impact of both was signifi-
gression-free survival compared with radiotherapy plus cant in all cited items. Between 4% and 35% of patients
cisplatin. Radiotherapy plus cisplatin is the standard of discussed had changes to diagnostic reports and the per-
care for eligible patients with HPV-positive oropharyn- centage of patients who underwent changes in treatment
geal carcinoma. Gillison et al. Radiotherapy plus cetux- plans range from 19% to 34.5%. Patients discussed in
imab or cisplatin in human papillomavirus-positive MDT meetings, were more likely to: receive neoadju-

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Programme

vant or adjuvant treatment; be referred to other disci- outcome; for this reason, imaging plays a key role in the
plines; be managed with greater guidelines adherence recognition of this entity.
and to get a more curative management. Conventional MR imaging is limited in the differen-
Conclusions: We found some prospective studies, tiation of early progression of disease and pseudopro-
assessing different cancer population, reporting a sig- gression because both can show increased enhancement
nificant association between MDT discussion and sur- after contrast medium infusion and perilesional edema.
vival, especially in colorectal cancer and lung cancer To overcome this problem, several advanced MR imag-
patients. There is a need to improve team work. A real ing techniques have been evaluated.
involvement of physicians from specialities other that Diffusion-weighted imaging (DWI) is a functional
surgery or medical oncology leads to better outcomes sequence that depends on the microscopic mobility of
for cancer patients. We also recognized that radiation the water. Apparent diffusion coefficient (ADC) values
oncologists are under-represented in the literature con- were noted to be lower in the recurrent tumor tissue;
cerning MTDs, and this requires a reflection on our however, heterogeneity of tumor content limits the
responsibilities as a cancer care specialists. diagnostic performance of this data. A study of Chu and
coll. found that histogram analysis based on the ADC of
References the entire enhancing lesion may be a useful tool in the
B. Pillay et al. The impact of multidisciplinary team meetings on differentiation of true progression from pseudoprogres-
patient assessment, management and outcomes in oncology sion in glioblastomas.
settings: A systematic review of the literature. Cancer
Treatment Reviews 42 (2016) 56–72
Brown et al. A multidisciplinary team-oriented intervention to
increase guideline recommended care for high-risk prostate
cancer: A stepped-wedge cluster randomised implementation
trial Implementation Science (2018) 13:43
Colasante et al. Interdisciplinary decision making in prostate can-
cer. Oncology letters 15: 1823-1828, 2018
M.J. Rogers et al. Comparison of outcomes for cancer patients
discussed and not discussed at a multidisciplinary meeting.
Public Health 149 (2017) 74e80
Cristiana Bergamini et al. Does a multidisciplinary team
approach in a tertiary referral centre impact on the initial
management of head and neck cancer? Oral Oncology 54
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Tayana Soukup et al. Successful strategies in implementing a
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Raghid N. Charara et al. Practice and Impact of Multidisciplinary
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J Glob Oncol 3, 2016 by American Society of Clinical
Oncology
Yara L. Basta et al. The Value of Multidisciplinary Team
Meetings for Patients with Gastrointestinal Malignancies: A
Figure. GBM. Firts control MR after surgery and chemio-radiation therapy. SE T1 after
Systematic Review. Ann Surg Oncol (2017) 24:2669–2678
contrast medium (a-b) shows an area of enhancement in the right temporal lobe and
Jeffrey C. Liu et al. The Impact of the Multidisciplinary Tumor
Board on Head and Neck Cancer Outcomes. Laryngoscope,
in the insula. MR perfusion shows an high blood volume area in the temporal lobe

00:1–5, 2019 The Laryngoscope 2019 The American


as recurrence (c- arrow) and low blood volume area in the insula as pseudoprogres-

Laryngological, Rhinological and Otological Society, Inc.


sion (d – arrow).
Thomas V. Bilfinger et al. Survival Outcomes Among Lung
Cancer Patients Treated Using a Multidisciplinary Team
Approach. Clinical Lung Cancer, 2018 Elsevier Inc. Perfusion MR imaging evaluates vascularity and
vessels’ permeability in the lesion. Dynamic
Susceptibility Contrast-Enhanced (DSC) is the most
used method for brain perfusion MRI; several studies
found that the main DSC parameter, the relative cere-
RADIOLOGIC FEATURES OF TRUE PROGRESSION

bral blood volume (rCBV), is higher in true progression


VS PSEUDOPROGRESSION IN GLIOMA AND

than in pseudoprogression. An alternative technique is


BRAIN METASTASES
A. Vidiri1, E. Leone2
1IRCCS Regina Elena National Cancer Institute; Dynamic Contrast-Enhanced (DCE), which measures
2IRCCS F. Policlinico Gemelli IRCCS, Rome, Italy vascular permeability; some of the pharmacokinetics
parameters, such as the volume transfer constant
Pseudoprogression is a treatment-related reaction, (Ktrans) and the extravascular-extracellular volume
characterized by an increase in enhancing lesion size (Ve), were significantly higher in true progression of
and/or edema, followed by subsequent improvement or glioblastoma than in pseudoprogression. MR spec-
stabilization. Pseudoprogression usually occurs in the troscopy is an advanced MR imaging that offers a bio-
2- to 6-month period after chemio-radiotherapy, and it chemical pattern analysis of the tumors. Differential
seems to be induced by a local tissue reaction, with diagnosis is challenging because both type of lesions
increased edema and vessel permeability. Several stud- (progression disease and pseudoprogression) can pres-
ies showed that pseudoprogression results in a better ent decrease of N-acetyl-aspartate (NAA), elevation of

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Choline (Cho) and high lactate/lipid values; however, it under-stressed. Although several reports have suggest-
is found that Cho/NAA ratio has high diagnostic accu- ed a reasonable efficacy and safety profile of re-irradi-
racy in the distinction of the two entities. ation, most of these have a small sample size with
In conclusion, advanced MR imaging plays a key inconsistent findings. A recent expert consensus report
role in the assessment of treatment response. surveying 13 experienced radiation oncologists showed
that there is significant variability in patient selection
References for re-irradiation and in preferred radiation regimens.7
Chu HH, Choi SH, Ryoo I, et al. Differentiation of True A systematic review shows an OS-6, OS-12, PFS-6
Progression from Pseudoprogression in Glioblastoma and PFS-12, from time of re-irradiation of 73% , 36%,
Treated with Radiation Therapy and Concomitant 43% and 17% respectively [8]. The overall toxicity rate
Temozolomide: Comparison Study of Standard and High-b- was considered to be low (range 4–10%) although
Value Diffusion-weighted Imaging. Radiology 2013;
269:831-840. Grade 3+ toxicity was not reported uniformly. The opti-
Fatterpekar GM, Galheigo D, Narayana A, et al. Treatment- mal dose-fractionation regimen remains unclear and a
Related Change Versus Tumor Recurrence in High-Grade wide range of dose prescriptions were used. No differ-
Gliomas: A Diagnostic Conundrum—Use of Dynamic ence based on the median EQD2 was found in system-
Susceptibility Contrast-Enhanced (DSC) Perfusion MRI.
AJR 2012; 198:19–26. atic review and, interestingly, a short fractionation
Griffith B, Jain R. Perfusion Imaging in Neuro-Oncology: Basic (radiosurgery or hypofractionated raduation with ≤5
Techniques and Clinical Applications. Magn Reson Imaging fractions) regimen seems to be associated with an
Clin N Am 2016; 24:765–779. improved PFS-6.8 In our practice, we perform a highly
Hygino da Cruz Jr LC, Rodriguez I, Domingues RC, et al.
Pseudoprogression and Pseudoresponse: Imaging Challenges conformal technique with a hypofractionated regimen
in the Assessment of Posttreatment Glioma. AJNR 2011; (such as 30 Gy in 5 fractions), taking into account the
32:1978-85. volume and location of the recurrent tumor. Our Phase
Knitter JR, Erly WK, Stea BM, Lemole GM, Germano IM, I trial (GLIORAD), which is currently investigating the
DoshI AH, Nael K: Interval Change in Diffusion and
Perfusion MRI Parameters for the Assessment of safety of dose escalated re-irradiation (50 Gy in 5 frac-
Pseudoprogression in Cerebral Metastases Treated With tions), has reached the planned accrual and should help
Stereotactic Radiation AJR 2018; 211: 1-8. clarify the the best way to manage these patients.
Mangla R, Singh G, Ziegelitz D, et al. Changes in relative cere- In conclusion, local re-irradiation has been estab-
bral blood volume 1 month after radiation-temozolomide
therapy can help predict overall survival in patients with lished as a feasible option for recurrent GBL in all ages
glioblastoma. Radiology 2010; 256:575–84. with safety, tolerability, and effectiveness both in sur-
Thust SC, van den Bent MJ, Smits M. Pseudoprogression of brain vival and quality of life regardless of fractionation
tumors. J Magn Reson Imaging 2018; 48:571–589. schedule. Prospective trials are required to assess
Yun TJ, Park CK, Kim TM, et al. Glioblastoma Treated with
Concurrent Radiation Therapy and Temozolomide neuro-cognitive and quality-of-life endpoints taking
Chemotherapy: Differentiation of True Progression from into account the molecular profile of the recurrent
Pseudoprogression with Quantitative Dynamic Contrast- tumor (O[6]-methylguanine-DNA methyltransferase
enhanced MR Imaging. Radiology 2015; 274:830-840. (MGMT) methylation, EGFR amplification, BRAF
V600E mutation) in order to guide the integrated man-
agementfor these patients.

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rence, in a favorable location (i.e., away from brain- 8. Kazmi F et al. Re-irradiation for recurrent glioblastoma
(GBM): a systematic review and meta-analysis. J
stem), re-irradiation may be a suitable option. However, Neurooncol. 2019 Mar;142(1):79-90.
the fear of treatment-related toxicity makes this option

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3 Nieder C, Langendijk JA, Guckenberger M, Grosu AL:


Second re-irradiation: a narrative review of the available
BRAIN METASTASES RE-IRRADIATION: INDICA-
clinical data. Acta Oncol. 2018, 57:305-310.
TIONS, NEW TECHNIQUES AND POTENTIAL TOXI-
CITIES
V. Pinzi
Fondazione IRCCS Istituto neurologico Carlo Besta,
LOCOREGIONALLY ADVANCED DIFFERENTIATED
Neurosurgery Department, Radiotherapy Unit, Milan, THYROID CANCER: INDICATIONS OF RADIOAC-
Italy TIVE IODINE AND EXTERNAL BEAM

Aims: Although historically associated with a medi-


RADIOTHERAPY
C. Gobitti, E. Borsatti1, E. Minatel, G. Fanetti,
an survival of only a few months, long-term survival G. Franchin
after the diagnosis of brain metastases is now changed
and it is significantly improved.1-2 However, along with Radiation Oncology Department, 1Nuclear Medicine
long-term survival, both local and distant brain relapse Department; Centro di Riferimento Oncologico (CRO)
can occur after longer and variable time intervals, being IRCCS, National Cancer Institute, Aviano, Italy
in need of additional radiotherapy. Neverthless, re-irra- Aims: To review the main literature in order to
diation of brain metastases after radiosurgery to the determine the indications for the use of radioiodine and
same target volume is still a controversial approach.3 external beam radiotherapy (EBRT) in locally advanced
The aim of this study is to summarize the results of clin- differentiated thyroid carcinoma (LADTC) of follicular
ical studies on brain metastes re-irradiation in terms of origin.
survival, local control and toxicity. Methods: Given the relative rarity of the disease
Methods: A literature review was carried out based and its indolent behaviour with the occurrence of
on PubMed search. The keywords used were "reirradi- relapse even decades after treatment, no randomized
ation", "re-irradiation", “repeat radiotherapy” “salvage clinical trials have been conducted and concluded.
radiotherapy” and “salvage radiosurgery” combined Information about the usefulness of radioiodine and
with “brain metastases”, "secondary brain tumor" and EBRT in LADTC can be obtained only by retrospective
“cerebral metastases”. The eligibility criteria were: 5 observational studies, based on single-institution expe-
analysed patients at least; English language; local con- riences, and usually covering several decades.
trol, survival and/or toxicity as primary end-points of Results: the patient population is usually heteroge-
the study; minimum follow-up of 3 months. A descrip- neous, patients are staged according to different TNM
tive statistical analysis was performed. editions and with various diagnostic tools and treated
Results: Ten retrospective and 1 prospective studies with technologies of varying degrees of complexity.
were identified and analysed. All references were With these limitations the main literature is reviewed in
checked for further search. Where reported, the median order to give recommendations on the use of radioio-
follow-up ranged from 8,8 to 14 months. The one-year dine and EBRT.
survival rates ranged from 38% to 91%, (median 65%). Conclusions: The most important therapeutic tool
The one-year local control rates ranged from 68% to in LADTC remains surgery, which in few cases
88% (median 79%). The overall radionecrosis rate was requires organ sacrifice to be radical. The use of
20%, ranging from 10% to 38%. No significant neuro- radioiodine with adjuvant intent has a consolidated role
logical toxicity was reported. However, data related to in LADTC and international guidelines substantially
neurocognitive function or quality of life were not iden- agree about its use. Many published retrospective
tified. observational studies indicate that EBRT can improve
Conclusions: While the data are scarce, re-irradia- locoregional control but, in the absence of a strong
tion of brain metastes seems to be a viable and safe evidence, the use of adjuvant EBRT needs a careful
option for patients who are not ideal candidates for sal- evaluation of the risk of recurrence and of acute and late
vage surgery. However, the retrospective design of the toxicities. In addition, the studies indicate that the fol-
studies and the different doses and fractionation used lowing prognostic factors should be considered: pT4
cannot allow us to draw any definitive conclusions. stage, R1 and R2 surgery, extracapsular invasion of
Future studies are required to clarify the role of re-irra- LN, disease refractory to radioiodine and patient age.
diation of brain metastases and its impact on disease
and patient-related outcomes. References
References 1. Biermann M et al. Clinical outcomes of adjuvant external-
beam radiotherapy for differentiated thyroid cancer - results
1. Sperduto PW, Deegan BJ, Li J, et al.: Effect of targeted ther- after 874 patient-years of follow-up in the MSDS-trial.
apies on prognostic factors, patterns of care, and survival in Nuklearmedizin 2009; 48(3):89-8.
patients with renal cell carcinoma and brain metastases. Int J 2. Brierley J et al. The role of external beam radiation and tar-
Radiat Oncol Biol Phys. 2018, 101:845-853. geted therapy in thyroid cancer. Sem Radiat Oncol
10.1016/j.ijrobp.2018.04.006 2012;22(3):254-262.
2. Ramakrishna N, Temin S, Chandarlapaty S, et al.: 3. Farahati J et al. Differentiated thyroid cancer. Impact of adju-
Recommendations on disease management for patients with vant external radiotherapy in patients with perithyroidal
advanced human epidermal growth factor receptor 2-positive tumor infiltration (stage pT4). Cancer 1996;77:172-180.
breast cancer and brain metastases: ASCO clinical practice 4. Haugen BR et al. American Thyroid Association
guideline update. J Clin Oncol. 2018, 36:2804- 2807. Management Guidelines for Adult Patients with Thyroid
10.1200/JCO.2018.79.2713 Nodules and Differentiated Thyroid Cancer: The American

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Thyroid Association Guidelines Task Force on Thyroid linked to a short overall survival (OS).7 The MOSCATI
Nodules and Differentiated Thyroid Cancer. Thyroid study denoted skeletal-related events (SRE) are more
2016;26(1):1-133.
5. Keum KC et al. The role of postoperative external-beam frequent in non-avid RAI disease.8 Besides, Andrade et
radiotherapy in the management of patients with papillary al.9 showed how the use of Zolendronic Acid could
thyroid cancer invading the trachea. IJROBP 2006;65:474- reduce chances of having SRE and impact OS as well.
480. From a retrospective study conducted by Wu et al.10
6. Lee EK et al. Postoperative simultaneous integrated boost-
intensity modulated radiation therapy for patients with combining 131I with other therapies may improve OS.
locoregionally advanced papillary thyroid carcinoma: pre- In addition to RAI therapy, lymphonodal, lung and
liminary results of a phase II trial and propensity score analy- brain metastases can be treated with surgery or with
sis. J Clin Endocrinol Metab 2015;100(3):1009-1017. stereotactic radiotherapy if lesions are macroscopically
7. Mangoni M et al. External beam radiotherapy in thyroid car-
cinoma: clinical review and recommendations of the AIRO evident or in cases of poorly differentiated disease. For
“Radioterapia Metabolica” Group. Tumori 2017;103(2):114- liver metastases, an unfrequent occurrence, interven-
123. tional tecniques5 are an option too. Tyrosine kinase
8. Perros P et al. British Thyroid Association. Guidelines for the inhibitors are used in cases of metastatic, quickly pro-
management of thyroid cancer. Clin Endocrinol (Oxf).
2014;81(Suppl 1):1-122. gressive (doubling time <1yr) and RAI-refractory dis-
9. Sawka AM et al. A Systematic Review and Metaanalysis of ease. PET-FDG imaging can provide additive data to
the Effectiveness of Radioactive Iodine Remnant Ablation CT imaging and shows to be an excellent tool in lesions
for Well-Differentiated Thyroid Cancer. J Clin Endocrinol detection and in the follow-up. In conclusion, RAI
Metab 2004;89(8):3668-3676.
10. Tuttle MR et al. Controversies, Consensus, and remains an irreplaceable therapy in metastatic DTC, but
Collaboration in the Use of 131-I Therapy in Differentiated a patient-tailored therapy should be considered, espe-
Thyroid Cancer: A Joint Statement from the American cially in older patients (>45 yrs), poorly differentiated
Thyroid Association, the European Association of Nuclear
Medicine, the Society of Nuclear Medicine and Molecular cancer and in case of BRAF or TERT mutations.
Imaging, and the European Thyroid Association. Thyroid
2019;29(4):461-470.
References
1. Tumino D, Frasca F, Newbold K Updates on the
Management of Advanced, Metastatic, and Radioiodine
Refractory Differentiated Thyroid Cancer Frontiers in
METASTATIC DISEASE IN DTC: INDICATIONS
Endocrinology November 2017 Vol 8 Article 312 www.fron-
TO 131I TREATMENT AND COMPLEMENTARY
THERAPIES tiersin.org
F. Monari1, A. Benini1,3, E. Lodi Rizzini1,2, 2. Slook O, Levy S, Slutzky-Shraga I et al. Long-Term
D. Vallerossa1,3, C. Scampoli1,3, A.G. Morganti1,3 Outcomes and Prognostic factors in patients with differenti-
ated thyroid carcinoma and bone metastates Endocrine
1Radiation Oncology Center, S.Orsola- Malpighi Practice- 2018-0465
Hospital, Bologna; 2Nuclear Medicine Center, 3. Jentzen W, Verschure F, van Zon A et al. 124I PET
Assessment of Responce of Bone Metastases to Initial
S.Orsola-Malpighi Hospital, Bologna; 3DIMES, Raioiodine Treatment of Differentiated Thyroid Cancer The
University of Bologna, Italy Journal of Nuclear Medicine Vol. 57 N. 10 October 2016
4. Nichols KJ, Robeson W, Yoshuda-Hay M et al. Alternative
Differentiated thyroid cancer (DTC) is an indolent Means of Estimating 131 I Maximum Permissible Activity to
tumor in the majority of cases. Even so, up to 10% of Treat Thyroid Cancer The Journal of Nuclear Medicine Vol.
patients will develop metastatic disease (MD).1 58 N. 10 October 2017
5. Cazzato RL, Garnon J, Koch G et al. Current role of inter-
Treatment with radioactive iodine (RAI) represents the ventional radioòogy in the management of visceral and bone
standard of care in metastatic DTC and usually a dose metastases from thyroid cancer Gland Surg2018;7 (2):80-88
equivalent to 7400 MBq is administrated. However, ret- 6. Duntas LH Thyroid cancer-related bone metastases: increas-
rospective and dosimetric studies have shown that only ingly good prospects for treatment Endocrine (2018) 61:1-3
https://doi.org/10.1007/s12020-080-1616-2
about one third of these patient can be cured with RAI. 7. Califano I, Deutsch S, Lowenstein A et al. Outcomes of
These are generally younger (<45 yrs), with well- dif- patiens with bone metsteses from differentiated thyroid can-
ferentiated disease and small tumoral dimensions (<1 cer Arch Endocrinol Metab. 2018: 62/1
cm).2 The remaining cases appear to be non-avid RAI 8. Mazziotti G, Formenti AM, Panarotto et al Real-life man-
agement and outcome of thyroid carcinoma-related bone
disease and this therapy can only have a cytoreductive metastases: results from a nationwide multicenter experience
effect. Dosimetric studies conducted with 124I3 or with Endocrine 2018 Jan; 59 (1): 90-101 Epub 2017 Nov 6
maximum permissible activity to protect bone marrow4 https://www.ncbi.nlm.nih.gov/pubmed/2911129
haven’t showed consistent results compared to stan- 9. Andrade F, Probstner D, Decnop M et al. The Impact of
Zoledronic Acid Radioactive Iodine therapy on Morbi-
dard-activity approach. Moreover, it’s important to Mortality of Patients with Bone Metastases Thyroid Cancer
evaluate risk-benefit assessment of repeating RAI treat- Derived from Follicular Cells Eur Thyroid J 2019;8:46-55
ment with a cumulative dose >600 MBq. MD repre- Published online October 3, 2018
sents a complex clinical scenario, where treatment is 10. Kim BW Multimodal Treatment of Thyroid Cancer Bone
Metastases Appears to Improve Survival as Compared to I-
usually patient-tailored and discussed in multidiscipli- 131 Alone Clin Thyroidol June 2019;31:250-252
nary team.5 RAI therapy is usually non curative and
integration between different methods (surgery, EBRT,
interventional techniques) is used to achieve better local
control. Focusing on bone metastases, affecting about
13% of patients,6 they are usually RAI-refractory and

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radioiodine refractory differentiated thyroid cancer. Clin


Endocr 2018; 88: 529-537.
RADIOACTIVE IODINE REFRACTORY DISEASE
Schmidt A, Iglesias L, Klain M et al. Radioactive iodine-refracto-
AND TREATMENT WITH TKI
F. Vianello, O. Lora ry differentiated thyroid cancer: an uncommon but challeng-
ing situation. 2017; 61 (1): 81-89.
UOC Radioterapia Istituto Oncologico Veneto IRCCS Berdelou A, Lamartina L, Klain M et al. Treatment of refractory
Padova thyroid cancer. Endocine-Related Cancer 2018; 25: 229-223.
Tuttle RM, Brose MS, Grande E et al. Novel concepts for initiat-
The incidence of differentiated thyroid cancer ing multitargeted kinase inhibitors in radioactive iodine
(DTC) has increased in the past decades and, irrespec- refractory differentiated thyroid cancer. Best Practice &
tive of whether overdiagnosis plays a role, there are Research Clinical endocrinology & Metabolism. 2017; 31:
295-305.
now more patients who need risk stratification of their Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus
disease. Most cases are associated with excellent prog- placebo in radioiodine-refractory thyroid cancer. N Eng J
nosis with survival rate of 95.8% at 5-year. Distant med. 2015; 372:621-630.
metastases (DM) are rare on presentation but are found
in 6-20% of patients in follow-up and this increases the
risk of cancer-specific mortality. On diagnosis of DM,
radioactive iodine (RAI) is usual first-line therapy fol-
MODERATE HYPOFRACTIONATION: CURRENT

lowed by TSH suppression. Progressive dedifferentia-


CLINICAL PRACTICE?
G. Timon
tion of DTC is accompanied by loss of the sodium
iodide symporter that is required for iodine uptake and Radiation Oncology Unit, AUSL - IRCCS di Reggio
poorly differentiated foci often exhibit parallel develop- Emilia, Italy
ment of 18 F-Fludeoxyglucose (FDG)-PET positivity. Hypofractionated radiotherapy (HRT) for prostate
When the DTC becomes or is intrinsically refractory to cancer seems to have a strong radiobiological rationale:
RAI, the prognosis is poor. Patients with DM that the low value of prostate cancer alpha/beta (estimated
retains RAI avidity have a 10-year survival of 60%, and approximately 1.5-2), slightly lower than adjacent nor-
survival falls to 10% when RAI avidity or responsive- mal tissues, should allow an improvement in therapeu-
ness are lost. RAI refractory disease occurs in less than tic ratio. Moreover, the use of a smaller number of frac-
5% of patients with DTC. The main criteria for consider tions is increasing, being convenient both for patients
a disease RAI refractory (with appropriate TSH level) and facilities. For these reasons HRT is considered a hot
are the lack of uptake in metastatic tissue, also in DM topic in radiation oncology. Several studies have com-
that previously were RAI avid, and the progression of pared conventional (CRT) and moderate HRT in the
disease despite significant RAI uptake. At times, the treatment of prostate cancer patients, and some are still
definition of “refractory” is in progress and other con- ongoing. Published data concerning the curative treat-
ditions may suggest the presence of refractory disease: ment of prostate cancer suggest a non-inferiority of
when RAI can be concentrated in some metastases but HRT, with some studies reporting a better outcome in
not others; in presence of high FDG uptake on PET terms of local or biochemical control, and no significant
scan; and in the cases of aggressive DTC histology. increase of toxicity, although a longer follow-up is
Those patients who have an unresectable primary DTC needed to assess both long-term outcome and late toxi-
tumor should also be included in this classification. city.
Limited treatment options are available for patients Post-operative HRT has also been suggested to be
with progressive and refractory DTC. Conventional feasible and safe, although some experiences reported a
chemotherapy has limited efficacy and significant toxi- higher rate of late genito-urinary toxicity.
cities. A greater understanding of the biology of DTC HRT is now widely performed in daily clinical prac-
has led to the development of “targeted” therapies, tice, both in curative and post-operative setting.
especially anti-angiogenic drugs and some target kinas-
es in the MAP kinase pathway. The optimal time to start References
these therapies is still a matter of debate, especially for
NCCN guidelines Version 1.2015 Prostate cancer.
asymptomatic patients. However systemic treatments European Association of Urology (EAU Guidelines on Prostate
should be started in patients with progression of meas- Cancer. Mottet N (Chair), Bellmunt J, Briers E, et al.;
urable lesions, as defined radiologically by RECIST cri- European Association of Urology 2015
teria, and must take into consideration tumor burden, Hegemann NS, Guckenberger M, Belka C, et al.
Hypofractionated radiotherapy for prostate cancer. Radiat
site of the lesions, symptoms, and the risk of local com- Oncol 2014;9:275.
plications. With these agents, partial remission were Koontz BF, Bossi A, Cozzarini C, Wiegel T, D’Amico A. A sys-
observed and even more importantly median progres- tematic review of hypofractionation primary management of
prostate cancer. Eur Urol 2015 Oct;68(4):683-91.
sion-free survival was prolonged in phase III trials Carvalho IT, Baccaglini W, Claros OR et al. Genitourinary and
when compared with placebo. gastrointestinal toxicity among patients with localized
prostate cancer treated with conventional versus moderately
References hypofractionated radiation therapy: systematic review and
meta-analysis. ACTA ONCOLOGICA 2018, VOL. 57, NO.
Nixon IJ, Whitcher MM, Palmer FL et al. The impact of distant 8, 1003–1010
metastases at presentation on prognosis in patients with dif- Yin Z, You J, Wang Y et al. Moderate hypofractionated radiother-
ferentiated carcinoma of the thyroid gland. Thyroid apy vs conventional fractionated radiotherapy in localized
2012;22:884-889. prostate cancer: a systemic review and meta-analysis from
Gild ML, Topliss DJ, Learoyd D et al. Clinical guidance for Phase III randomized trials. OncoTargets and Therapy

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2019:12 1259–1268. ,7,8 and systematic meta-analysis9 were recently pub-


Ferella L, limoncin E, Vittorini F et al. Are we ready for a para- lished.
digm shift from high-dose conventional to moderate
hypofractionated radiotherapy in intermediate-high risk Conclusion: Although randomized clinical trials
prostate cancer? A systematic review of randomized con- comparing SBRT with conventionally fractionated
trolled trials with trial sequential analysis. Critical Reviews radiotherapy are currently underway, the current body
in Oncology / Hematology 139 (2019) 75–82 of evidence allows the conclusion that extreme hypo-
Siepe G, Buwenge M, Nguyen NP et al. Postoperative
Hypofractionated Radiation Therapy in Prostate Carcinoma: fractionation is safe, effective and cost advantageous,
A Systematic Review. ANTICANCER RESEARCH 38: and should be considered in clinical practice.
1221-1230 (2018)
References
1. Extreme hypofractionation for early prostate cancer: Biology
meets technology. De Bari B, Arcangeli S, Ciardo D,
Mazzola R, Alongi F, Russi EG, Santoni R, Magrini SM,
EXTREME HYPOFRACTIONATION: WHAT FUR-

Jereczek-Fossa BA. On the behalf of the Italian Association


THER QUALMS?
D. Zerini of Radiation Oncology (AIRO) B. De Bari et al. Cancer
Radiotherapy Division, European Institute of Oncology, Treatment Reviews (50): 48–60, 2016.
2. Linee-Giuda AIRO 2016: Carcinoma della prostata.
Milan, Italy Antognoni P, Bertoni F, d’Angelillo RM, Jereczek-Fossa BA,
Magrini SM, Santoni R. Tumori 1 July 2016, special issue.
Aims: The aim of this presentation is to overcome 3. Stereotactic Body Radiotherapy for Low-and Intermediate-
the reluctance versus the implementation in the clinical Risk Prostate Cancer. Amar U. Kishan, MD, and Christopher
practice of extreme hypofractionation in primary R.King, MD, PhD. Semin RadiatOncol 27:268-278, 2017
prostate cancer radiotherapy, based on available radio- 4. Patient and Dosimetric Predictors of Genitourinary and
Bowel Quality of Life After Prostate SBRT: Secondary
biological, technical and clinical data. Analysis of a Multi-institutional Trial. Kyle Wang, MD,
Methods and Result: The obvious interest in extreme Ronald C. Chen, MD, MPH, Brent L. Kane, MD, Clinton A.
hypofractionation is based on the favorable radiobiolog- Medbery, MD Kelly J. Underhill, MD, James R. Gray, MD,
ical characteristics of prostate cancer and supported by Anuj V. Peddada, MD, and Donald B. Fuller, MD, Int J
Radiation Oncol Biol Phys, Vol. 102, No. 5: 1430-1437,
advantageous logistic, cost-benefit aspects deriving 2018
from short overall treatment time. The clinical validity 5. Patient-reported quality of life after stereotactic body radia-
of short-term treatment schedule is proven by a body of tion therapy versus moderate hypofractionation for clinically
non-randomized studies, using both isocentric (LINAC- localized prostate cancer. Skyler Bryce Johnson, Pamela R.
Soulos, Timothy D. Shafman, Constantine A. Mantz, Arie P.
based) or nonisocentric (CyberKnife-based) stereotactic Dosoretz, Rudi Ross, Steven E. Finkelstein, Sean P. Collins,
body irradiation techniques (SBRT). In a paper by De Simeng Suy, Jeffrey V. Brower, Mark A. Ritter, Christopher
Bari et al.1 twenty clinical studies, each enrolling more R. King, Patrick A. Kupelian, Eric M. Horwitz, Alan Pollack,
than 40 patients for a total of 1874 treated patients, were Matthew C. Abramowitz, Mark A. Hallman, Sergio Faria,
Cary P. Gross, James B. Yu. Radiotherapy and Oncology 12:
revised in terms of technological setting, toxicity, out- 294–298, 2016
come and quality of life assessment. The result of this 6. https://clinicaltrials.gov
review showed that as far as the rate of severe acute tox- 7. Stereotactic Body Radiotherapy for Primary Prostate Cancer.
icity is concerned, in all the available studies the treat- Kothari G, Loblaw A, Tree Alison C. et al. Technology in
Cancer Research & Treatment. Vol 17:1-13, 2018.
ment was globally well tolerated. While awaiting long- 8. Once-weekly versus every-other-day stereotactic body radio-
term data on efficacy and toxicity, the analyzed studies therapy in patients with prostate cancer (PATRIOT): A phase
suggest that the outcome profile of this approach, along- 2 randomizer trial. Quon HC, Ong A, Cheung P, et al.
side the patient convenience and reduced costs, is prom- Radiotherapy and Oncology 127: 206-212, 2018.
9. Stereotactic Body Radiation Therapy for Localized Prostate
ising. Forty-eight ongoing clinical trials are also present- Cancer: A Systematic Review and Meta-Analysis of Over
ed as a preview of the expectation from the near future. 6.000 Patients Treated on Prospective Studies. Int. J.
On this basis the Italian Association of Radiation Radiation Oncol. Biol. Phys, Vol 104 (4): 778-789, 2019.
Oncology endorsed the use of extreme hypofractiona-
tion inserting it as an option in the Prostate Cancer
Association Guidelines.2 Another review by Amar et al.3
supports the efficacy and safety of SBRT for PCa.
ANDROGEN DEPRIVATION THERAPY: ONLY IN

Dosimetric correlations with patient-reported urinary


UNFAVORABLE INTERMEDIATE RISK?
S. Fersino, V. Vanoni
and bowel quality of life were analyzed on a prospective
Radiotherapy Department, S.Chiara Hospital, Trento,
trial by Wang et al.4 Quality of life issues were also
Italy
reported in a paper by Johnson et al.5 showing that
patients who received SBRT or moderate hypofraction- Patients with intermediate-risk (IR) prostate cancer
ation have similar patient-reported change in bowel and (PC) are an heterogeneous group with highly variable
sexual symptoms, although there was worse change in prognosis. The classification system of National
urinary symptoms for patients receiving moderate Comprehensive Cancer Network (NCCN)1 stratifies
hypofractionation. At present thirteen studies on intermediate-risk patients into favorable and unfavor-
extreme hypofractionation are active at able according to clinical tumor stage (cT2b or cT2c),
ClinicalTrials.gov,6 encouraging update on two extreme grade group (2 or 3), PSA level and percentage of pos-
hypofractionation ongoing randomized trial itive biopsy. The combination of radiotherapy (RT) and
(Scandinavian HYPO-RT-PC and Canadian PATRIOT) androgen deprivation therapy (ADT) significantly

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reduced biochemical failure rates and improved overall-


and cancer-specific survival compared to RT alone.2
MOLECULAR AND RADIOMICS SIGNATURE AS

However, several investigators3,4 have shown that using


PREDICTIVE FACTORS OF TUMOR CONTROL

RT without ADT in men with favorable intermediate-


PROBABILITY (TCP)
E. D’Angelo
risk PC results in low rates of prostate cancer specific
mortality (PCSM) after 10 years (<2%); on the other UO Radioterapia, Azienda Ospedaliero Universitaria
hand, the addition of ADT to RT for unfavorable risk Policlinico di Modena On behalf of Head and Neck
group has been broadly accepted. EORTC 22991 trial working group of AIRO
showed that the addition of 6 months of ADT improved Head and neck cancers (HNSCC) represents a
biochemical disease free survival compared to RT alone unique model to apply the analysis of a large amount of
in IR patients.5 The RTOG 9910 randomised trial com- features in order to obtain predictive biomarker of
pared the efficacy of 4 months to 9 months of ADT and tumor control probability. The “older” analysis of sim-
demonstrated that there is no reason to extend ADT ple tumor size at imaging has moved recently into a
beyond 4 months in conjuction of ADT in men with IR deeper analysis of imaging and its finest characteristics
disease.6 Although several randomized trials have in the attempt to identify predictive biomarker of out-
shown that short term ADT improves overall survival come (radiomics). The routine use of computed tomog-
when added to RT, at least in the context of convention- raphy, magnetic resonance and often positron emission
al dose RT. This is not established for patients receiving tomography associated to its complex anatomy and het-
dose escalated RT.7 The RTOG 0815 ((NCT00936390) erogeneity of HNSCC, allows different approach in
is an ongoing trial in which men receive high-dose RT radiomics analysis. Sometimes and surprisingly, the
with or without 6 months of ADT. This study will pro- features extracted are exported in different cancer such
vide some evidence on whether 6 months of ADT evidenced by Aert1 biomarkers extracted from a lung
reduces PCSM in men with unfavorable IR PC under- cancer dataset and associated to oncological outcome,
going high-dose RT and whether high-dose RT alone is were translated and validated in independent datasets of
sufficient to minimize PCSM in men with favorable IR head and neck cancer patients. Many features often
PC. In conclusion, waiting ongoing trials within the IR emerged from the analysis, and it’s very difficult to
subgroups, withholding ADT in men with favorable IR understand real role and application of these plethora of
PC and adding 4 or 6 months of ADT to RT in men with data. An important contribute about this comes from
unfavorable IR PC are reasonable options based on the
Parmar’s studies2 the author tried to group in cluster the
available evidence.
imaging biomarkers from the vast amount of extracted
features and the results evidenced a significant associa-
References
tion with patient survival and tumor stage. Recently, the
1. National Comprehensive Cancer Network (NCCN) works of Leijenaar3 provide a proof of concept that a
Guidelines on Prostate Cancer 2019. radiomics analysis is able to derive molecular informa-
2. D'Amico AV, Chen MH, Renshaw AA, et al. Androgen sup-
pression and radiation vs radiation alone for prostate cancer: tion from standard medical images in HPV positive
a randomized trial. Jama. 2008;299(3):289–95. HNSCC patients: a “bridge” between different aspect.
3. Castle KO, Hoffman KE, Levy LB, et al: Is androgen depri- Another recent field of interest was the analysis of
vation therapy necessary in all intermediate-risk prostate
cancer patients treated in the dose escalation era? Int J Radiat molecular characteristics, in order to classified tumor
Oncol Biol Phys 85:693-699, 2013 not only and “simply” by histology, but also with the
4. Keane FK, Chen M-H, Zhang D, et al: The likelihood of goal of a major precision in our treatment. Gene expres-
death from prostate cancer in men with favorable or unfavor- sion profiles by microarrays or next-generation
able intermediate-risk disease. Cancer 120:1787-1793, 2014
5. Bolla M, Maingon P, Carrie C et al. Short Androgen sequencing platforms have been widely used in devel-
Suppression and Radiation Dose Escalation for Intermediate- oping biomarkers in HNSCC. These gene expression
and High-RiskLocalized Prostate Cancer: Results of EORTC subtypes were correlated with biological features of
Trial 22991. J Clin Oncol. 2016 May 20;34(15):1748-56. tumors as well as the clinical outcome of patients.
6. Pisansky TM, Hunt D, Gomella LG et al. Duration of andro-
gen suppression before radiotherapy for localized prostate Linge4 et al. reported that high expression levels of
cancer: radiation therapy oncology group randomized clini- hypoxia-induced gene signature and cancer stem cell
cal trial 9910. J Clin Oncol. 2015 Feb 1;33(4):332-9. markers were correlated with poor prognosis after post-
7. Showalter TN. In search of answers regarding the benefits
and harms of short term ADT for intermediate-risk prostate operative chemoradiotherapy in HNSCC patients;
cancer. Can J Urol. 2017 Feb;24(1):8663. another5 showed that the molecular profile of recurrent
and metastatic tumors is quite distinct from primary
tumors. However, most of these gene signatures were
reported as prognostic factors for HNSCC. Little bio-
markers have been developed for predicting the clinical
benefit of treatment. The molecular and radiomics data
today at our disposal are probably the way of future to
improve the prediction on outcome. However the great
variability and the lack of validation of various model
used and the big amount of features potentially extract-
ed, represent actually the real limit of this approach.
Standardization of procedure and a rigorous quality

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

approach probably allows us to identified more limited usually based on dose–volume histograms, which are
but also reproducible features. not ideal representations of 3-dimensional doses and
assume that all the regions of an OAR have an equal
References functional importance, thus discarding organ specific
1. Aerts HJ, Velazquez ER, Leijenaar RT, et al. Decoding spatial Information. Moreover, they do not take into
tumour phenotype by noninvasive imaging using a quantita- account fraction dose variations, nor anatomical varia-
tive radiomics approach. Nat Commun 2014;5:4006. tions of the OAR and its dosimetric consequences dur-
2. Parmar C, Leijenaar RT, Grossmann P, et al. Radiomic fea- ing treatment. Models taking into account more data
ture clusters and prognostic signatures specific for Lung and
Head & Neck cancer. Sci Rep 2015;5:11044 such as 3-dimensional dose distribution in OARs,
3. Leijenaar RTH, Bogowicz M, Jochems A, Hoebers FJP, dependencies between the dose delivered at other
Wesseling FWR, Huang SH, et al. Development and valida- OARs may enhance toxicity prediction. Dose-volume
tion of a radiomic signature to predict HPV (p16) status from histograms of the whole organ at risk (that treat the
standard CT imaging: a multicenter study. Br J Radiol 2018;
91: 2017049811075 organ as a homogeneous entity) are not a suitable basis
4. Linge A, Lock S, Gudziol V, Nowak A, Lohaus F, von for biology-based NTCP models. Depending on the
Neubeck C, Jütz M, Abdollahi A, Debus J, Tinhofer I, et al: normal tissue complication which is taken as the most
Low Cancer Stem Cell Marker Expression and Low Hypoxia critical and needs to be avoided as much as possible,
Identify Good Prognosis Subgroups in HPV(−) HNSCC after
Postoperative Radiochemotherapy: A Multicenter Study of different structures or sub-volumes of the respective
the DKTK-ROG. Clin Cancer Res. 22:2639–2649. 2016 critical organ/s at risk have to be delineated.4
5. Morris LGT, Chandramohan R, West L, et al. The Molecular In the next future, the adoption of molecular and
Landscape of Recurrent and Metastatic Head and Neck Radiomic signatures could improve the NTCP as accu-
Cancers: Insights From a Precision Oncology Sequencing
Platform. JAMA Oncol. 2017;3(2):244–255. rate predictive factors in a new era of personalized med-
doi:10.1001/jamaoncol.2016.1790 icine for head and neck cancer.

References
1. Rubin P, Cassarett G W, 1972. A direction for clinical radiation
pathology. In:Vaeth, JM et al, eds. Frontiers of radiation ther-
MOLECULAR AND RADIOMIC SIGNATURES AS
apy and oncology VI. Baltimore: University Park Press. pp.
NTCP PREDICTIVE FACTORS
R. Mazzola 1-16
Advanced Radiation Oncology Department, IRCCS, 2. https://icru.org/home/reports/fundamental-quantities-and-
units-for-ionizing-radiation-report-60
Sacro Cuore Don Calabria Negrar-Verona, Italy 3. Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine
LS, Eisbruch A, et al. Use of normal tissue complication
From 1970s, several conceptual revolutions were probability models in the clinic. Int J Radiat Oncol Biol Phys.
made in the field of normal tissue complication proba- 2010 Mar 1;76(3 Suppl):S10-9. doi: 10.1016/
bility (NTCP). Firstly, Rubin and Cassarett introduced j.ijrobp.2009.07.1754.
4. Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine
the concepts of TD5/5 (i.e. the probability of 5% com- LS, Eisbruch A, et al. Use of normal tissue complication
plication within 5-years from treatment) and TD50/5 probability models in the clinic. Int J Radiat Oncol. (2010)
(the probability of 50% complication within 5-years).1 76:S10–9
At the beginning of 1990, the Lyman-Kutcher Burman
model was the most commonly used tool to assess
NTCP. In the same year, the International Commission
on Radiological Protection has proposed the concept of
NANOPARTICLES AND RADIOSENSITIZATION:

organ at risk dose constraint (60 ICRU).2 After 20


BIOLOGICAL BASIS
M. Loi
years, the publication of the Quantitative Analysis of
Normal Tissue Effects – QUANTEC – has changed the Radiotherapy Department Università degli studi di
daily clinical practice of Radiation Oncologists.3 Firenze, Italy
Recently, the Innovation in medical imaging has led The broad spectrum of properties of nanomaterials
to a dramatic increase of resolution and imaging modal- may provides a wide range of biomedical applications.
ities, reproducible protocols, and image analysis such as In radiation oncology, the main goal is to raise the ther-
Radiomic. It consists in extracting hundreds of quanti- apeutic efficacy of ionizing radiations without addition-
tative features by an automated or semi-automated soft- al damage to the surrounding structures, thus increasing
ware. Radiomic relies on the hypothesis that mineable the differential effect between healthy and tumor tis-
data can be extracted from medical images and provide sues. Nanoparticles (NPs), in particular high atomic-
additional information on gene protein and tumor phe- number (z) NPs, have been studied in the preclinical
notype and then used for patient care. The real question setting, showing a radio-sensitizing activity that exceed
could be: are we ready to adopt Radiogenomic in daily mere expected physical interaction and may underlie
clinical practice? Probably no. There is an acute need complex biological mechanisms of synergy such as
for rigorous evaluation criteria and reporting guidelines increased ROS generation, cell cycle alteration, vascu-
which will allow establishing Radiogenomics as a firm lar damage and, as more recently highlighted, modula-
scientific discipline in Radiation Oncology. On the tion of the immune response. Advances in nanotechnol-
other hand, there is the need to improve the NTCP accu- ogy manufacturing allow to increase the versatility of
racy for the benefit of head and neck cancer patients. In NPs by transferring new properties in order to enhance
fact, NTCP has several limitations. NTCP models are tumor selectivity, such as molecular targeting through

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Programme

chemical coating, or to favor association with other normal tissue toxicity and accurate radiation dose deliv-
radiosensitizing agents such as hyperthermia, for ery may affect the efficacy of RT. Nanotechnology has
exemple by employing magnetic NPs. Despite encour- also emerged as a promising strategy and offers a num-
aging pioneering trials and initial approval of NPs in ber of unique features suited for applications in RO.
association with radiotherapy in specific patient sub- Nanoparticles can be programmed to preferentially
sets, crucial criteria such as desirable physicochemical release therapeutic agents to tumor cells, owing to
properties, route of administration, dosing and irradia- enhanced permeability and drug retention effect, hence
tion schedule still need to be defined in order to maxi- a gain in safety and effectiveness from combination
mize the benefits of NPs in clinical practice. therapy. The preferential accumulation of nanoparticles
in the tumor cells may lead to: (a) improved contrast
References enhancement for image-guided RT (IGRT); (b) tumor-
Kunjachan S, Detappe A, Kumar R, Ireland T, Cameron L, specific delivery of chemotherapeutic agents or target
Biancur DE, Motto-Ros V, Sancey L, Sridhar S, therapies in combination with ionizing radiation; (c)
Makrigiorgos GM, Berbeco RI. Nanoparticle Mediated increased local radiation dose using particles with high
Tumor Vascular Disruption: A Novel Strategy in Radiation atomic numbers. Different nano-platforms have been
Therapy. Nano Lett. 2015 Nov 11;15(11):7488-96.
Cui L, Her S, Borst GR, Bristow RG, Jaffray DA, Allen C. investigated for radiotherapeutic applications. Among
Radiosensitization by gold nanoparticles: Will they ever them, gold nanoparticles were very promising due to
make it to the clinic? Radiother Oncol. 2017 Sep;124(3):344- their high X-ray absorption coefficient and the ease of
356. their synthetic manipulation. The role of the emerging
Rosa S, Connolly C, Schettino G, Butterworth KT, Prise KM.
Biological mechanisms of gold nanoparticle radiosensitiza- gold nanoparticles aided radiotherapy modalities was
tion. Cancer Nanotechnol. 2017;8(1):2. doi: 10.1186/s12645- explored in this overview of the available clinical trials,
017-0026-0. with the aim to assess their establishment as more effec-
Butterworth KT, McMahon SJ, Currell FJ, Prise KM. Physical tive RT treatment options than the actual standard of
basis and biological mechanisms of gold nanoparticle
radiosensitization. Nanoscale. 2012 Aug 21;4(16):4830-8. care for cancer patients.
doi: 10.1039/c2nr31227a
Retif P, Pinel S, Toussaint M, Frochot C, Chouikrat R, Bastogne
T, Barberi-Heyob M. Nanoparticles for Radiation Therapy
Enhancement: the Key Parameters. Theranostics. 2015 Jun MOLECULAR BIOLOGY AND MULTIDISCIPLINARY
11;5(9):1030-44. doi: 10.7150/thno.11642. eCollection 2015
Bonvalot S, Rutkowski PL, Thariat J, Carrère S, Ducassou A,
TREATMENT OF PEDIATRIC BRAIN TUMORS
Sunyach MP, Agoston P, Hong A, Mervoyer A, Rastrelli M, M. Massimino
Moreno V, Li RK, Tiangco B, Herraez AC, Gronchi A, Fondazione IRCCS Istituto Nazionale dei Tumori,
Mangel L, Sy-Ortin T, Hohenberger P, de Baère T, Le Cesne Milano, Italy
A, Helfre S, Saada-Bouzid E, Borkowska A, Anghel R, Co A,
Gebhart M, Kantor G, Montero A, Loong HH, Vergés R, Background: The 2016 edition of the World Health
Lapeire L, Dema S, Kacso G, Austen L, Moureau-Zabotto L,
Servois V, Wardelmann E, Terrier P, Lazar AJ, Bovée JVMG, Organization Classification of Tumors of the Central
Le Péchoux C, Papai Z. NBTXR3, a first-in-class radioen- Nervous System utilizes integrated diagnosis incorpo-
hancer hafnium oxide nanoparticle, plus radiotherapy versus rating both morphologic and molecular features.
radiotherapy alone in patients with locally advanced soft-tis- Despite tremendous successes in understanding their
sue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, ran-
domised, controlled trial. Lancet Oncol. 2019 Jul 8. pii: biology in the last decade, brain tumours remain the
S1470-2045(19)30326-2. highest cause of mortality and morbidity rates in child-
Spirou SV, Costa Lima SA, Bouziotis P, Vranješ-Djurić S, hood and adolescence.
Efthimiadou EΚ, Laurenzana A, Barbosa AI, Garcia-Alonso Methods: In the field of pediatric neuro-oncology
I, Jones C, Jankovic D, Gobbo OL. Recommendations for In
Vitro and In Vivo Testing of Magnetic Nanoparticle this has meant a great deal of diagnostic changes espe-
Hyperthermia Combined with Radiation Therapy. cially for medulloblastoma, other embryonal tumors
Nanomaterials (Basel). 2018 May 6;8(5). pii: E306. doi: and high-grade glioma patients but the impact on thera-
10.3390/nano8050306 peutic decision is a modulation between still important
clinical features of patients at different ages and these
new acquirements.
PRELIMINARY RESULTS AND FUTURE Results: Some entities, now more precisely molec-
ularly such as diffuse midline gliomas with histone
H3.3 mutations and embryonal tumours with multi-lay-
DIRECTIONS IN THE USE OF NANOPARTICLES

ered rosettes (ETMR), plus molecularly defined subsets


IN COMBINATION WITH RADIOTHERAPY

of hemispheric high-grade gliomas, medulloblastomas


AND SYSTEMIC THERAPIES
L. Triggiani
and atypical teratoid/rhabdoid tumours, are still associ-
Radiation Oncology Department, Brescia University,
ated with a universally fatal outcome to date. Other
Brescia, Italy
entities achieve a better cure rate but with severe late
Radiation Oncology (RO) is constantly evolving effects of disease and treatments and also require
thanks to progress in radiobiological knowledge, but improvements of current treatments. We can only be
also advances in treatment options and dose delivery successful in paediatric neuro-oncology when taking a
techniques. However, the latter do not necessarily result multi-disciplinary approach – ranging from preclinical
in a significant change in cure rates for radiotherapy teams through to all involved specialized clinical disci-
(RT), since multiple variables like tumor resistance, plines. These need to address the definition of “preclin-

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

ical evidence”, understanding of the special microenvi-


ronment in the brain and its clinical implications, defi-
THE BEST TECHNOLOGY FOR PHOTON BASED

nition of sampling and molecular diagnostics standards


RADIOTHERAPY
S. Scoccianti, M.A. Teriaca, V. Lorenzetti, C. bellini,
(including advanced biomarkers such as liquid biop- G. Caramia, L. Livi
sies), standards of advanced neuroimaging, neurologi-
cal/neuropsychological trial endpoints, local delivery Radioterapia Oncologica, Azienda Ospedaliera
trials, radio-sensitizing trials, advanced supportive care, Universitaria Careggi, Firenze, Italy
trials in the context of neurodevelopment/neurocogni- Radiotherapy plays a fundamental role in the cure
tive late effects and autopsy programs to benefit the of pediatric brain cancer. It is frequently employed
next generation of patients, etc. exclusively or as part of a multimodality treatment
Conclusions: An improved understanding of the approach in combination with surgery and/or che-
molecular genetics, epigenetics, and cellular biology motherapy. Radiotherapy plays a fundamental role in
underpinning childhood brain tumours will potentially the management of pediatric cancer, with the primary
enable more effective and less toxic treatment strategies aim of achieving a high therapeutic ratio (the highest
to be developed and implemented. This could spare probability of cure with the lowest risk of toxicity).
children from the severely detrimental consequences Considering the risk of severe late effects (mainly,
associated with conventional treatment protocols and neurocognitive deficits, hearing loss and hormonal defi-
improve the outlook for patients with currently incur- ciency for impairment of hypothalamic-pituitary axis) ,
able disease a major goal of pediatric cancer radiotherapy is to main-
tain or improve cancer cure rates, while decreasing
References treatment sequelae. In addition the risk of second mali-
1. Louis DN, Perry A, Reifenberger G, von Deimling A, gnancy years after treatment may develop. Notably, the
Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, late effects of cranial irradiation are affected by a num-
Kleihues P, Ellison DW. The 2016 World Health ber of critical factors, including total and fractional
Organization Classification of Tumors of the Central
Nervous System: a summary. Acta Neuropathol. 2016 dose, dose to organs at risk, use of other treatment
Jun;131(6):803-20. modalities (chemotherapy and surgery), use of other
2. Massimino M, Biassoni V, Gandola L, Garrè ML, Gatta G, drugs (steroids and antiepilectic drugs) and patient age
Giangaspero F, Poggi G, Rutkowski S. Childhood medul-
loblastoma. Crit Rev Oncol Hematol. 2016 Sep;105:35-51 during brain irradiation.
3. Pollack IF, Agnihotri S, Broniscer A. Childhood brain A variety of very conformal radiation therapy tech-
tumors: current management, biological insights, and future niques with photons have been developed to try to limit
directions. J Neurosurg Pediatr. 2019 Mar 1;23(3):261-273. the high radiation dose region to the tumor target. Fixed
4. Rutkowski S, Modena P, Williamson D, Kerl K, Nysom K,
Pizer B, Bartels U, Puget S, Doz F, Michalski A, von Hoff K, beams IMRT, Volumetric Modulated Arc Therapy
Chevignard M, Avula S, Murray MJ, Schönberger S, Czech (VMAT) and Tomotherapy are the most promising tech-
T, Schouten-van Meeteren AYN, Kordes U, Kramm CM, van niques. The superiority of IMRT over conventional
Vuurden DG, Hulleman E, Janssens GO, Solanki GA, van photon radiotherapy in terms of conformality and dose
Veelen MC, Thomale U, Schuhmann MU, Jones C,
Giangaspero F, Figarella-Branger D, Pietsch T, Clifford SC, homogeneity was reported from dosimetric studies
Pfister SM, Van Gool SW. Biological material collection to addressing different tumour sites. With these treatment
advance translational research and treatment of children with modalities, new organs at risk (hypothalamus, pituitary,
CNS tumours: position paper from the SIOPE Brain Tumour
Group. Lancet Oncol. 2018 Aug;19(8):e419-e428. hippocampus, scalp..) beyond the“classical” ones may
5. Jones DTW, Kieran MW, Bouffet E, Alexandrescu S, be spared.
Bandopadhayay P, Bornhorst M, Ellison D, Fangusaro J, In addition, the advantages in terms of conformality
Fisher MJ, Foreman N, Fouladi M, Hargrave D, Hawkins C, of modern techniques make reirradiation a reliable
Jabado N, Massimino M, Mueller S, Perilongo G, Schouten
van Meeteren AYN, Tabori U, Warren K, Waanders AJ, option for recurrent pediatric brain tumors. By contrast,
Walker D, Weiss W, Witt O, Wright K, Zhu Y, Bowers DC, the possibility of sparing critical structures may be
Pfister SM, Packer RJ. Pediatric low-grade gliomas: next achieved with these techniques at the cost of increasing
biologically driven steps. Neuro Oncol. 2018 Jan the low doses-bath with a potential risk of secondary
22;20(2):160-173.
6. Merchant TE. Current Clinical Challenges in Childhood carcinogenesis.
Ependymoma: A Focused Review. J Clin Oncol. 2017 Jul Deep understanding of individual risk factors, nor-
20;35(21):2364-2369. mal tissues anatomy, functional brain regions and dose
constraints has to be gained in order to take maximal
benefit from technical solutions. Prospective trials that
monitor the late effects from “modern” photons treat-
ment (as well as protons treatments) would be needed to
confirm the expected reduction in long-term side
effects. In addition, the collection of large data in mul-
tiinstitutional registries can help in improving eviden-
ces in terms of outcome of different technologies.

References
1. Schwartz CL. Long-term survivors of childhood cancer: the
late effects of therapy. The Oncologist 1999;4:45-54.

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2. Halperin EC, Constine LS, Tarbell NJ et al., eds. Pediatric stratification and verifying which of these may receive
Radiation Oncology, Third Edition. Philadelphia: Lippincott a lower dose. Careful follow-up, quality controls will be
Williams & Wilkins, 1999:1-586.
3. Kirsch D, Tarbell NJ. Conformal radiation therapy for child- necessary to assess whether advanced techniques can
hood CNS tumors. The Oncologist 2004;9; 442-450 reduce late side effects and only then will it be possible
4. Paulino AC. Treatment strategies to reduce radiotherapy late to assess whether the RT with protons is higher.
effects in children. J Radiat Oncol 2013;2:121-128.
References
5. Steinmeier T et al. Evolving techniques in paediatric oncolo-
gy. Clin Onc 2019; 142-150.
6. Merchant et al. Late Effects of Conformal Radiation Therapy 1. Greenfield, B.J.; Okcu, M.F.; Baxter, P.A.; Chintagumpala,
for Pediatric Patients With Low-Grade Glioma: Prospective M.; Teh, B.S.; Dauser, R.C.; Su, J.; Desai, S.S.; Paulino, A.C.
Evaluation of Cognitive, Endocrine, and Hearing Deficits. J Long-term disease control and toxicity outcomes following
Clin Onc 27:3691-3697 surgery and intensity modulated radiation therapy (IMRT) in
pediatric craniopharyngioma. Radiother. Oncol. J. Eur. Soc.
Ther. Radiol. Oncol 2015, 114, 224–229
2. Nanda, R.H.; Ganju, R.G.; Schreibmann, E.; Chen, Z.;
Zhang, C.; Jegadeesh, N.; Cassidy, R.; Deng, C.; Eaton, B.R.;
PHOTONIC RADIOTHERAPY. ADVANTAGES AND
Esiashvili, N. Correlation of Acute and Late Brainstem
DISADVANTAGES IN PAEDIATRIC ONCOLOGY
S. Barra Toxicities With Dose-Volume Data for Pediatric Patients
Radioterapia infantile, Policlinico San Martino, With Posterior Fossa Malignancies. Int. J. Radiat. Oncol.
Biol. Phys. 2017, 98, 360–366
Genova, Italy 3. Bhakta N., Qi Liu, K Ness K, Baassiri M, Eissa H, Yeo F,
Chemaitilly W, J Ehrhardt M, Bass J, W Bishop M, Shelton
Radiation therapy is an important component of the K, Lu Lu, HuangS, Li Z, Caron E, Lanctot J, Howell C, Folse
multimodal approach to cancer treatment. Continual, T, Joshi V, l M Green D, A Mulrooney D, T Armstrong G, R
significant improvement has occurred in both photon Krull K, M Brinkman T, B Khan R, K Srivastava D, M
and proton radiation therapy, with more precise dose Hudson M, Yasui Y, L Robison L . The cumulative burden of
surviving childhood cancer: an initial report from the St Jude
conformity reduce radiation of adjacent normal tissues Lifetime Cohort Study (SJLIFE). Lancet 2017; 390: 2569–82
and associated risks. Late toxicities are most important 4. Iska Moxon-Emre, Eric Bouffet, Michael D. Taylor,
in children and include diminished cognition, growth Normand Laperriere, Nadia Scantlebury, Nicole Law, Brenda
delay, bone deformation, endocrine dysfunction, and J. Spiegler, David Malkin, Laura Janzen, and Donald
Mabbott. Impact of craniospinal dose, boost volume, and
second malignancies. This superior dosimetry can neurologic complications on Intellectual outcome in patients
translate into clinical benefit with respect to the end- wth Medulloblastoma. J Clin Oncol 2014 32:1760-1768.
points of toxicity, tumour control, quality of life, and 5. Barra S, Gusinu M, Timon G, Giannelli F1, Vidano G, Garrè
patient survival. intensity-modulated RT(IMRT) has ML, Corvò R.Pediatric craniospinal irradiation with conven-
tional technique or helical tomotherapy: impact of age and
entered mainstream clinical practice and use, including body volume on integral dose. Tumori. 2016 Aug
among paediatric neuro-oncology patients. IMRT has 3;102(4):387-92.
been shown to improve target conformity as well as 6. Murphy, M.J, Balter, J. Balter, S. BenComo, J.A., Jr.; Das,
critical structure sparing when compared to standard I.J.; Jiang, S.B.; Ma, C.M.; Olivera, G.H.; Rodebaugh, R.F.;
Ruchala, K.J.; et al. The management of imaging dose during
3D-CRT approaches.1,2 These dosimetric advantages to image-guided radiotherapy: Report of the AAPM Task
IMRT are supported by clinical data, which demon- Group 75. Med. Phys. 2007, 34, 4041–4063.
strate comparable rates of disease control with IMRT 7. Clayton B. Hess, Holly M. Thompson, MD, MPH, Stanley
approaches but decreased RT-related toxicity, particu- H. Benedict, J. Anthony Seibert, PhD, Kenneth Wong,
Andrew T. Vaughan, and Allen M. Chen, Exposure Risks
larly: ototoxicity, endocrine dysfunction and cognitive Among Children Undergoing Radiation Therapy:
damage. Expanding on IMRT, arc-based therapies have Considerations in the Era of Image Guided Radiation
increasingly been utilized. An advantage of VAMAT Therapy. Int J Radiation Oncol Biol Phys, 2016;94, 5: 978-
(Volumetric-modulated arc therapy), in addition to the 992.
excellent compliance of the dose and the use of non-
coplanar planes, is the speed of treatment delivery. This
difference is particularly advantageous for paediatric
patients, whose tolerance for treatments may be more
THE APPROPRIATE CHOICE BETWEEN PHOTON

limited than adult patients, and many of whom may


AND PROTON THERAPY: COMPARATIVE EXPERI-

require sedation while undergoing treatment. But this


ENCES
F. Valvo
improvement can come at a cost of greater radiation Centro Nazionale di Adroterapia Oncologica, Pavia,
exposure to non-targeted tissues when compared to less Italy
sophisticated techniques. An important assessment is
the low-dose bath that these techniques may involve5 Brain tumours are the most frequent solid tumours
and the daily use of IGRTs. With doses of approximate- in children. Late effects of paediatric cerebral radiation
ly 3 cGy per CBCT has the potential to substantially therapy, cognitive dysfunction and endocrinopathy are
increase risk of late effects.6,7 Advanced radiotherapy the most frequent side effects of brain radiation therapy.
techniques have enabled volumes to be reduced with Depending on tumour location; auditive and visual
high doses, improving the reproducibility of the treat- impairment are also frequent. These late effects mani-
ment. It will be necessary to correct these technological fest in a multitude of presentations including impair-
advantages with prospective studies designed to reduce ment of neurocognitive development, hormonal dys-
field size and the total dose. Currently many studies, on function secondary to hypothalamic-pituitary axis radi-
biological data, are studying a more accurately patient ation with resultant growth or gonadal dysfunction, as

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

well increased risk of secondary malignancies. In an


attempt to reduce unnecessary radiation dose to organs
RADIOMIC FOR PCR AND OUTCOMES

at risk for late effects, there has been a strong move-


PREDICTION IN RECTAL CANCER
M.A. Gambacorta1,2, L. Boldrini1,2, G. Chiloiro1,2,
ment to utilize increasingly conformal modes of radia- E. Meldolesi1
tion therapy. Compared to photon therapy, PRT has a 1Fondazione Policlinico Universitario “A. Gemelli”
region of high dose deposition, with minimal dose
delivery distal to the region of the Bragg Peak. This is IRCCS, Roma; 2Istituto di Radiologia, Università
in stark contrast to photons, which enter with high ener- Cattolica del Sacro Cuore, Roma, Italy
gies and deposit their dose not only throughout the Rectal cancer treatment is a multistep approach
tumor but also distal to the target As such, PRT allows requiring a multi-specialists’ cooperation. In particular,
significant reduction of the overall integral dose a child Locally Advanced Rectal Cancer is usually treated with
receives, potentially reducing risk of late side effects of preoperative chemoradiation followed by surgery with
such a dose “bath”. With the advent of improved treat- or without postoperative chemotherapy according to
ment modalities, our goal for treating pediatric malig- risk factors related to initial staging and pathological
nancies should be not only to increase survival rates, tumor response. Oncological outcomes and response to
but also quality of life for these survivors. PRT is an preoperative treatment have a wide range of presenta-
important modality that can help achieve such a pro- tions and several factors need usually to be combined to
found goal. The utilization of PRT has been considered predict tumor response and outcomes. Among these
since as early as the 2000’s for the most common child- factors, information coming from imaging play a funda-
hood CNS malignancies. It has maintained continued mental role as predictors, also allowing adaptation of
interest because it not only shows comparable clinical therapies throughout the treatment path of the patient.
outcomes to photon therapy but also the dosimetric In this frame, Magnetic Resonance Imaging (MRI) has
advantage of reducing dose to unintentionally irradiated proven to be effective for rectal cancer staging and
tissues.The literature analysis is in favour of the use of prognostic evaluation with the use of qualitative and
proton therapy for paediatric brain tumour in a curative functional information (e.g. DWI). Radiomics is a
intent, either for focal irradiation, whole ventricular new-born science that aims to extract large amount of
irradiation, or craniospinal irradiation. In addition of the quantitative features from medical images. These fea-
survival literature data is in favour of neurocognitive, tures have the potential to disclose disease characteris-
sensorial and endocrine benefits with protons compared tics impossible to be appreciated by the human eye,
to photons for all paediatric patients treated for brain useful for predicting prognosis and therapeutic response
tumours in a curative intend. of tumors. The process of radiomic consists in 4 phases:
The analyses showed that this achievement was image acquisition, image segmentation, features extrac-
mainly obtained through the reduction of late toxicity. tion and quantification, analysis and modelling. Recent
Actually, reductions in intelligence quotient loss and experiences of radiomics in rectal cancer tested the fea-
growth hormone deficiency contributed to the greatest sibility of setting up predictive models of several clini-
part of the cost savings and were the most important cal outcomes (e.g. pathological complete response -
parameters for cost-effectiveness. Many ongoing pCR, Overall Survival - OS, Metastases Free Survival -
prospective clinical trials will allow evaluating the effi- MFS). Main goal of this talk is to present the meaning
cacy and toxicity of protontherapy. With increasing and the process of radiomics, giving an overview about
medical imaging tumour evaluation, one can also sug- the existing radiomics models for outcome prediction in
gest that protontherapy could be also used for dose- patients affected by rectal cancer and discussing their
escalation on resistant tumours (radioresistant clusters role in supporting the choice of treatments that could be
identified by molecular imaging) without increased tailored to tumor phenotype, as coded by the radiomics
healthy tissue irradiation. The centers of protonthera- analysis, and that can be used as an additional tool to
py with children-dedicated equipment are needed to identify patients eligible for an organ-preserving treat-
offer equal access to this therapy. These centres should ment. Different models will be presented, focusing both
include general anaesthesia capacity, trained team and on long terms outcomes and pCR prediction, on staging
could be cost-efficient. MRI and radiomics values change during treatment
(delta radiomics) with hybrid Magnetic Resonance
References guided Radiotherapy (MRgRT) machines.
1. Schwartz CL. Long-term survivors of childhood cancer: the
late effects of therapy. Oncologist 1999;4:45-54. References
2. Mizumoto M, Oshiro Y, Takizawa D, et al. Proton beam ther-
apy for pediatric ependymoma. Pediatr Int 2015;57:567-71. 1. D. Cusumano, N. Dinapoli, L. Boldrini et al. “Fractal-based
3. Macdonald SM, Sethi R, Lavally B, et al. Proton radiothera- radiomic approach to predict complete pathological response
py for pediatric central nervous system ependymoma: clini- after chemo-radiotherapy in rectal cancer” Radiol Med.
cal outcomes for 70 patients. Neuro Oncol 2013;15:1552-9. 2018 Apr;123(4):286-295. doi: 10.1007/s11547-017-0838-3.
4. Armstrong FD. Proton-beam radiation therapy and health- 2. N. Dinapoli, B. Barbaro, R. Gatta et al. “Magnetic
related quality of life in children with CNS tumors. J Clin Resonance, vendor-independent, intensity histogram analysis
Oncol 2012;30:2028-9. predicting pathological complete response after
radiochemotherapy of rectal cancer” International Journal of
Radiation Oncology, Biology, Physics – 2018 May 4. pii:
S0360-3016(18)30743-0.
3. L. Boldrini, D. Cusumano, G. Chiloiro et al. “Delta

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Programme

Radiomics for rectal cancer response prediction with hybrid achieving a complete response. Currently, guidelines
0.35 T Magnetic Resonance guided Radiotherapy (MRgRT) recommend low dose PCI, typically 25 Gray in 10 daily
: a hypothesis generating study for an innovative personal-
ized medicine approach” Radiol Med. 2019 Feb;124(2):145- fractions in order to minimize late sequelae in long-
153. doi: 10.1007/s11547-018-0951-y. term survivors. The subsets of high risk patients such as
the elderly3 and patients who have been exposed to cis-
platin4 could develop significant brain radiation injury
despite the conservative radiation prescriptions.
Whether or not reduction of exposure of structures such
THORACIC RADIOTHERAPY IN SCLC: STATE OF

as the hippocampus, applying modern technologies in


THE ART AND INTEGRATED TREATMENTS IN THE
meaningful benefit to patients, is the subject of ongoing
EXTENDED DISEASE
P. Borghetti, A. Guerini, M. Maddalo trials. To date the PCI seems to be favorable in terms of
Radiation Oncology Department, ASST -Spedali Civili local control and overall survival in limited stage small
and University of Brescia, Italy cell lung cancer patients aged < 65 years and with low
Background: The standard of treatment for patients T stage. Conversely, the therapy no significantly ame-
with stage IV SCLC consists of four to six cycles of pal- liorates the overall survival in patients aged ≥65 years
liative chemotherapy (platinum/etoposide). There is with cT3–4 disease and/or females gender.5 The benefit
still no clear consensus concerning the role of consol- of PCI in patients with extensive stage disease is con-
idative thoracic radiotherapy (TRT) in this setting. troversial even after a complete response to chemother-
Methods: We performed a review of the current lit- apy.6,7 There are evidences that the risk of intracranial
erature regarding TRT in the treatment of stage IV relapse has likely been overestimated in the past and the
SCLC, with particular emphasis on the analysis of sur- efficacy of contemporary salvage treatments for
vival, response rate and disease control results and on intracranial relapse may be underestimated especially if
the influence of multiple risk factors. provided before patients become symptomatic. The
Results: Although phase III CREST trial primary most recent guidelines recommend that only patients
endpoint of OS improvement at 1 year was not met, who have responded to systemic treatment should be
subgroups analysis revealed an OS benefit in selected considered for PCI that should be administered only
patients such as those with residual disease after after the completion of all of the planned induction
chemotherapy, limited extrathoracic disease burden and chemotherapy. PCI should be offered to patients in
good response after chemotherapy. Other prospective whom asymptomatic small volume brain metastases
and retrospective studies also showed benefit in local have recently been excluded by volumetric MR imag-
control and survival. Several factors might be consid- ing. The role of sparing hippocampus techniques to
ered to recommend TRT: fitness of the patient, extratho- attempt to reduce neurological toxicities without a neg-
racic tumour burden, initial bulky thoracic disease and ative impact on local control is under investigation.
response to chemotherapy.
Conclusions: Albeit to date there is no consensus References
for the indications of TRT in stage IV SCLC, it should 1. Hansen HH. Should initial treatment of small cell carcinoma
be considered for fit patients who responded to include systemic chemotherapy and brain irradiation? Cancer
Chem Rep 1973;4(2):239–41
chemotherapy and bear limited residual extrathoracic 2. Auperin A, Arriagada R, Pignon JP, Le Pechoux C, Gregor A,
tumor burden. Stephens RJ, et al.Prophylactic cranial irradiation for patients
with small-cell lung cancer in com-plete remission.
Prophylactic cranial irradiation overview collaborative
group.N Engl J Med 1999;341:476–84.
PROPHYLACTIC CRANIAL IRRADIATION IN SCLC 3. Grau JJ, Verger Brandes AA, Rigon A, Monfardini S,
DeAngelis LM. Radiotherapyof the brain in elderly patients.
Eur J Cancer 2000; 36:443–52.
IN 2019: “MILESTONE” OR OUTDATED
4. Lowe WK, Toh ST, Wee J, Fook-Chong S, Wand DY.
THERAPEUTIC OPTION?
G. Iatì Sensorineural hearing lossafter radiotherapy and chemother-
apy: a single blinded randomized study. JClin Oncol
Operative Unit of Oncological Radiotherapy, 2006;24(12):1904–9.
University of Messina, Italy 5. Kim TG, Pyo H, Ahn YC, Noh JM, Oh D. Role of prophy-
lactic cranial irradiation for elderly patients with limited-dis-
The original rationale for prophylactic cranial irra- ease small-cell lung cancer: inverse probability of treatment
diation (PCI), as advocated by Hansen1 in 1973, is that weighting using propensity score. J Radiat Res. 2019 Jun 5.
CNS relapse in small cell lung cancer is analogous to pii: rrz040. doi: 10.1093/jrr/rrz040. [Epub ahead of print]
PubMed PMID: 31165148.
isolated CNS relapse in acute lymphoblastic leukaemia. 6. Nosaki K, Seto T, Shimokawa M, Takahashi T, Yamamoto N.
The brain, in fact, was assumed to be a pharmacologic Is prophylactic cranial irradiation (PCI) needed in patients
sanctuary where subclinical metastases were protected with extensive-stage small cell lung cancer showing com-
from cytotoxic drugs by the blood–brain barrier, and it plete response to first-line chemotherapy? Radiother Oncol.
2018 Jun;127(3):344-348.
was suggested that cranial irradiation might prevent the 7. Ge W, Xu H, Yan Y, Cao D. The effects of prophylactic cra-
development of clinically evident brain metastases. nial irradiation versus control on survival of patients with
Since then PCI had become the standard of care for extensive-stage small-cell lung cancer: a meta-analysis of 14
many patients treated for small cell lung cancer. The trials. Radiat Oncol. 2018 Aug 23;13(1):155.
first meta-analysis supporting its use was published in
19993 particularly in patients with limited stage disease

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

molecular genetic basis of EC development and defined


four molecular subclasses, based on mutation burden and
OPEN QUESTIONS IN THE TREATMENT OF

copy number alterations. As a consequence, Talhouk et


SMALL CELL LUNG CANCER: NEW HORIZONS
L.E. Trodella, M. Fiore, I. Ridolfi, L. Trodella,
S. Ramella al.3 have published and validated a new prognostic clas-
sification of EC based on the molecular categories iden-
Università Campus Biomedico, Roma, Italy tified in The Cancer Genome Atlas (TCGA): POLE
Over the past twenty years, many progresses have (polymerase-epsilon mutation), associated with an excel-
been made in the treatment of Small Cell Lung Cancer lent prognosis, MSI (microsatellite instable EC) and low
(SCLC). The addition of radiotherapy to systemic treat- copy number EC, in particular B-catenin mutated EC4,
ment and the use of Prophylactic Cranial Irradiation associated with an intermediate prognosis, high copy
(PCI) are some examples of these improvements in the number, especially P53 mutated EC, associated with un
localized and extended disease. Despite these, SCLC unfavorable prognosis. The authors developed the
continues to be one of the tumors with the worst pro- Proactive Molecular Risk Classifier for Endometrial
gnosis on the global cancer scenario. Research by Cancer (ProMisE).5 According to this new idea, the
Radiation Oncologists and Medical Oncologists to PORTEC study group elaborated a randomized clinical
improve clinical outcomes remains a challenge. This trial (the PORTEC-4a)6 investigating a molecular pro-
talk focuses on research that links improvements of cli- file-based adjuvant treatment in women with high-inter-
nical outcomes and new strategies in the treatment of mediate risk endometrial cancer (EC), comparing indi-
SCLC. This presentation highlights some of randomi- vidualized adjuvant treatment based on a molecular-inte-
zed controlled trials and “real-life” studies in patients grated risk profile to standard adjuvant treatment, as
affected by SCLC. Firstly, I will outline the research defined by the international guidelines. Our lecture will
that has be done answering to questions still open (high focus on the previous studies and will discuss the classi-
doses, extra-thorax irradiation, PCI with hippocampal fication system elaborated in our Institution, based on
sparing) and then I will focus on the studies which pro- both clinico-pathologic and molecular findings, not only
vide evidence. The talk will also present interesting per- for the HIR EC patients, but also for low-intermediate
spective trials we have to wait for the definitive results. and high risk EC patients. This will lead to a better
There will be time for the audience to give their views understanding of EC and hopefully it will improve indi-
at the end. vidualization of treatment for each patient.

References
1. Creutzberg CL, van Putten WL, Koper PC, Lybeert ML,
Jobsen JJ, Wárlám-Rodenhuis CC, De Winter KA, Lutgens
IS THERE A ROLE FOR A MOLECULAR BIOLOGY
LC, van den Bergh AC, van de Steen-Banasik E, Beerman H,
CLASSIFICATION OF RISK GROUPS TO DETER-
MINE ADJUVANT TREATMENTS IN ENDOMETRIAL van Lent M.Surgery and postoperative radiotherapy versus
surgery alone for patients with stage-1 endometrial carcino-
ma: multicentre randomised trial. PORTEC Study Group.
CANCER?
M. Campitelli1, C. Nero2, A. Santoro3, R. Autorino1, Post Operative Radiation Therapy in Endometrial
M.A. Gambacorta4 Carcinoma. Lancet. 2000 Apr 22; 355(9213):1404-11.
1Departement of Diagnostic Imaging, Radiation 2. Cancer Genome Atlas Research Network, Kandoth C,
Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H,
Oncology and Hematology, Radiation Oncology Unit, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird
Fondazione Policlinico Universitario A.Gemelli IRCSS, PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis
Roma; 2Department of Women and Children Health, ER, Levine DA. Integrated genomic characterization of
Gynecologic Oncology Unit, Fondazione Policlinico endometrial carcinoma, Nature 497 (7447) (2013) 67–73.
3. Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon
Universitario A. Gemelli IRCCS, Roma; 3Institute of JS, Melnyk N, Yang W, Senz J, Boyd N, Karnezis AN,
Histopathology, Fondazione Policlinico Universitario Huntsman DG, Gilks CB, McAlpine JN. A clinically applica-
A. Gemelli IRCCS, Catholic University of the Sacred ble molecular-based classification for endometrial cancers.
Heart, Roma; 4Departement of Diagnostic Imaging, Br J Cancer. 2015 Jul 14;113(2):299-310. doi:
10.1038/bjc.2015.190. Epub 2015 Jun 30.
Radiation Oncology and Hematology, Radiation 4. Stelloo E, Nout RA, Osse EM, Jürgenliemk-Schulz IJ,
Oncology Unit, Fondazione Policlinico Universitario Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Nijman
A.Gemelli IRCSS, Catholic University of the Sacred HW, Putter H, Bosse T, Creutzberg CL, Smit VT. Improved
Heart, Roma, Italy Risk Assessment by Integrating Molecular and
Clinicopathological Factors in Early-stage Endometrial
Endometrial cancer (EC) has generally a good prog- Cancer-Combined Analysis of the PORTEC Cohorts. Clin
Cancer Res. 2016 Aug 15;22(16):4215-24. doi:
nosis because it is typically diagnosed at low stage and 10.1158/1078-0432.CCR-15-2878. Epub 2016 Mar 22.
low grade is the most common subtype. Although this, 5. Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz
EC in about 20% of patients, has an unexplained aggres- J, Boyd N, Pike J, Anglesio M, Kwon JS, Karnezis AN,
sive behavior that cannot be justified by its clinico-patho- Huntsman DG, Gilks CB, McAlpine JN. Confirmation of
ProMisE: A simple, genomics-based clinical classifier for
logic findings. In clinical practice, radiation treatment of endometrial cancer. Cancer. 2017 Mar 1;123(5):802-813.
EC is decided according to a classification into prognos- doi: 10.1002/cncr.30496. Epub 2017 Jan 6.
tic risk groups derived from the well-known and historic 6. B.G.Wortman, T. Bosse, R.A. Nout, L.C.H.W. Lutgens, E.M.
PORTEC study1 which takes in consideration the tumor van der Steen-Banasik, H.Westerveld, H. van den Berg, A.
Slot, K.A.J. DeWinter, K.W. Verhoeven-Adema, V.T.H.B.M.
type and grade, the stage and the presence of lymphovas- Smit, C.L. Creutzberg, for the PORTEC Study Group.
cular space invasion. In 2013, TCGA2 analyzed the Molecular-integrated risk profile to determine adjuvant

| 17 |
Programme

radiotherapy in endometrial cancer: Evaluation of the pilot tly the quality and accuracy in radiotherapy. Recently,
phase of the PORTEC- 4a trial. Gynecol Oncol. 2018 we are entering in a new technological era where on-
Oct;151(1):69-75. doi: 10.1016/j.ygyno.2018.07.020. Epub
2018 Aug 3 board Magnetic Resonance Imaging guided-radiothe-
rapy with hybrid MR-Linac accelerator systems will
allow a direct tumor and surrounding organ at risk
(OAR) real-time visualization. Elekta Unity™ is a
hybrid Linac with an on-board 1.5 Tesla (T) MR. This
ADJUVANT RADIOTHERAPY AND

system received FDA approval in 2018 and it is now


CHEMOTHERAPY IN ENDOMETRIAL CANCER:

available for clinical use. The 1.5 T on-board MR pro-


WHEN, HOW AND WHY
P. Vitali, F. Barbera, F. Frassine, S. Pedretti,
D. Tomasini, M. Bonù, S.M. Magrini vide high quality morphological and functional ima-
ging, both useful in radiation oncology clinical practice.
Radiation Oncology Department, University and More specifically, morphological imaging are used for
Spedali Civili Hospital, Brescia, Italy
adaptive strategies due to its high resolution with no
Endometrial cancer is the most common gynecolog- additional ionizing radiation administration. Moreover,
ical cancer in developed countries. Most patients are functional sequences could be relevant for potential
diagnosed at an early stage with a low risk of relapse. predictive evaluation in the radiomics era.
However, there is a group of patients with a high risk of Method: In July 2019, the Advanced Radiation
relapse and poor prognosis. The optimal adjuvant treat- Oncology (ARO) Department at IRCCS Sacro Cuore
ment for endometrial cancer remains poorly defined Don Calabria Hospital completed the first 1.5 T MR-
despite the prevalence of the disease and a large number Linac installation in South Europe. A clinical protocol
of completed prospective studies. This ambiguity can with the aim to define 1.5 T MR-Linac oncological eli-
be attributed to inadequate power in many of these stud- gible patients was produced by the collaboration
ies due to heterogeneity in patient selection criteria, low between with Rete Oncologica Veneta (ROV) and
recurrence rates in early stage endometrial cancer, and Regione Veneto.
competing risk of death from other causes in women Results: Four different oncological scenario have
with endometrial cancer. The most important prognos- been defined: 1) low-intermediate risk prostate cancer
tic factors identified in endometrial cancer are: FIGO eligible to a radical treatment, with a maximum volume
stage, histological subtype, grade, depth of myometrial of 80 cc and an International Prostate Symptom Score
invasion, lymphovascular space invasion (LVSI), and (IPSS) <15; 2) inoperable or borderline pancreatic can-
age. In the near future, the molecular advances could be cer; 3) oligometastatic patients with ≤4 disease presen-
used for outcome prediction and may aid in optimal dis- tation (including primary tumor) and a maximal diame-
tinction of the risk groups. Many Institutions try to pro- ter of 40 mm; 4) re-irradiation of soft tissue, brain, head
vide evidence-based guidelines for adjuvant therapy in and neck, abdominal or pelvic disease in patients with
the treatment of endometrial cancer. Despite the recent good performance status (0-1) and a previous radiation
publication of randomized trials, the adjuvant treatment treatment for at least 6 months. A total number of 230
of endometrial cancer is still to be defined and there are patients will be recruited. The primary outcome is to
many open questions about the best approach and the collect real data of patients treated with 1.5 T MR-
right timing. Linac. Secondary outcomes are to define the feasibility
of the treatment procedures, a workflow process and
evaluate cost/benefit in order to establish a reimburse-
References ment by Regione Veneto and the National Health
Colombo, N., et al. (2016) ESMO-ESGO-ESTRO Consensus System.
Conference on Endometrial Cancer: Diagnosis, Treatment Conclusions: Hybrid 1.5 T MR-Linac system is an
and Follow-Up, International Journal of Gynecological
Cancer 27(1), 2-30. innovative technological approach, which might change
Klopp A. et al (2014) The Role of Postoperative Radiation modern radiotherapy clinical practice. In October 2019,
Therapy for Endometrial Cancer: An ASTRO Evidence- the first oncological patient will receive a radiation
Based Guideline, Practical Radiation Oncology treatment with 1.5 T MR-Linac and we are expecting to
De Boer SM, et al. Final results of the international randomized
PORTEC-3 trial of adjuvant chemotherapy and radiation complete the accrual in 12 months.
therapy (RT) versus RT alone for women with high-risk
endometrial cancer. J Clin Oncol. 2017;35S:5502. Reference
1 Corradini S, Alongi F, Andratschke N, et al. MR-guidance in
clinical reality: current treatment challenges and future per-
spectives. Radiat Oncol. 2019;14(1):92. doi:
MR-LINAC: INITIAL EXPERIENCE AT SACRO
CUORE DON CALABRIA HOSPITAL 10.1186/s13014-019-1308-y
F. Alongi1,2, N. Giaj-Levra1, L. Nicosia1, F. Ricchetti1
1Advanced Radiation Oncology Department, IRCSS

Sacro Cuore Don Calabria Hospital, Negrar-Verona,


Italy; 2University of Brescia, Brescia, Italy
Aim: A combination of high precision radiation
techniques and daily set-up verification with the use of
on-board cone-beam CT (CBCT) increased significan-

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

THE ONCOLOGICAL RADIOTHERAPIST REGARDS TRIPLE NEGATIVE BREAST CANCER: DOES CEL-
TO THE NEW EUROPEAN REGULATIONS LULAR HETEROGENEITY GUIDE OUR MEDICAL
F. Lucà DECISIONS?
Fondazione Area Radiologica, Roma, Italy I. Desideri
Università di Firenze, Italy
The Directive is the new Business Support System.
Important technological and scientific developments Chemotherapy is the primary established systemic
have determined a considerable increase of patient treatment for patients with triple-negative breast cancer
exposure. The Directive highlights the necessity of jus- (TNBC) in both the early and advanced-stages of the
tifying exposure and information offered to the patients. disease. The lack of targeted therapies and the poor pro-
The quality of programms developed and dealt with by gnosis of patients with TNBC have fostered a major
the insurance companies is necessary, including the effort to discover actionable molecular targets to treat
study of the risks of radiotherapy. A high level of com- patients with these tumours. Massively parallel sequen-
petence is fundamental and a clear definiton of respon- cing and other 'omics' technologies have revealed an
sability of tasks taken out by all the professionals,doc- unexpected level of heterogeneity of TNBCs and have
tors, fisicists and technicians for an adeguate protection led to the identification of potentially actionable mole-
of the patients who have to undergo a procedure of cular features in some TNBCs, such as germline
medical therapy. The dosage in oncological therapy rep- DTEC314 mutations or 'BRCAness', the presence of the
resents one of the most important points, of around androgen receptor, and several rare genomic alterations.
which rotates medical exposure for curative perform- A subgroup of TNBCs shows a high degree of tumour-
ance, neoplastic control, or/and palliatives. The State infiltrating lymphocytes that also correlates with a
members ensure that the specialist in Medical Physics is lower risk of disease relapse and a higher likelihood of
responsible of the dosage, including the fisical meas- benefit from chemotherapy. Proof-of-principle studies
ures for the rating of the doses administered to the with immune-checkpoint inhibitors in advanced-stage
patient and other people who are subject to medical TNBC have yielded promising results, indicating the
exposure. The final responsability of treatment and care potential benefit of immunotherapy for patients with
remains that of the Radiotherapist. The Directive 59/13 TNBC. The efficacy of programmed cell death protein
defines and promotes more the role of the medical 1 (PD-1) blockade in metastatic triple-negative breast
physic inside the assistance structure of radiotherapy. cancer (TNBC) is low, highlighting a need for strategies
On the 25 May 2019 terminated the period of tollerance that render the tumor microenvironment more sensitive
for the execution of GDPR on privacy which entered to PD-1 blockade. Preclinical research has suggested
into force in 2018. Il Guarantor has adopted a uniform immunomodulatory properties for chemotherapy and
interpretation for healthcare. Doctors can treat dates of irradiation. Starting from this context, both pre-clinical
their patients for treatment purposes without having to and clinical data involving the combination of systemic
ask their consent, but must give complete information therapy and radiotherapy for the treatment of TNBC
on what these dates will be used for. Necessity of con- will be addressed.
sent for handling of data relative to an electronic health
dossier or for consultation of referts on line. Disclosures
have to be concise, transparent, comprehensible and
easily attainable, written simply and clear and must
THERAPEUTIC APPROACHES IN BRCA MUTATION

contain information regarding, for example, those con-


CARRIERS BREAST CANCER PATIENTS: WHEN

cerning the period of conservation of the dates. The


GENETICS HELPS THE CLINIC
M.C. Leonardi1, A. Morr1, M.A. Gerardi1,
Authorities clarify that it is obligatory for all health S. Dicuonzo 1, D P. Rojas1, M. A. Zerella1,5,
operators to keep a register where all the activities of E. La Rocca1,5, A.M. Ferrari1, B. Bonanni2,
handling of data are listed of each patient. This docu- E. Munzone3, R. Orecchia4, B.A. Jereczek-Fossa1,5
ment represents an essential element for the manage- 1Division of Radiation Oncology, European Institute of
ment of treatments and for an effective detection of
those at greater risk , and for demonstrating the respect Oncology,IRCCS, Milan; 2Division of Cancer
of the principle of accountability. It underlines that Prevention & Genetics European Institute of
Oncology,IRCCS, Milan; 3Division of Medical Senology
every project based on artificial intelligence should
European Institute of Oncology, IRCCS, Milan;
respect human dignity and the basic princple of lawful- 4Scientific Directorate, European Institute of
ness, fairness, specification of purpose, proportionality
Oncology,IRCCS, Milan; 5Department of Oncology and
of the treatment, protection of dates right from the
Hemato-Oncology,University of Milan, Italy
design, responsability, transparency, safety of dates and
management of risks. Triple negative breast cancer (TN BC) patients are
characterized by earlier recurrences, decreased survival
and high rate of distant metastases,1 mainly to the brain
and lungs, while liver, bone and lymph nodes are less
frequently involved. The TNBC is an heterogeneous
group, including also tumors with basal phenotype and
BRCA mutation. BRCA-related BC frequently pres-

| 19 |
Programme

ent DNA repair defects, TP53 mutations and defective chemotherapy (capecitabine, eribulin, gemcitabine,
G2/M checkpoint activation in response to DNA dam- vinorelbine). Understanding the alteration in tumor
age, genomic instability and disorganized apoptotic biology, especially the deficiency in DNA repair path-
mechanisms.2 As a result, although TNBCs are consid- ways, show a potential in future cancer therapy.
ered resistant to standard chemotherapy, those associat-
ed to BRCA dysfunction present higher sensitivity to References
oncologic therapies, which might lead to better 1. Chiorean R, Braicu C, Berindan-Neagoe I Another review
response.3 The BRCA1/2- dysfunction resulting in on triple negative breast cancer. Are we on the right way
defective DNA repair pathways is known as towards the exit from the labyrinth? The Breast 22 (2013)
“BRCAness. The DNA damage induced by radiation or 1026e1033
2. Jameel JK, Rao VS, Cawkwell L, Drew PJ.Radioresistance
chemotherapeutic agents is magnified by a mutation in in carcinoma of the breast. Breast. 2004 Dec;13(6):452-60.
BRCA genes, which are either ‘gatekeeper’ (control- 3. Robson ME, Chappuis PO, Satagopan J, et al. A combined
ling cell cycling, proliferation and apoptosis) and analysis of outcome following breast cancer: differences in
‘caretaker’ (correcting errors and repairing DNA). This survival based on BRCA1/BRCA2 mutation status and
administration of adjuvant treatment. Breast Cancer Res.
synergism is known as synthetic lethality. Radiation- 2004;6:R8–R17
induced DNA damage essentially consists of base dam- 4. Kucharczyk MJ, Parpia S, Walker-Dilks C et al. Ablative
age, single-strand breaks, and double-strand breaks Therapies in Metastatic Breast Cancer: A Systematic
(DSB). Patients with oligometastases BC can benefit Review.Breast Cancer Res Treat. 2017 Jul;164(1):13-25
5. Yardley DA, Coleman R, Conte P, et al. nab-Paclitaxel plus
for ablative radiation treatment with the aim of achiev- carboplatin or gemcitabine versus gemcitabine plus carbo-
ing cure or prolonged survival, although the hetero- platin as first-line treatment of patients with triple-negative
geneity of the population and treatment schemes, the metastatic breast cancer: results from the tnAcity trial.Ann
Oncol. 2018 Aug 1;29(8):1763-1770.
absence of randomized trials, has not yet pinpointed the 6. Twelves C, Cortes J, Vahdat L, et al .Efficacy of eribulin in
best candidates.4 Chemotherapeutic agents can act at women with metastatic breast cancer: a pooled analysis of
different levels, based on destabilizing the DNA two phase 3 studies.Breast Cancer Res Treat. 2014
through intercalation (anthracyclines), affecting DNA Dec;148(3):553-61.
7. Tutt A, Tovey H, Cheang MCU,et al Carboplatin in
repair cascade by targeting genomic instability (tax- BRCA1/2-mutated and triple-negative breast cancer
anes), the G2–M phase of the cell cycle (Eribulin), BRCAness subgroups: the TNT Trial. Nat Med. 2018
PARP inhibitors give rise to accumulation of DSB. May;24(5):628-637.
First- line agents comprise combinations with platins 8. Isakoff SJ, Mayer EL, He L,et al.TBCRC009: A Multicenter
Phase II Clinical Trial of Platinum Monotherapy With
(carboplatin/cisplatin) and taxanes or anthracyclines Biomarker Assessment in Metastatic Triple-Negative Breast
plus cyclophosphamide. The phase II study tnAcity Cancer. J Clin Oncol. 2015 Jun 10;33(17):1902-9
showed that the combination of nab-paclitaxel and car- 9. Litton JK, Rugo HS, Ettl J,et al .Talazoparib in Patients with
boplatin significantly prolongs progression free sur- Advanced Breast Cancer and a Germline BRCA Mutation. N
Engl J Med. 2018 Aug 23;379(8):753-763.
vival (PFS) compared to nab-paclitaxel + gemcitabine 10. Robson M, Goessl C, Domchek S.Olaparib for Metastatic
and gemcitabine+carboplatin.5 At progression, the use Germline BRCA-Mutated Breast Cancer.N Engl J Med. 2017
of PARPis, fluorouracil/capecitabine, eribulin, gemc- Nov 2;377(18):1792-3
itabine, cisplatin/carboplatin, vinorelbine are alterna-
tives. The effects of anthracyclines are based on desta-
bilizing the DNA through intercalation while taxanes
affect DNA repair cascade by targeting genomic insta-
NOVEL APPROACHES IN HER2 POSITIVE BREA-

bility. Eribulin the G2–M phase of the cell cycle and


ST CANCER DISEASE
M.C. De Santis1, C. Giandini1,2, M. Dispinzieri1,
disrupts the mitotic spindle architecture, eliciting accu- R. Valdagni3, S. Di Cosimo4, L. Lozza1
mulation of double-stranded DNA breaks (PARP 1Radiotherapy Unit 1, Fondazione IRCCS Istituto
inhibitors). Eribulin as first line or further-line setting
Nazionale dei Tumori, Milan, Italy; 2Department of
significantly improved overall survival, especially in
Oncology and Hemato-oncology, Università degli Studi
TNBCs.6 Regarding the use of platinum salts, while in
di Milano; 3Department of Oncology and Hemato-onco-
TNBCs patients not selected according to BRCA status,
logy, Università degli Studi di Milano. Director,
carboplatin was not more effective than docetaxel, in
Radiation Oncology 1 and Prostate Cancer Program,
patients with BRCA mutation, the objective response
Fondazione IRCCS Istituto Nazionale dei Tumori,
rate (ORR) doubled with carboplatin compared to doc-
Milan, Italy; 4Department of Applied Research and
etaxel.7 Similar results were also obtained in the phase Technological Development (DRAST), Fondazione
II study TBCR009, where the ORR was 54.5% in IRCCS Istituto Nazionale dei Tumori, Milan, Italy
patients with BRC mutation compared to 25.6% in uns-
elected population.8 In this settings, the knowledge of Overexpression of the human epidermal growth
BRCA status led to better outcome. Regarding PARP- factor receptor type 2 (HER2) occurs in approximately
inhibitors, the results of 2 phase III trials, Olympiad 15 to 20% of invasive breast cancers and was historical-
and EMBRACA,9,10 enrolling HER2 negative metasta- ly associated with poor clinical outcomes. In recent
tic BC with germline mutation of BRCA gene, pretreat- years, numerous published studies have changed the
ed with up to 2 lines of chemotherapy, showed a higher type of treatment in Her 2 positive disease: 1)
ORR and median PFS in patients receiving ParP Neosphere1 demonstrated that pertuzumab and trastu-
inhibitors than control arm consisting of standard zumab plus docetaxel significantly increased the patho-

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

logical complete response (pCR) rate vs other arms; 2) 4. Neratinib after trastuzumab-based adjuvant therapy in
APT study2 evaluated the possibility of omitting anth- HER2-positive breast cancer (ExteNET): 5-year analysis of a
randomised, double-blind, placebo-controlled, phase 3 trial.
racyclines for patients with stage I HER2-positive brea- Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B,
st cancer (BC); 3) Katherine study3 demonstrated an Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH,
advantage of Trastuzumab emtansine in reducing the Gnant M, Tomašević Z, Denduluri N, Šeparović R, Gokmen
risk of recurrence in some HER2- positive breast can- E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH,
Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong
cers following neoadjuvant chemotherapy and with AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu
residual disease; 4) ExteNET4 showed that 1 year of F, Auerbach A, Buyse M, Chan A; ExteNET Study Group.
neratinib, an irreversible pan-HER tyrosine kinase inhi- Lancet Oncol. 2017 Dec;18(12):1688-1700. doi:
10.1016/S1470-2045(17)30717-9. Epub 2017 Nov 13.
bitor, significantly improves 2-year invasive disease- 5. Intrinsic subtypes and benefit from postmastectomy radio-
free survival after trastuzumab-based adjuvant therapy therapy in node-positivepremenopausal breast
in women with HER2- positive BC. HER2-positive BC cancer patients who received adjuvant chemotherapy -
has high radioresistance that is correlated to the transac- results from two independent randomized trials. Laurberg
T, Tramm T, Nielsen T, Alsner J, Nord S, Myhre S, Sørlie
tivation of the NF- κ B-mediated HER2 promoter indu- T, Leung S, Fan C, Perou C, Gelmon K, Overgaard J, Voduc
cing HER2 overexpression, β-catenin expression during D, Prat A, Cheang MCU. Acta Oncol. 2018 Jan;57(1):38-43.
epitelial mesenchimal transition (EMT) and the Fak- doi: 10.1080/0284186X.2017.1401735. Epub 2017 Nov 25.
mediated pathway.5 The role of elective nodal irradia- 6. Regional Nodal Irradiation After Breast Conserving Surgery
for Early HER2-Positive Breast Cancer: Results of a
tion (ENI) in ypN0 patients following neoadjuvant che- Subanalysis From the ALTTO Trial. Gingras I, Holmes E, De
motherapy and in pN1-3 Her 2 positive breast cancer Azambuja E, Nguyen DH, Izquierdo M, Anne Zujewski
patients is not clear. Few and retrospective data are J, Inbar M, Naume B, Tomasello G, Gralow JR, Wolff
available in literature.6-7 No clinically accepted bio- AC, Harris L, Gnant M, Moreno-Aspitia A, Piccart MJ, Azim
HA Jr. J Natl Cancer Inst. 2017 Aug 1;109(8). doi:
markers are as yet available to predict the response to 10.1093/jnci/djw331.
anti-HER2 therapy. Therefore, novel approaches to esti- 7. Indications for Postmastectomy Radiation After
mate clinical outcomes of HER2-targeted therapy are Neoadjuvant Chemotherapy in ypN0 and ypN1-3 Axillary
Node-Positive Women. Fowble B, Jairam AK, Wang F, Peled
still needed. Plasma miRNA or Circulating Tumor DNA 8-9 A, Alvarado M, Ewing C, Esserman L, Park C, Lazar A. Clin
gave promising evidence for further examination of Breast Cancer. 2018 Feb;18(1):e107-e113. doi:
response to anti-HER2 agents. A radiogenomic signatu- 10.1016/j.clbc.2017.07.016. Epub 2017 Aug 1.
re from the tumor and its environment, characterizing 8. Circulating Tumor DNA in HER2-Amplified Breast Cancer:
A Translational Research Substudy of the NeoALTTO Phase
the response-associated HER2-E subtype, was identi- III Trial. Rothé F, Silva MJ, Venet D, Campbell C, Bradburry
fied in a recent study, applied to estimate response to I, Rouas G, de Azambuja E, Maetens M, Fumagalli
anti-HER2 therapy and then correlated with pathologic D, Rodrik-Outmezguine V, Di Cosimo S, Rosa D, Chia
immune response on corresponding biopsy images.10 S, Wardley A, Ueno T, Janni W, Huober J, Baselga J, Piccart
M, Loi S, Sotiriou C, Dawson SJ, Ignatiadis M. Clin Cancer
With additional validation, these features could even- Res. 2019 Jun 15;25(12):3581-3588. doi: 10.1158/1078-
tually result in a non invasive method to help characte- 0432.CCR-18-2521. Epub 2019 Mar 12.
rize tumor biological characteristics in HER2+ tumors 9. Plasma miRNA Levels for Predicting Therapeutic Response
and evaluate benefits of targeted therapy. to Neoadjuvant Treatment in HER2-positive Breast Cancer:
Results from the NeoALTTO Trial. Di Cosimo S, Appierto
V, Pizzamiglio S, Tiberio P, Iorio MV, Hilbers F, de
Azambuja E, de la Peña L, Izquierdo M, Huober J, Baselga
References J, Piccart M, de Braud FG, Apolone G, Verderio P, Daidone
MG. Clin Cancer Res. 2019 Jul 1;25(13):3887-3895. doi:
1. 5-year analysis of neoadjuvant pertuzumab and trastuzumab 10.1158/1078-0432.CCR-18-2507. Epub 2019 Feb 27.
in patients with locally advanced, inflammatory, or early- 10. Association of Peritumoral Radiomics With Tumor Biology
stage HER2-positive breast cancer (NeoSphere): a multicen- and Pathologic Response to Preoperative Targeted Therapy
tre, open-label, phase 2 randomised trial. Gianni for HER2 (ERBB2)-Positive Breast Cancer. Braman
L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch N, Prasanna P, Whitney J, Singh S, Beig N, Etesami M, Bates
A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini DDB, Gallagher K, Bloch BN, Vulchi M, Turk P, Bera
JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit K, Abraham J, Sikov WM, Somlo G, Harris LN, Gilmore
V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross H, Plecha D, Varadan V, Madabhushi A. JAMA Netw
G, Valagussa P. Lancet Oncol. 2016 Jun;17(6):791-800. doi: Open. 2019 Apr 5;2(4):e192561. doi: 10.1001/jamanet-
10.1016/S1470-2045(16)00163-7. Epub 2016 May 11. workopen.2019.2561.
2. Adjuvant paclitaxel and trastuzumab for node-
negative, HER2-positive breast cancer. Tolaney SM, Barry
WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain
KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey
LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop
CONTOURING AND SET-UP IN THE TREATMENT
IE, Burstein HJ, Winer EP. N Engl J Med. 2015 Jan
OF LIVER METASTASIS
8;372(2):134-41. doi: 10.1056/NEJMoa1406281. L. Caravatta
3. Trastuzumab Emtansine for Residual Invasive HER2- SS Annunziata Hospital Radiation Oncology Unit,
Positive Breast Cancer. von Minckwitz G, Huang CS, Mano
MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi Chieti, Italy
P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin
AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna The liver is a common site of metastases and in
MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota some cases it may be the only site of disease. Over the
Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt past decade, there has been an increasing use of radio-
M, Douthwaite H, Singel SM, Geyer CE therapy (RT) for the treatment of liver metastases, and
Jr; KATHERINE Investigators. N Engl J Med. 2019 Feb
14;380(7):617-628. doi: 10.1056/NEJMoa1814017. Epub most often, in selected patients with oligometastases
2018 Dec 5. and limited liver involvement, ablative doses are deliv-

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ered to focal liver metastases, instead of whole-liver patients with un-resectable liver metastases enrolled in
RT, aiming to improve time to progression and overall Phase I and II Trials on liver SBRT. Toxicity was
survival.1 Ablative RT, using stereotactic body RT focused on - although not limited to - the clinical and
(SBRT), involves immobilization and high precision radiological appearance of the radiation-induced liver
treatment planning, typically resulting in highly confor- disease (RILD).
mal dose distributions encompassing the planning tar- Results: Phase I/II clinical trials show local control
get volume (PTV) with steep dose gradients toward the rates between 60% and 100%, respectively, in patients
surrounding normal tissue. Multimodal imaging, accu- with HCC and liver metastases. Interpretation of the
rate outlining of the gross tumor volume (GTV) and the reported survival rates is confounded by the significant
clinical targeting volume (CTV), advanced planning, heterogeneity in the included patients. Clinical features
IGRT, and motion management are then mandatory to and dosimetric parameters should be tailored on candi-
improve the treatment accuracy. Extensive data has dates to SBRT in order to reduce the occurrence of
been published describing advantages and drawbacks of adverse reactions. Most series have reported low rates
computed tomography (CT) or magnetic resonance of treatment toxicity, with rates of CTCAE grade 3 or 4
imaging (MRI) for GTV delineation for liver metas- toxicity (range from 1 to 10%). About RILD most stud-
tases. Moreover, it remains questionable if microscopic ies have reported rates of < 1% of RILD after SBRT in
tumor spread beyond the macroscopic tumor border or treatment of liver metastases.
tumor capsule can reliably be evaluated with the current Conclusions: Several studies have demonstrated
imaging methods. Few studies have analyzed micro- that SBRT for liver lesions is associated with optimal
extension characteristics in liver metastasis. In control rates and low toxicity profile (uncommon G3
histopathologic specimens, liver metastases from col- gastrointestinal toxicity), confirming that it may repre-
orectal cancer frequently show microscopic tumor sent a safe and effective alternative local therapy for
spread beyond the tumor margin (microsatellites) and a liver lesions.
safety margin should be applied to consider them. T1w
or T2w MRI are recommend to ensure that the target
volume contains “macroscopic” tumor, and also poten-
tially tumor cell-baring inflammatory reaction or
DELIVERY TECHNIQUES FOR THE RADIOTHERA-
microsatellites.2 In addition, data from 129 patients with
PY TREATMENT OF LIVER METASTASIS
liver metastases from colorectal cancer showed that the M. Maddalo, P. Borghetti, M. Bonù, F. Frassine,
extent of tumor invasion (62.8% patients, between 1.0 M. Buglione, S.M. Magrini
− 7.0 mm) correlated with high levels of CEA (p = Radiation Oncology Department ASST Spedali Civili di
0.002), primary tumor site in colon (p=0.008), and mul- Brescia, Brescia University, Italy
tiple lesions (p=0.045). These predictors factors may
For liver tumors, precise stereotactic body radio-
potentially be used as a scoring system for determining
GTV-to-CTV expansion.3 Finally, it is agreed that in therapy (SBRT) delivery with advanced motion man-
SBRT for liver metastases, a safety margin should be agement techniques can have an impact on treatment
added to the tumor visible in CT and/or MRI to com- success as a large multi-center analysis has recently
pensate for residual respiratory tumor motion and setup reported.1 Developments in SBRT technology have
inaccuracies. allowed the application of high radiation doses with
minimal safety margins.
References The two main delivery methods with advanced
motion management are 1) a free-breathing treatment
1. Høyer M et al. Int.J.Rad.Onc.Biol.Phys. (2012) 82:1047– with tumor tracking and 2) a linac-based gating in deep
1057
2. Pech M et al. Strah.Onkol (2008) 184:256–61 inspiration breath-hold (DIBH) with additional ultra-
3. Qian Y et al. Rad.Oncol. (2015)10:125 sound monitoring. Less sophisticated techniques with-
out advanced motion management are also reported in
literature (e.g. internal-target-volume concept, mid-
ventilation principle or gating approach in a planning
study based on 4D dose calculations with or without
DOSE-CONSTRAINTS AND TOXICITY
R.M. Niespolo, S.Terrevazzi, A. Romeo, R. Colciago,
M.C. Vajra, V. Tremolada, S. Arcangeli motion-compression). 1) Tumor tracking continuously
adjusts the beam aperture according to the last available
H.S.Gerardo, Monza, Italy
time-averaged position of the target. One possible
Aims: Conventional radiotherapy in the treatment approach is a CyberKnife robotic SBRT (RS) with fidu-
of liver lesions has historically played a marginal role cial-based real-time target tracking.2 Radiopaque fidu-
due to the low tolerance of the whole liver to high radi- cial markers can be implanted near the tumor and used
ation, while Stereotactic body radiotherapy (SBRT) has as surrogates for its position. Another option is to esti-
become an emerging treatment option for liver lesions mate the internal target motion from an external surro-
in patients unsuitable for surgery We aimed to analyze gate signal. However, the correlation between external
the role of SBRT in the treatment of HCC and colorectal and internal motion can be unstable. A hybrid solution
liver metastases. combines external and sparse x-ray–based internal
Methods: Local control (LC), overall survival (OS) monitoring systems and has recently been demonstrated
and progression free survival (PFS) were analyzed in for online clinical use with conventional linacs.3

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Experiences with liver SBRT have been reported also


with the Calypso system (Varian Medical Systems, Palo
RADIOTHERAPY TREATMENT IN STAGE III NSCLC

Alto, CA).4-6 Another option is tumor trailing on a mag-


ACCORDING TO EBM
F. Meacci, V. Scotti, B. Agresti, M. Perna, L. Visani,
netic resonance linear accelerator (MRI-linac), which V. Maragna, LP. Ciccone, G. Caramia, M. Mariotti,
allows for direct monitoring of intrafractional motion D. Pezzulla, V. Salvestrini, G. Stocchi, B. Guerrieri,
without being invasive, needing surrogates, or exposing L. Livi
the patient to additional radiation. A recent report inves-
tigating whether the tumor trailing on a MR-Linac can Radiation Therapy Unit, Careggi University Hospital,
improve target coverage in liver stereotactic body radi- Florence, Italy
ation therapy (SBRT) showed promising results.7 2) Non-small cell lung cancer (NSCLC) represents
Gantry-based SBRT in DIBH with additional ultra- approximately 80% of all lung cancers and 35-40% of
sound-based surveillance has also been reported as an NSCLC is in phase IIIA-IIIB at diagnosis. Stage III
effective SBRT method for liver metastases.8,9 A recent NSCLC includes very different clinical entities that
paper reported the results of a new method for assessing require very different therapeutic approaches. About
the in-vivo dose delivery accuracy of both gantry-based one-third of patients with locally advanced stage III
and robotic SBRT plans.10 The overall treatment accu- tumors are not subjected to surgery and for these
racy was below 5 mm, without statistically significant patients the results in terms of long-term outcome are
differences between the two techniques. poor.1-4
Until 1990, radiotherapy alone was the standard
References treatment for patients with inoperable NSCLC, but the
5-year survival rate was low (less than 10%).5 Over the
1. Andratschke N., Alheid H., Allgauer M., Becker G., Blanck
O., Boda-Heggemann J., et al: The SBRT database initiative
past two decades, numerous studies have shown that
of the German Society for Radiation Oncology (DEGRO): both chemotherapy and radiotherapy can prolong survi-
patterns of care and outcome analysis of stereotactic body val and are recommended as a treatment for locally
radiotherapy (SBRT) for liver oligometastases in 474 advanced disease.6
patients with 623 metastases. BMC Cancer 2018; 18: pp.
283. Combination of radiotherapy plus platinum-based
2. Andratschke N., Parys A., Stadtfeld S., Wurster S., chemotherapy for locally advanced NSCLC shows sur-
Huttenlocher S., Imhoff D., et al: Clinical results of mean vival benefits compared to radiotherapy alone and it is
GTV dose optimized robotic guided SBRT for liver metas- considered the current standard of care with median
tases. Radiat Oncol 2016; 11: pp. 74.
3. Bertholet J., Hansen R., Worm E.S., et al: Validation of a survival time for combination therapy ranging from 12
fully automatic real-time liver motion monitoring method on to 14 months compared to only radiotherapy that has a
a conventional linac. Radiother Oncol 2017; 123: pp. S247. median survival time ranging from 9 to 12 months. The
4. Worm ES, Høyer M, Hansen R, Larsen LP, Weber B, Grau C,
Poulsen PR. A Prospective Cohort Study of Gated combination of radio- and chemotherapy has been
Stereotactic Liver Radiation Therapy Using Continuous recommended by the guidelines for the treatment of
Internal Electromagnetic Motion Monitoring. Int J Radiat locally advanced diseases to reduce the risk of distant
Oncol Biol Phys. 2018 Jun 1;101(2):366-375. metastases and to maintain loco-regional control.7
5. Poulsen P.R., Worm E.S., Hansen R., et al: Respiratory gat-
ing based on internal electromagnetic motion monitoring Chemotherapy drugs can also increase the radio sensiti-
during stereotactic liver radiation therapy: First results. Acta vity of tissues and increase the effectiveness of radia-
Oncol 2015; 54: pp. 1445-1452. tion treatment.
6. James J., Cetnar A., Dunlap N.E., et al: Technical note: Combined chemotherapy and radiation therapy can
Validation and implementation of a wireless transponder
tracking system for gated stereotactic ablative radiotherapy be given simultaneously or sequentially. Although con-
of the liver. Med Phys 2016; 43: pp. 2794-2801. comitant therapy is associated with increased toxicity,
7. Fast M, van de Schoot A, van de Lindt T, Carbaat C, van der particularly at the esophageal level, several studies and
Heide U, Sonke JJ. Tumor Trailing for Liver SBRT on the
MR-Linac. Int J Radiat Oncol Biol Phys. 2019 Feb meta-analyzes indicate that concurrent therapy is supe-
1;103(2):468-478. rior to sequential therapy in the treatment of this disea-
8. Sihono D.S., Vogel L., Weiss C., Tholking J., Wenz F., Lohr se.8 However, the use of chemo-radiotherapy requires
F., et al: A 4D ultrasound real-time tracking system for exter- the total absence of negative clinical prognostic factors,
nal beam radiotherapy of upper abdominal lesions under
breath-hold. Strahlenther Onkol 2017; 193: pp. 213-220. including poor performance and weight loss.9
9. Vogel L., Sihono D.S.K., Weiss C., Lohr F., Stieler F., Wertz However, only 15% of patients who received
H., et al: Intra-breath-hold residual motion of image-guided chemo-radiotherapy were alive at 5 years; therefore it is
DIBH liver-SBRT: an estimation by ultrasound-based moni- necessary to consider the significant increase in pro-
toring correlated with diaphragm position in CBCT.
Radiother Oncol 2018; 129: pp. 441-448. gression-free survival with Durvalumab, an anti–pro-
10. Boda-Heggemann J, Jahnke A, Chan MKH, Ernst F, Ghaderi grammed death ligand 1 antibody, in patients with unre-
AL, Attenberger U, et al. In-vivo treatment accuracy analysis sectable NSCLC who who did not have disease pro-
of active motion-compensated liver SBRT through registra-
tion of plan dose to post-therapeutic MRI-morphologic alter- gression after two or more cycles of platinum-based
ations. Radiother Oncol. 2019;134:158-165. chemoradiotherapy, according to the results of the
PACIFIC trial.10

References
1. Ferlay J et al. Cancer incidence and mortality patterns in
Europe: estimates for 40 countries in 2012. Eur J Cancer

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Programme

2013; is to find which dosimetric parameter is correlated with


2. Jemal A et al. Global cancer statistics. CA Cancer J Clin which cardiotoxicity (ischemic, conduction etc). Also
2011;
3. Molina JR et al. Non-small cell lung cancer: epidemiology, contouring of the heart is controversial and should be
risk factors, treatment, and survivorship. Mayo Clin Proc standardized. The radiotherapy tec. nique is differently
2008; correlated with cardiac dose, and immunosuppression
4. Bayman N et al. How can we optimise concurrent chemora- also. Nowadays Intensity Modulated Radiation Therapy
diotherapy for inoperable stage III non-small cell lung can-
cer? Lung Cancer 2014; should always be considered the standard.
5. Perez CA et al. Impact of irradiation technique and tumor Conclusions: Cardiotoxicity is a challenging and
extent in tumor control and survival of patients with unre- important topic and prospective analysis of dosimetric
sectable non-oat cell carcinoma of the lung: report by the and clinical data should be performed.
6. O’Rourke N et al. Concurrent chemoradiotherapy in non-
References
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7. Yoon SM et al. Therapeutic management options for stage III
non-small cell lung cancer. World J Clin Oncol. 2017;
8. Curran WJ et al. Sequential vs concurrent chemoradiation for 1. Dess RT, Sun Y, Matuszak MM, Sun G et al: Cardiac Events
stage III non-small cell lung cancer: randomized phase III After Radiation Therapy: Combined Analysis of Prospective
trial RTOG 9410. J Natl Cancer Inst 2011; Multicenter Trials for Locally Advanced Non–Small-Cell
9. Crino L et al. Early stage and locally advanced (non-metasta- Lung Cancer Clin Oncol. 2017 May 1;35(13):1395-1402
tic) non-small-cell lung cancer: ESMO Clinical Practice 2. Contreras JA, Lin AJ, Weiner A, Speirs C et al: Cardiac dose
Guidelines for diagnosis, treatment and follow-up. Ann is associated with immunosuppression and poor survival in
Oncol 2010; locally advanced non-small cell lung cancer. Radiother
10. Antonia SJ et al. Durvalumab after Chemoradiotherapy in Oncol. 2018 Sep;128(3):498-504.
Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 3. Atkins KM1, Rawal B2, Chaunzwa TL3, et al: Cardiac
Radiation Dose, Cardiac Disease, and Mortality in Patients
With Lung Cancer J Am Coll Cardiol. 2019 Jun
18;73(23):2976-2987.
4. Lu Chen, Jingjuan Huang, Weihua Wu et al: The impact of
right ventricular function on prognosis in patients with stage
CARDIOTOXICITY AND OUTCOMES IN RECENT
CHEMO-RADIOTHERAPY STUDIES FOR PATIENTS III non-small cell lung cancer after concurrent chemoradio-
therapy. The International Journal of Cardiovascular Imaging
(2019) 35:1009–1017
WITH LOCALLY ADVANCES NON SMALL CELL
5. Waqar Haque, Vivek Verma, Mohamad Fakhreddine, et al:
LUNG CANCER
G. Piperno1, A.M. Ferrari1, B. Jereckzek1,2 Trends in Cardiac Mortality in Patients With Locally
1Radiotherapy Division European Institute of Oncology Advanced Non-Small Cell Lung Cancer. Int J Radiation
Oncol Biol Phys, Vol. 100, No. 2, pp. 470e477, 2018
Milan; 2University of Milan, Italy 6. Kyle Wang, Michael J. Eblan, Allison M. Deal et al: Cardiac
Toxicity After Radiotherapy for Stage III Non–Small-Cell
Aims: A literature review of radio-chemotherapy Lung Cancer: Pooled Analysis of Dose-Escalation Trials
associated cardiac toxicity studies in patients with Delivering 70 to 90 Gy. J Clin Oncol 35:1387-1394
locally advanced non small cell lung cancer treated with 7. Chia Ching Lee, Huili Zhenge, Yu Yang Soona et al:
Association between radiation heart dosimetric parameters,
curative intent. myocardial infarct and overall survival in stage 3 non-small
Results: Recently, there has been significant interest cell lung cancer treated with definitive thoracic radiotherapy
on cardiac dosimetry in the outcomes of radical treat- Lung Cancer 120 (2018) 54–59
ment for NSCLC patients, especially after results of 8. Christina K. Speirs, MD, PhD,a Todd A. DeWees, PhD,a
Sana Rehman, MD et al: Heart Dose Is an Independent
RTOG 0671 protocol and the reported “excess of car- Dosimetric Predictor of Overall Survival in Locally
diac related deaths”. Radiation-induced heart disease Advanced Non–Small Cell Lung Cancer Journal of Thoracic
can manifest as a number of cardiac disorders such as Oncology Vol. 12 No. 2: 293-301
myocardial ischemia, cardiomyopathies, conduction 9. Jianxin Xue, Chengbo Han c, Andrew Jackson et al: Doses of
radiation to the pericardium, instead of heart, are significant
abnormalities, or pericarditis. Most of cardiac events for survival in patients with non-small cell lung cancer.
occurred within 2-3 years after treatment. In the past 3- Radiotherapy and Oncology 133 (2019) 213–219
4 years many retrospective studies have been published 10. Tina Wanting Zhang, MD,* Jonatan Snir, PhD, R. Gabriel
Boldt, MLIS et al. Is the Importance of Heart Dose
on this topic. More than 100 dosimetric parameters are Overstated in the Treatment of Non-Small Cell Lung
assessed as predictors of cardiotoxicity e.g mean heart Cancer? A Systematic Review of the Literature. Int J
dose, V5, V30, V50. No clear association between any Radiation Oncol Biol Phys, Vol. 104, No. 3, pp. 582e589,
cardiac dose parameter and survival was identified in 2019
many studies; actually the relation between heart dose
and cardiac mortality is more consistent. Of course pre-
existing cardiac disease is strongly correlated with car-
THE ROLE OF PET IMAGING IN THE MANAGE-

diotoxicity and should be taken in consideration.


MENT OF OLIGO-METASTATIC RECURRENT PRO-

Intersting data are known also on effect of immunosup-


STATE CANCER
F. Ceci
pression and survival; heart dose is found to be related
Unit of Nuclear Medicine, Department of Medical
with immunosuppression (in particular with neutrophil
Sciences, University of Turin, Italy
to lymphocyte ratio). Moreover, heart dose is predic-
tive for pulmonary toxicities, and the interplay between Target treatments for locally recurrent or oligo-
heart and lung must be better defined. There is a need to metastatic recurrent prostate cancer (PCa) are gaining
find dosimetric constraints not only for the whole heart importance.1,2 Salvage therapies,3 namely early salvage
but also for all the anatomic sub-structures (pericardi- radiation therapy (SRT)4 and metastases-directed thera-
um, atria, ventricles, coronary arteries). The challenge pies,5 demonstrated to improve on patients’ outcome

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

and delaying the administration of palliative androgen- Seisen T, et al. Impact of Early Salvage Radiation Therapy in
deprivation therapy (ADT). However, these treatments Patients with Persistently Elevated or Rising Prostate-specif-
ic Antigen After Radical Prostatectomy. Eur Urol. 2017 Aug
are far to be considered curative since a non-negligible 2. pii:S0302-2838(17)30655-3. doi:
number of patients develop PSA failure after salvage 10.1016/j.eururo.2017.07.026. [Epub ahead of print].
treatments, either SRT3 or salvage pelvic lymph-node 5. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N,
dissection (S-PLND).6 Salvage therapy is only curative De Bruycker A, et al. Surveillance or Metastasis-Directed
Therapy for Oligometastatic Prostate Cancer Recurrence: A
if recurrent disease is completely encompassed by the Prospective, Randomized, Multicenter Phase II Trial. J Clin
treated volume.7,8 The effectiveness of any target the- Oncol. 2018 Feb 10;36(5):446-453.
rapy should depend on accurate imaging to rule out 6. Ploussard G, Gandaglia G, Borgmann H, de Visschere P,
areas of disease that would remain untreated. In this Heidegger I, Kretschmer A, et al. EAU-YAU Prostate Cancer
Working Group. Salvage Lymph Node Dissection for Nodal
scenario, considering the lack of sensitivity of conven- Recurrent Prostate Cancer: A Systematic Review. Eur Urol.
tional radiological imaging for recurrent PCa, together 2018 Oct 31. pii: S0302-2838(18)30836-4. doi:
with the presence of an accurate biomarker of early 10.1016/j.eururo.2018.10.041. [Epub ahead of print].
disease recurrence (PSA serum level), the presence of a 7. Farolfi A, Ceci F, Castellucci P, Graziani T, Siepe G,
Lambertini A, Schiavina R, et al. (68)Ga-PSMA-11 PET/CT
diagnostic tool able to precisely localize PCa recurrence in prostate cancer patients with biochemical recurrence after
would be crucial. Thus, there is an unmet clinical need radical prostatectomy and PSA <0.5 ng/ml. Efficacy and
to improve target delineation in patients with potential- impact on treatment strategy. Eur J Nucl Med Mol Imaging.
ly treatable PCa with early recurrence. 2019 Jan;46(1):11-19.
8. Calais J, Czernin J, Cao M, Kishan AU, Hegde JV,
The introduction of novel molecular imaging tech- Shaverdian N, et al. (68)Ga-PSMA-11 PET/CT Mapping of
nologies significantly influenced the therapy manage- Prostate Cancer Biochemical Recurrence After Radical
ment of recurrent PCa, leading to "imaging-guided" Prostatectomy in 270 Patients with a PSA Level of Less
Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning.
approaches.2 Positron emission tomography (PET) ima- J Nucl Med. 2018 Feb;59(2):230-237.
ging targeting the prostate specific membrane antigen 9. Calais J, Ceci F, Eiber M, Hope TA, Hofman MS, Rischpler
(PSMA)9 (68Ga-PSMA-11) gained importance recen- C, et al. (18)F-fluciclovine PET-CT and (68)Ga-PSMA-11
tly. At present, the use of 68Ga-PSMA-11 PET/CT has PET-CT in patients with early biochemical recurrence after
prostatectomy: a prospective, single-centre, single-arm, com-
been introduced by the European Association of parative imaging trial. Lancet Oncol. 2019 Jul 30. pii: S1470-
Urology (EAU) guidelines which currently suggest to 2045(19)30415-2. doi: 10.1016/S1470-2045(19)30415-2.
perform this imaging modality in all men with PSA fai- [Epub ahead of print].
lure after radical therapy.1 68Ga-PSMA-11 PET/CT 10. Perera M, Papa N, Roberts M, et al. Gallium-68 Prostate-spe-
cific Membrane Antigen Positron Emission Tomography in
demonstrated its higher accuracy compared to other Advanced Prostate Cancer-Updated Diagnostic Utility,
PET imaging procedures, namely choline and fluciclo- Sensitivity, Specificity, and Distribution of Prostate-specific
vine, also at low PSA levels.9,10 Membrane Antigen-avid Lesions: A Systematic Review and
Nevertheless, the real impact of 68Ga-PSMA-11- Meta-analysis. Eur Urol. Feb 14 2019.
PET/CT on patient outcome has not been tested, so far.
Despite there are strong evidences regarding the impact
of PET imaging on patient management, there is a lack
of data concerning the efficacy of PSMA-guided the-
NODAL OLIGORECURRENT PROSTATE CANCER

rapy to control the disease in the recurrent setting.


AFTER PRIMARY LOCAL TREATMENT:

Whether or not PET-positive metastasis-directed the-


WHEN IS SALVAGE LYMPH NODE DISSECTION

rapy improves progression-free or overall survival


INDICATED?
G. Giannarini
remains unclear. Furthermore, inappropriate manage-
ment due to false positive findings cannot be excluded Urology Unit, Academic Medical Centre “Santa Maria
and even if 68Ga-PSMA-11-PET/CT detects disease della Misericordia”, Udine, Italy
recurrence earlier and more accurately compared to Image-informed metastasis-directed therapy is a
other imaging modalities, the clinical implications novel and appealing treatment paradigm for patients
remain uncertain. with oligometastatic prostate cancer (PCa) [1-3]. The
aim of this lecture is to provide the latest evidence on
References the role of salvage lymph node dissection (sLND) in
1. Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, patients with nodal oligorecurrence of PCa after pri-
Gross T, et al. EAU-ESTRO-SIOG Guidelines on Prostate mary local treatment. A recent systematic review
Cancer. Part II: Treatment of Relapsing, Metastatic, and including 27 studies of men with oligorecurrent PCa
Castration-Resistant Prostate Cancer. Eur Urol. 2017
Apr;71(4):630-642. diagnosed with modern PET/CT imaging and followed
2. Ost P, Bossi A, Decaestecker K, De Meerleer G, Giannarini for a mean 29.4 months has shown that complete bio-
G, Karnes RJ, et al. Metastasis-directed therapy of regional chemical response after sLND was achieved in 13% to
and distant recurrences after curative treatment of prostate 79.5% of cases [4]. Five-year biochemical progression-
cancer: a systematic review of the literature. Eur Urol. 2015
May;67(5):852-63. free survival rates ranged from 6% to 31%, while 5-year
3. Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, overall survival rate was approximately 84%. Major
Slawin KM, Klein EA, et al. Predicting the outcome of sal- complications were observed in approximately 10% of
vage radiation therapy for recurrent prostate cancer after rad- cases, and mainly consisted of lymphoceles requiring
ical prostatectomy. J Clin Oncol. 2007 May 20;25(15):2035-
41. drainage. Main limitations were: i) retrospective design
4. Fossati N, Karnes RJ, Colicchia M, Boorjian SA, Bossi A, of single-centre series; ii) inter-study heterogeneity in

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Programme

terms of study population, definition of progression,


adjuvant treatment delivered and clinical endpoints; and
IL PUNTO DI VISTA DEL RADIOTERAPISTA

iii) lack of matched controls and long-term outcomes.


ONCOLOGO: PRO TERAPIA PELVICA
F. Matrone
In a recent multi-centre retrospective study published
after the previous meta-analysis and including 654 Department of Radiation Oncology, Centro di
patients submitted to sLND for oligorecurrent PCa, a Riferimento Oncologico di Aviano CRO-IRCCS, Italy
novel risk stratification tool to predict early (i.e. within About 80% of nodal recurrences of prostate cancer
1 year) clinical recurrence after sLND was developed (PC) are diagnosed in the pelvis.1 This pattern of
[5]. In this study, roughly 25% of men developed early relapse is correlated with a better 10-year cancer-specif-
clinical recurrence after surgery. Independent predictors ic survival compared with extrapelvic nodal recur-
of early clinical recurrence were grade group 5 (hazard rences.2 PET/CT is generally employed for the detec-
ratio [HR] 2.04; p<0.0001), time from radical prostate- tion of nodal oligometastatic disease. To date the avail-
ctomy to PSA rising (HR 0.99; p=0.025), hormonal able evidence on Metastasis Directed Therapy (MDT)
therapy administration at PSA rising after radical comes from studies in which the diagnosis of
prostatectomy (HR 1.47; p=0.0005), retroperitoneal oligometastatic disease was made mainly with Choline
uptake at PET/CT scan (HR 1.24; p=0.038), three or PET. A dedicated systematic review of Choline PET in
more positive spots at PET/CT scan (HR 1.26; nodal recurrence of PC reported a pooled detection rate
p=0.019), and PSA level at sLND (HR 1.05; p<0.0001). of 36%.3 In addition a PET/CT limitation in the “low
Based on these factors, patients who would benefit the volume” disease is represented by a limited accuracy in
most from sLND from other patients who should be defining both its exact burden (missing of the micro
spared from surgery can be quite accurately identified. metastatic disease) and its perfect distribution.4,5
In conclusion, a growing body of accumulated data sug- Although stereotactic body radiotherapy (SBRT) can
gests that sLND is a safe metastasis-directed therapy boast a higher number of dedicated studies and more
option in nodal oligorecurrence after primary local robust data to support its use in oligorecurrent disease,
treatment. However, to date, high level of evidence is some experiences suggest the whole pelvis approach
still missing to draw any clinically meaningful conclu- (WPRT) with a boost (sequential or SIB) to PET-posi-
sions about the oncological impact of sLND on long- tive nodes. In a well-known review, Ost et al. underline
term endpoints. Thus, sLND should be still regarded as the good toxicity profile of radiation treatment in olig-
an experimental treatment alternative for oligorecurrent
orecurrent disease (both SBRT and WPRT).6 The
PCa.
authors also observe how, despite the heterogeneity of
adjuvant treatments, some WPRT experiences show a
References
better outcome (1-3year PFS) compared with exclusive
1. Ost P, Bossi A, Decaestecker K, De Meerleer G, Giannarini SBRT series. More recently, Tran et al. report in a retro-
G, Karnes RJ, Roach M 3rd, Briganti A. Metastasis-directed spective study a 5-year biochemical disease-free
therapy of regional and distant recurrences after curative
treatment of prostate cancer: a systematic review of the liter- (bDFS) and a distant progression-free survival (DPFS)
ature. Eur Urol. 2015 May;67(5):852-63. doi: rates of 43% and 58%, respectively, in patients with
10.1016/j.eururo.2014.09.004. Epub 2014 Sep 17. pelvic oligorecurrent nodal PC who underwent WPRT
2. Ploussard G, Almeras C, Briganti A, Giannarini G,
Hennequin C, Ost P, Renard-Penna R, Salin A, Lebret T, with SIB.7 These data are similar to those reported by
Villers A, Soulié M, de la Taille A, Flamand V. Management Fodor et al.8 and they suggest, when compared with
of Node Only Recurrence after Primary Local Treatment for similar data from SBRT series, a possible advantage of
Prostate Cancer: A Systematic Review of the Literature. J the WPRT approach. An open issue concerns the selec-
Urol. 2015 Oct;194(4):983-8. doi: 10.1016/j.juro.
2015.04.103. Epub 2015 May 9. tion criteria for patients with pelvic oligorecurrent
3. Giannarini G, Fossati N, Gandaglia G, Cucchiara V, Ficarra nodal PC for WPRT instead of SBRT. Créhange et al.
V, Mirone V, Montorsi F, Briganti A. Will Image-guided suggest the use of WPRT in patients with multiple
Metastasis-directed Therapy Change the Treatment Paradigm
of Oligorecurrent Prostate Cancer? Eur Urol. 2018 nodal recurrences, high PSA values, PSA Doubling
Aug;74(2):131-133. doi: 10.1016/j.eururo.2018.03.021. Time <6 months or risk of lymph node involvement at
Epub 2018 Apr 4. diagnosis> 15%.9 In order to better understand the role
4. Ploussard G, Gandaglia G, Borgmann H, de Visschere P, of WPRT in this patient setting, several studies are
Heidegger I, Kretschmer A, Mathieu R, Surcel C, Tilki D,
Tsaur I, Valerio M, van den Bergh R, Ost P, Briganti A; EAU- ongoing and their results are eagerly awaited. The
YAU Prostate Cancer Working Group. Salvage Lymph Node OLIGOPELVIS GETUG P07 study is a phase II trial
Dissection for Nodal Recurrent Prostate Cancer: A that explores the role of pelvic irradiation using IMRT
Systematic Review. Eur Urol. 2018 Oct 31. pii: S0302- and SIB on PET-positive nodal sites in oligorecurrent
2838(18)30836-4. doi: 10.1016/j.eururo.2018.10.041. [Epub
ahead of print] patients with up to 5 pelvic nodes. An arm of the
5. Fossati N, Suardi N, Gandaglia G, Bravi CA, Soligo M, German PLATIN trial is focused on the role of pelvic
Karnes RJ, Shariat S, Battaglia A, Everaerts W, Joniau S, Van IMRT-SIB in a comparable setting of patients. Even
Poppel H, Rajarubendra N, Gill IS, Larcher A, Mottrie A,
Schmautz M, Heidenreich A, Kalz A, Osmonov D, more fascinating is a recently opened randomized phase
Juenemann KP, Herlemann A, Gratzke C, Stief C, Montorsi II trial: PEACE V STORM. It provides the randomiza-
F, Briganti A. Identifying the Optimal Candidate for Salvage tion of pelvic oligorecurrent patients between MDT
Lymph Node Dissection for Nodal Recurrence of Prostate with or without WPRT. By Implementing modern
Cancer: Results from a Large, Multi-institutional Analysis.
Eur Urol. 2019 Jan;75(1):176-183. doi: imaging techniques and liquid biopsies, the study aims
10.1016/j.eururo.2018.09.009. Epub 2018 Oct 6. to find the best treatment strategy in terms of

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

extrapelvic metastasis-free survival as primary end- range of 26-33%.3 The frequency of loco-regional fail-
point for this subset of patients. ure after SBRT is rather high (68%) with patterns of
recurrence occurring in outfield loco-regional nodes.4
References However, a relatively small number of men (25-38%)
1. Lépinoy A, Cochet A, Cueff A, et al. Pattern of occult nodal still remain amenable to a new course of ablative
relapse diagnosed with (18)F-fluoro-choline PET/CT in SBRT.5 An alternative approach is ENRT.6,7 In two
prostate cancer patients with biochemical failure after studies using ENRT in nodal oligorecurrent PCa,6,7 the
prostate-only radiotherapy. Radiother Oncol. 2014 3-year PFS was around 60% comparing favorably to the
Apr;111(1):120-5.
2. Giovacchini G, Picchio M, Garcia-Parra R, et al. 11C-choline data of SBRT (3-year PFS of around 26-30%).3 These
PET/CT predicts prostate cancer-specific survival in patients data was further confirmed by a recent large multi-insti-
with biochemical failure during androgen-deprivation thera- tutional, analysis conducted on 506 hormone-sensitive
py. J Nucl Med. 2014 Feb;55(2):233-41. men (SBRT: 309, ENRT: 197) with nodal oligorecur-
3. Fanti S, Minozzi S, Castellucci P, et al. PET/CT with (11)C-
choline for evaluation of prostate cancer patients with bio- rent Pca (<5 nodes).8 ENRT was associated with fewer
chemical recurrence: meta-analysis and critical review of nodal recurrences compared with SBRT. Men with one
available data. Eur J Nucl Med Mol Imaging. 2016 recurrent node had longer metastasis-free survival after
Jan;43(1):55-69. ENRT. Late toxicity was higher after ENRT compared
4. Tilki D, Reich O, Graser A, et al. 18F-Fluoroethylcholine
PET/CT identifies lymph node metastasis in patients with with SBRT (16% vs. 5%, p<0.01).8 The treatment vol-
prostate-specific antigen failure after radical prostatectomy umes for ENRT are uncertain. Spratt suggested that
but underestimates its extent. Eur Urol. 2013 May;63(5):792- extending the pelvic field superiorly to L4/L5 covered
6. 93% of men with nodal oligorecurrence.9 In line with
5. Passoni NM, Suardi N, Abdollah F, et al. Utility of
[11C]choline PET/CT in guiding lesion-targeted salvage this evidence, the use of salvage extended field radio-
therapies in patients with prostate cancer recurrence local- therapy (s-EFRT) was associated with an improved 3-
ized to a single lymph node at imaging: results from a patho- year failure rates (88.3%) compared with salvage
logically validated series. Urol Oncol. 2014 Jan;32(1):38.e9- involved field radiotherapy (s-IFRT) (55.3%). No dif-
16.
6. Ost P, Bossi A, Decaestecker K, et al. Metastasis-directed ferences were in acute or late GI and GU toxicities was
therapy of regional and distant recurrences after curative observed.10 Similarly, the optimal dose is not defined
treatment of prostate cancer: a systematic review of the liter- but some recommendations may be derived from stud-
ature. Eur Urol. 2015 May;67(5):852-63.
7. Tran S, Jorcano S, Falco T, et al. Oligorecurrent Nodal ies investigating radiation treatment of cN1 Pca at the
Prostate Cancer: Long-term Results of an Elective Nodal initial diagnosis. In this clinical setting literature recom-
Irradiation Approach. Am J Clin Oncol. 2018 mends a does ≥60 Gy EQD2 to the involved nodal GTV
Oct;41(10):960-962. and at least of 45–54 Gy EQD2 to the elective nodal
8. Fodor A, Berardi G, Fiorino C, et al. Toxicity and efficacy of
salvage carbon 11-choline positron emission region. In the SBRT, a local tumor control of 99% is
tomography/computed tomography-guided radiation therapy achievable for biological equivalent dose >100 Gy
in patients with lymph node recurrence of prostate cancer. (a/b10Gy) with a very favorable side-effect profile.3 In
BJU Int. 2017 Mar;119(3):406-413. conclusion, RT has shown to play a role in improving
9. Créhange G, Roach M, Martin E, et al. Salvage reirradiation
for locoregional failure after radiation therapy for prostate clinical outcomes of men with nodal oligorecurrent Pca.
cancer: who, when, where and how? Cancer Radiother. 2014 A significant degree of uncertainties remains and high
Oct;18(5-6):524-34. level evidence must be generated in order to provide
more definitive recommendations for this group of
patients especially in the era where new imaging
modalities can detect nodal involvement at an earlier
stage.
THE POINT OF VIEW OF THE RADIATION
ONCOLOGIST: PRO METASTASIS-DIRECTED

References
THERAPY
G.L. Gravina
Division of Radiation Oncology, Department of 1. Heidenreich A, Bastian PJ, Bellmunt J et al: EAU guidelines
on prostate cancer. Part II: treatment of advanced, relapsing,
Biotechnological and Applied Clinical Sciences, and castration-resistant prostate cancer. Eur Urol 2019; 65:
University of L'Aquila, Italy 467.
2. Lieng H, Hayden AJ, Christie DRH, Davis BJ, Eade TN,
Following primary PCa treatments a significant Emmett L, Holt T, Hruby G, Pryor D, Shakespeare TP,
number of men will recur in the loco-regional nodes.1 Sidhom M, Skala M, Wiltshire K, Yaxley J, Kneebone A.
Radiotherapy has proved its role as a metastasis-direct- Radiotherapy for recurrent prostate cancer: 2018
Recommendations of the Australian and New Zealand
ed therapy (MTD).Two strategies have been developed Radiation Oncology Genito-Urinary group. Radiother Oncol
in this clinical setting.2 They include stereotactic body 2018; 129: 377-386
radiation therapy (SBRT) and the elective nodal region 3. Ponti E, Lancia A, Ost P, et al. Exploring all avenues for
RT (ENRT), which target the entire chain in which the radiotherapy in oligorecurrent prostate cancer disease limited
to lymph nodes: a systematic review of the role of stereotac-
affected lymph node is located or the entire pelvic tic body radiotherapy. Eur Urol Focus. 2017;3(6):538-544.].
chains with integrated boost of the affected lymph 4. Ost P, Jereczek-Fossa BA, Van As N, et al. Pattern of pro-
nodes.2 A recent meta-analysis indicates the rate of gression after stereotactic body radiotherapy for
local tumor control of 98% in men receiving SBRT oligometastatic prostate cancer nodal recurrences. Clin
Oncol (R Coll Radiol) 2016; 28:e115–e120
alone for nodal oligorecurrent Pca.3 The 3-year progres- 5. Decaestecker K, De Meerleer G, Lambert B, Delrue L,
sion-free survival (PFS) in the SBRT series was in the Fonteyne V, Claeys T, De Vos F, Huysse W, Hautekiet A,

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Programme

Maes G, Ost P. Repeated stereotactic body radiotherapy for also led to the development of complex image-based
oligometastatic prostate cancer recurrence. Radiat Oncol implant stability control systems1 and quality assurance
2014; 9: 135 [26,34]
6. Fodor A, Berardi G, Fiorino C, et al. Toxicity and efficacy of protocols.4 The use of IMBT alongside the IGBT has
salvage carbon 11-choline positron emission led to major clinical and economical benefits in terms
tomography/computed tomography-guided radiation therapy of increased local control and decreased toxicity.5,6 The
in patients with lymph node recurrence of prostate cancer. need to perform complex IGBT modalities has stimulat-
BJU Int 2017; 119:406–413.
7. Schick U, Jorcano S, Nouet P, et al. Androgen deprivation ed research in the radiobiological field for the identifi-
and high-dose radiotherapy for oligometastatic prostate can- cation of increasingly hypofractional therapeutic proto-
cer patients with less than five regional and/or distant metas- cols.1,8 The main advances in the field of “planning”
tases. Acta Oncol 2013; 52:1622–1628.]. have been determined by the introduction of systems of
8. De Bleser E, Jereczek-Fossa BA, Pasquier D, Zilli T, Van As
N, Siva S, Fodor A, Dirix P, Gomez-Iturriaga A, Trippa F, “image fusion”, personalization of dose distribution,
Detti B, Ingrosso G, Triggiani L, Bruni A, Alongi F, biological planning, automatic reconstruction of
Reynders D, De Meerleer G, Surgo A, Loukili K, Miralbell catheters and improvement in calculation of dose distri-
R, Silva P, Chander S, Di Muzio NG, Maranzano E, bution considering also inhomogeneity.7,8 Particular
Francolini G, Lancia A, Tree A, Deantoni CL, Ponti E,
Marvaso G, Goetghebeur E, Ost P. Metastasis-directed attention must be paid to the reconstruction of the appli-
Therapy in Treating Nodal Oligorecurrent Prostate Cancer: A cators, especially when using Magnetic Resonance
Multi-institutional Analysis Comparing the Outcome and Imaging. These improvements in brachytherapy led to a
Toxicity of Stereotactic Body Radiotherapy and Elective progressive spread of this technique in the recent years.
Nodal Radiotherapy. Eur Urol. 2019 Jul 19. pii: S0302-
2838(19)30533-0. In the time being, many authors report about a new era
9. Spratt DE, Dess RT, Zumsteg ZS, Lin DW, Tran PT, Morgan of brachytherapy. The preliminary results of the use of
TM, et al. A systematic review and framework for the use of biological planning in brachytherapy are encouraging,
hormone therapy with salvage radiation therapy for recurrent although extensive validation is still required.9
prostate cancer. Eur Urol 2018;73:156–65.
10. Lépinoy A, Silva YE, Martin E, Bertaut A, Quivrin M, Multicenter pooling of pre-treatment and treatment
Aubignac L, Cochet A, Créhange G. Salvage extended field imaging and their correlation with clinical outcome data
or involved field nodal irradiation in 18F-fluorocholine could contribute to build predictive treatment response
PET/CT oligorecurrent nodal failures from prostate cancer. models by creating supportive tools to improve catheter
Eur J Nucl Med Mol Imaging. 2019 Jan;46(1):40-48.
placement and treatment planning.10

References
1. Innovative technologies in radiation therapy: brachytherapy.
TECHNOLOGICAL BREAKTHROUGHS IN INTER-
Hoskin PJ, Bownes P. Semin Radiat Oncol. 2006
VENTIONAL RADIOTHERAPY: BRACHYTHERAPY
L. Tagliaferri Oct;16(4):209-17.
Fondazione Policlinico Universitario ‘‘A. Gemelli’’ 2. Image guided, adaptive, accelerated, high dose brachythera-
py as model for advanced small volume radiotherapy. Haie-
IRCCS, UOC Radioterapia Oncologica, Dipartimento Meder C, Siebert FA, Pötter R. Radiother Oncol. 2011
di Diagnostica per Immagini, Radioterapia Oncologica Sep;100(3):333-43.
ed Ematologia, Roma, Italy 3. High-dose-rate (HDR) or pulsed-dose-rate (PDR) periopera-
tive interstitial intensity-modulated brachytherapy (IMBT)
In the past 20 years we have seen a significant for local recurrences of previously irradiated breast or tho-
improvement in the field of interventional radiotherapy racic wall following breast cancer. Niehoff P, Dietrich J,
Ostertag H, Schmid A, Kohr P, Kimmig B, Kovács G.
(brachytherapy) that touched in particular the “plan- Strahlenther Onkol. 2006 Feb;182(2):102-7.
ning”, the “delivery” and surgical techniques with a 4. Current brachytherapy quality assurance guidance: does it
multidisciplinary approach.1 These innovations, meet the challenges of emerging image-guided technologies?
Williamson JF. Int J Radiat Oncol Biol Phys. 2008
together with the widespread use of 3D imaging tech- 5. Multimodal therapy of anal cancer added by new endosono-
niques, such as the use of CT but also Magnetic graphic-guided brachytherapy. Doniec JM, Schniewind B,
Resonance Imaging (MRI), PET/CT and ultrasound, Kovács G, Kahlke V, Loehnert M, Kremer B. Surg Endosc.
have led to the emergence of Image Guided 2006 Apr;20(4):673-8. Epub 2006 Jan 21.
6. National Cancer Database Analysis of the effect of
Interventional Radiotherapy (or Image Guided brachytherapy on overall survival in patients with base of
BrachyTherapy, IGBT)2 resulting in important clinical tongue cancer. Silva SR, Martin B, Choi M ,et al. Head &
benefits. A significant contribution to this evolution has Neck. 2019;41:1184–1192.
come from the industry through the development of 7. Functional radiotherapy targeting used focused dose escala-
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Loading HDR and PDR devices) and high-tech applica- dose rate, high dose rate and pulsed brachytherapy. Armpilia
tors that are increasingly smaller, easier to handle and C, Dale RG, Sandilos P, Vlachos L. Phys Med Biol. 2006 Sep
MRI/CT compatible.1 The spread of single source 7;51(17)
9. Computer in brachytherapy. Van Der Laarse R, Luthman RW
devices has allowed the implementation of treatment in Joslin CAF, Flynn A, Hall EJ (eds): Principles and Practice
plans with the possibility of optimizing the coverage of of Brachytherapy Using Afterloading Systems. London,
the target by limiting the dose to organs at risk Arnold, 2001
(Intensity Modulated Interventional Radiotherapy or 10. Creating a data exchange strategy for radiotherapy research:
Towards federated databases and anonymised public
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more recently:
- Risk assessment methods of the whole procedure
TECHNOLOGICAL INNOVATIONS IN INTRAOPERA-

- Treatment planning system (TPS) and in-room


TIVE RADIOTHERAPY: IORT
C. Vidali
imaging (RADIANCE , IORT ECHO TPS)3-5
S.C. Radioterapia, Azienda Sanitaria Universitaria All these technological innovations are useful for
Integrata di Trieste, Italy the optimization of the procedure, but above all TPS
Intraoperative radiotherapy (IORT) is a special turns out to be particularly important. Planning technol-
technique allowing the delivery of a single high radia- ogy has not evolved in IORT over the years, resulting
tion dose during the surgical procedure. outdated in comparison to current state of the art in
The direct visual control of the target volume allows external radiation therapy. Only recently a planning
high precision in the delivery of the dose, avoiding the software for IORT has been launched on the market to
irradiation of the surrounding healthy tissues. It can be help in the treatment decision making process and to
combined with external beam radiation therapy (EBRT) document radio-surgical technique, target definition,
or used as a single radiation treatment.1 The first case and dosimetric beam distribution.6
was reported in 19051,2 in a patient with endometrial Technological improvement has made IORT more
cancer, and other applications were described in the feasible in a large number of Centers and may facilitate
60ies, by using single high doses of gamma-rays of the clinical advancement and thus contribute to promote
Cobalt units and electrons of Betatrons. The use of multicenter prospective trials.
IORT increased significantly in the 90ies, when dedi-
cated mobile electron linear accelerators and a minia- References
turized low-energy X-rays machine were put on the 1. Gunderson LL, Willett CG, Calvo FA, Harrison LB
market. Since then the number of patients has remark- Intraoperative Irradiation: Techniques and Results. Second
ably increased and a wider spectrum of tumor sites has edition. New York: Humana Press; 2011.
2. Krengli M, Sedlmayer F, Calvo FA, et al. “ISIORT pooled
been considered suitable for IORT. While gastro-intesti- analysis 2013 update: clinical and technical characteristics of
nal tumors, and in particular colorectal cancers, were intraoperative radiotherapy”. Transl Cancer Res 2014; 3(1):
initially the most numerous cases, nowadays early 48-58
breast cancer represents the main indication)2. 3. Hensley FW “Present state and issues in IORT Physics”
Radiat Oncol 2017; 12(1): 37 doi: 10.1186/s13014-016-
IORT may be delivered with high-energy electron 0754-z.
beams generated by conventional or “dedicated” linear 4. Calvo FA, Sole CV, Gonzales ME, et al. “Research opportu-
accelerators (Mobetron, Novac, Liac), as well as with nities in intraoperative radiation therapy: the next decade
low energy photons (Intrabeam) or with an electronic 2013-2023”. Clin Trans Oncol 2013
5. Vidali C, Severgnini M, Urbani M, et al. “FMECA
brachytherapy system (Xoft Axxent).3 Application to Intraoperative Electron Beam Radiotherapy
The technological progress involved: Procedure As a Quality Method to Prevent and Reduce
Radiation delivery, including the upgrade of the Patient’s Risk in Conservative Surgery for Breast Cancer”
IORT equipment, the development of suitable applica- Front Med (Lausanne) 2017; 4: 138-146.
6. Valdivieso-Casique MF, Rodriguez R, Rodriguez-Bescos S,
tors and shielding devices et al. “RADIANCE – A planning software for intra-operative
- Radiation dosimetry and quality assurance and radiation therapy”. Transl Cancer Res 2015; 4(2): 196-209.

| 29 |
Selected Oral Communications

Selected Oral Communications

quantified as any T2 and FLAIR changes excluding the


Gross Tumor Volume. We analyzed the temporal
B001

change of ED.
Results: Eighteen pts were treated for recurrent
PROTON THERAPY RE-IRRADIATION OF

glioblastoma and 4 for anaplastic gliomas. Median


RECURRENT HIGH-GRADE GLIOMAS:

(Med) CTV was 78,48 cc (range, 12-259 cc). Med ED


ANALYSIS OF RADIATION-INDUCED EDEMA
A. Turkaj1, D. Scartoni1, I. Giacomelli1, P. Feraco2,
B. Siniscalchi3, F. Fellin1, M. Lipparini1, volume at the baseline, mid-therapy, at the end, and 1
M. Amichetti1, D. Amelio1 month after treatment was 63 cc (range, 7-265), 83
1Centro di Protonterapia, Azienda Provinciale per I (range, 9-242), 85 (range 10-194), 69 (range 9-200),
respectively. During treatment ED increased in 16 pts
Servizi Sanitari Trento; 2Radiologia Diagnostica,
(72%) and decreased in 6 (27%). Such increase of ED
Presidio Ospedaliero Santa Chiara, Azienda
volume was associated with mild symptoms only in 8
Provinciale per I Servizi Sanitari Trento; 3U.O
Radioterapia Oncologica, Università Sapienza – pts (50%) and was controlled with modification of
Policlinico Umberto I, Roma, Italy steroids dose. One month after treatment ED decreased
in 10 pts (45%), increased in 7 (32%) and was stable in
Aims: During and after re-irradiation of relapsed 5 (23%). Six out of 7 pts (86%) with increased ED
high-grade gliomas (rHGG) variation of edema (ED) is needed modification of steroids dose. During follow up
a common event and may translate into neurological 2 pts (9%) developed radionecrosis (RN - diagnosed at
symptoms, clinical deterioration and steroid use modi- imaging) with mild symptoms controlled with steroids.
fication. In magnetic resonance imaging (MRI), ED is In pts who presented RN, ED volume increased of
usually evaluated with T2 or fluid-attenuated inversion 130% during treatment. In pts who registered increased
recovery (FLAIR) sequences. Aim of the study was to ED without RN, the mean ED volume increase during
report a quantitative analysis of radiation-induced ED the treatment was of 82%. Pts who presented RN had a
during and after proton therapy (PT) re-irradiation of mean CTV volume of 67.39 cc.
rHGG. Conclusion: PT re-irradiation of rHGG is frequently
Methods: Between January 2015 and April 2019 associated with increase of ED volume during treat-
thirty-one patients (pts) with rHGG were re-irradiated ment. Such variation often does not need modification
with PT at our institution. 22 pts underwent MRI early of steroid use. ED volume seems to decrease after the
before, during, at the end as well as 1 month after the end of the treatment. ED volume during treatment sig-
treatment and were included in the analysis. All pts nificantly increase in pts who experience RN after re-
received 36 GyRBE in 18 fractions. ED was evaluated irradiation and could predict the development of RN.
and contoured on 88 MRI scans using T2 and FLAIR CTV volume does not seems to predict the development
sequences (5 mm thickness). ED volume (in cc) was of RN.

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

B002 B003
DIFFERENTIATED THYROID CARCINOMA OF THE SINGLE FRACTION URETHRA-SPARING
PEDIATRIC AGE: GENETIC AND CLINICAL PROSTATE CANCER SBRT: PHASE I RESULTS OF
THE ONE SHOT TRIAL
C. Franzese1, T. Zilli2,3, N. Giaj-Levra4, R. Förster5,
SCENARIO
S. Talomo1, R. Abousiam1, O. Lora1, F. Galuppini2,3,
G. Pennelli2, C. Mian4, F. Vianello1 D. Zwahlen6, N. Koustouvelis2, A. Bertaut7,
1Department of Radiotherapy, Istituto Oncologico del J. Blanc7, G. D’agostino1, F. Alongi4,8,
Veneto, IOV-IRCCS, Padova; 2Pathology Unit, M. Guckenberger5, R. Miralbell2,3, M. Scorsetti1,9
1Radiation Oncology, Humanitas Research Hospital
Department of Medicine (DIMED), University-Hospital
of Padova, Italy: 3Department of Women’s and and Cancer Center, Rozzano, Milan, Italy; 2Radiation
Children’s Health, Universit Hospital of Padova, Oncology, Geneva University Hospital, Geneva,
Padova; 4Endocrinology Unit, Department of Medicine Switzerland; 3Faculty of Medicine, Geneva University,
(DIMED), University-Hospital of Padova, Italy Geneva, Switzerland; 4Radiation Oncology, Sacro
Cuore Don-Calabria, Negrar, Italy; 5Radiation
Introduction: Follicular-derived differentiated thy- Oncology, University Hospital Zürich, Zürich,
roid carcinoma is the most common endocrine and Switzerland; 6Radiation Oncology, Kantonsspital
epithelial malignancy in children. The different clinical Graubünden, Chur, Switzerland; 7Methodology and bio-
and pathological features between pediatric and adult statistic unit, Centre Georges François Leclerc, Dijon,
thyroid carcinomas could be related to a different genet- France; 8University of Brescia, Faculty of Medecine,
ic profile. However, few studies are currently available Brescia, Italy; 9Radiation Oncology, Humanitas
and most of them involved a limited number of patients University, Rozzano, Milan, Italy
and mostly focused on radiation-exposed population. A
greater knowledge of the genetics might improve the Aims: To present the phase I results of single frac-
diagnostic frame and lead to an individualized therapy. tion urethra-sparing stereotactic body radiotherapy
Materials and methods: We considered 59 pediatric (SBRT) for localized prostate cancer (PCa) from single
arm, multicenter phase I/II ONE SHOT trial.
patients who underwent surgery for diagnosis of differ-
Methods: Inclusion criteria were: cT1c-2cN0M0;
entiated thyroid carcinoma between 2000 and 2017.
Gleason ≤3+4; PSA ≤15 ng/ml; prostate volume ≤70 cc;
After surgery, Radioactive Iodine ablation/therapy was
no significant tumor in the transitional zone. Prescribed
administered to 48/51 (94%) patients. The presence of
dose was 19 Gy in single fraction to the prostate ± sem-
mutations in BRAF, NRAS, PTEN, PIK3CA genes, and
inal vesicles (PTV= CTV + 5 mm isotropic expansion,
in TERT promoter, were analyzed through sequencing. except 3 mm posteriorly). The prostatic urethra, with a
RET/PTC rearrangement has been investigated with surrounding margin of 2 mm, received a dose of 17 Gy.
Fluorescent in situ hybridization and real time poly- All patients were treated using a VMAT technique and
merase chain reaction. Clinical-molecular features of intrafractional motion control using intraprostatic elec-
pediatric patients were compared with those of 178 tromagnetic transponders. Genitourinary (GU) and gas-
adult patients. trointestinal (GI) toxicity, IPSS, IIEF-25 and QoL
Results: In pediatric age, male gender and subjects scores were assessed at baseline, at 5 days (5D), 6th
< 15 years have a more extensive disease and more fre- (6W) and 12th weeks (12W) since SBRT. Primary end-
quent lymph-nodes and distant metastases. The pres- point of the phase I was safety as assessed by occur-
ence of distant metastases resulted significantly associ- rence of Grade ≥3 acute side effects during the first 3
ated with younger age (p=0.01), higher tumor size months in a “”3 + 3”“ cohort-based.
(p<0.01), as well as with cervical lymph node metas- Results: From 08/2017 to 12/2018, 6 patients with
tases (p = 0.02). At the multivariate analysis, only the low- and intermediate-risk PCa were recruited. Median
T4 status was identified as independent predictor of dis- age and PSA at SBRT were 75 years old and 8.1 ng/ml.
tant metastases (OR 43.75, CI: 4.04 to 474.27). All pts underwent SBRT without interruption and doses
Compared to adults, in pediatric patients there is a high- constraints were respected for all plans. The toxicity
er frequency of lymph-nodes and distant metastasis stopping rule was never triggered, with no Grade ≥3
(p<0,01); moreover, pediatric patients are more prone acute side effects observed during the first 3 months.
to have a second treatment (p<0,01). The frequency of Pts experienced mostly grade 1 or 2 GU toxicities (fre-
BRAFV600E mutation is lower in pediatric DTCs quency/urgency) resolving from W6 (50% of grade 2
(p<0,01). NRASQ61R, NRASQ61K and TERTC250T GU) with no grade 2 GI side effects and no rectal toxi-
are rare in children and adolescents; no mutations were city at W12 (33% of grade 1 GI). IPSS increased from
found in PTEN and in PIK3CA. baseline to D5 and W6 (mean, from 3.5 to 13.2 and
Conclusions: Pediatric differentiated-thyroid cancer 16.2, respectively) decreasing progressively at W12
has a greater aggressiveness at diagnosis and a greater (mean, 7.2). The EPIC urinary domain mean score was
risk of recurrence than adult’s one. Differently from 92 pretreatment, 73 at D5, 79 at W6 and 87 at W12,
adult, point mutations have not a genetic key role. while the EPIC bowel domain mean score remained
overall stable over weeks (95, 91, 85, 90 at the four end-
points). No impact of SBRT was observed on IIEF-25

| 31 |
Selected Oral Communications

scores and the EPIC sexual domain between baseline Results: 510 images in 24 patients have been ana-
and W12 (mean, from 10 to 9 and from 46 to 44, respec- lyzed. Training sets had 16 patients and testing sets had
tively). The PSA values showed a bounce at D5 (mean, 8 in each repetition of the modeling processes. The
from 7.9 to 18.3 ng/ml) decreasing successively up to a summary of all training processes is summarized in
value of 3.3 ng/ml at W12. Table 1. The mean accuracy of CNN is .788, and aver-
Conclusions: Single fractions of 19 Gy SBRT on age k-statistics is .564 being very close to the perfor-
whole prostate with urethra sparing to 17 Gy was feasi- mance of P16 when compared with HPV RNA gold
ble and well tolerated. This trial represents the first mul- standard.
ticenter phase I/II trial assessing the efficacy and safety Conclusions: Despite the use of a small number of
of a single-dose SBRT monotherapy as a radical treat- patients the CNN has revealed an interesting level of
ment for localized disease. accuracy in detecting the HPV RNA patients when
compared with performance of P16. Analysis on larger
population could lead to apply this neural network in
B004
place of invasive biopsy with accuracy similar to P16
NEURAL NETWORKS BASED RADIOMICS itself.
AND HPV IDENTIFICATION IN OROPHARYNGEAL
CANCER PATIENTS
N. Dinapoli1, F. Bussu1,2, D. Di Mario3, D. Rizzo2,
Table 1. Overall 80 best models performances.

F. Miccichè1, M. Massaccesi1, M. Mendola3, Accuracy Kappa statistic Sensitivity Specificity PPV NPV
L. Boldrini1, J. Lenkowicz1, G.C. Mattiucci1,
G. Paludetti1, V. Valentini1 Mean 0.788 0.564 0.839 0.733 0.780 0.801
1Fondazione Policlinico Universitario Policlinico A. Min 0.542 0.000 0.538 0.375 0.538 0.333
Max 0.958 0.913 1.000 1.000 1.000 1.000
Gemelli IRCCS, Roma; 2Otorinolaringoiatria, Azienda
Ospedaliera Universitaria. Sassari; 3Radioterapia,
Azienda Ospedaliera Universitaria, Sassari, Italy
Aims: HPV status is a well known prognostic factor
for classifying oropharyngeal cancer (OC) patients. The
B005

definition of HPV status still uses P16 positiveness in


order to detect the cancer tissue involvement by virus.
INCORPORATING VOLUME DOSE METRICS IN

The accuracy of P16 has been proven to be lower


MACHINE LEARNING-BASED NORMAL TISSUE

respect to genetic markers like HPV DNA and RNA


COMPLICATION PROBABILITY (NTCP) MODEL

analyzed from biopsy. Radiomics is being used as a tool


OF RADIATION-INDUCED LATE DYSPHAGIA

to classify patients images and to identify classes


(RILD) RESULTING FROM HEAD AND NECK

according different type of outcomes. In this field neu-


CANCER CHEMO-IMRT
S. Ursino1, A. Giuliano2, F. Di Martino2, P. Cocuzza1,
ral networks represent an application of artificial intel- S. Montrone1, A. Molinari1, S. Santopadre3,
ligence being largely adopted in many computer sci- P. Giusti4, A. Gonnelli1, D. Baldaccini1, F. Fattori3,
ence and radiological tasks. Aim of this work is to build F. Paiar1
a classifier to detect HPV+ patients without using biop- 1U.O. Radioterapia Oncologica Universitaria; Azienda
sy and invasive or expensive techniques. This classifier
has been built by training a convolutional nerural net- Ospedaliera Universitaria Pisana; 2U.O. Fisica
work (CNN). Medica; Azienda Ospedaliera Universitaria Pisana;
3U.O. Audiologia e Foniatria Universitaria, Azienda
Methods: OC patients, with available T2fs MR
Ospedaliera Universitaria Pisana; 4U.O.
axial images and HPV RNA and P16 status defined on
Radiodiagnostica Universitaria 1, Azienda Ospedaliera
bioptic samples have been recruited. Nodal and primary
Universitaria Pisana, Italy
GTVs have been delineated on MR images and ROIs
containing the voxel data representation have been ana- Aims: To develop a predictive NTCP model for
lyzed by an in-house developed software. A CNN has severe RILD upon a prospective monocentric study by
been trained splitting the outcome of patients between introducing SWOARs in the DVH analysis and using
RNA+ and RNA-. The training process has been machine learning approach.
achieved by dividing the patients dataset in a training Methods: Naso and oropharynx cancers (Stage II-
and a testing set with 75% and 25% of total number in IVA) candidates for radiochemotherapy requiring bilat-
each subset. During training phase the model perfor- eral neck irradiation were enrolled. A dysphagia assess-
mance has been tuned by calculating the accuracy on ment including Videofluoroscopy was performed to
the testing set. Having at disposal a small number of assess the Penetration Aspiration score (P/A-VF) at
patients, the process has been repeated 20 times, in baseline and at 6 and 12 months (m) after treatment. All
order to prevent overfitting and detecting a range of RT plans were optimized to reduce dose to the
performance on a set of trained models. For each cycle SWOARs. Models of severe RILD were developed
the 4 best performing model have been evaluated. using dose to 9 SWOARs (superior, medium and inferi-
Finally the accuracy and k-statistics of each model have or constrictor muscle, SPCM; MPCM; IPCM; base of
been calculated and compared to HPV RNA test values. tongue, BOT; supra and glottic larynx, SL and GL;

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

parotid glands, PGs; cricopharyngeal muscle, CPM;


cervical esophagus, EC) and P/A-VF data at 6 and 12 m
B006

after treatment. A total of 72 features for each patient


were extracted (8 features for each SWOAR:
COULD FRACTIONATED IRRADIATION BE A

Dmin,Dmax,Dpeak,Dmean,V35,V45,V55,V65) and
POSSIBLE PARTNER FOR IMMUNOTHERAPY

analyzed with linear Support Vector Machine (SVM)


STRATEGIES IN CANCER TREATMENT?

and Bagged Tree Classification (BTC). Performances


AN IN-VITRO STUDY OF IMMUNOGENIC CELL

were evaluated computing the Area (AUC) under the


DEATH INDUCTION
L. Bardoscia1, F. Eckert2, L. Triggiani1-3,
Receiver Operating Characteristic (ROC) curve, esti- N. Pasinetti3-4, A. Colosini1-3, M. Buglione1-3,
mated in leave-one-out cross validation. Features were S.M. Huber2, D. Zips2, R. Bresciani5, S.M. Magrini1-3
ranked for importance using out-of-bag predictor 1Department of Radiation Oncology, Spedali Civili
importance estimates by permutation.
Hospital, Brescia; 2Department of Radiation Oncology,
Results: The relevance of SWOARs DVH features University Hospital Tuebingen; 3University of Brescia;
in predicting severe RILD emerged both at 6 and 12 m: 4ASST Valcamonica Esine, Brescia; 5Department of
AUC 0,82 with SVM and AUC 0,83 with BTC (6m); Molecular and Translational Medicine, Unit of
AUC 0,86 with SVM and 0,93 with BTC (12m). The Biotechnology, University of Brescia, Italy
SWOARs and the correspondent features with the high-
est importance to avoid severe RILD at 6 m resulted Aims: Immunogenic cell death (ICD) is one of the
BOT (V65 and Dmean), SPCM (Dmean), MPCM crucial steps of radiation-induced anticancer immune
(V45,V55;V65;Dpeak;Dmean;Dmax and Dmin), and response. Most publications argue in favor of hypofrac-
PGs (Dmean and Dpeak) whereas those with the high- tionated radiotherapy (RT), but several clinical settings
est importance at 12 m were MPCM (V55; Dmax and rely on normofractionated regimens and systematic
Dmean), IPCM (V55, V65 Dmin and Dmax) together analyses on fractionation sensitivity and radiobiological
with GL (V55 and Dmin), CPM (Dmin) and EC (Dmin) parameters are scarce in this field. We aimed to assess
(Figure 1). ICD induction systematically after different radiation
Conclusions: We have trained and cross validated a schedules using a biomathematical model.
NTCP model of severe RILD with a high discriminative Methods: A standard glioblastoma (GBM) cell line,
ability both at 6 and 12 m after RTCT. We expect to U87MG, and two patient-derived, stem cell enriched
improve the generalization capability of this model GBM cell lines, LKVII and LKXVII, were analyzed for
enlarging the number of training data with the ongoing in-vitro detection of damage-associated molecular pat-
prospective Italian Multicentric Study (NCT 03448341) terns (DAMPs) driving ICD: calreticulin (CRT) cell
in order to be suitable for clinical and planning deci- surface membrane exposure, high mobility group box1
sion-support. (HMGB1) extracellular release. CRT was assessed 24h
after single dose (2-24Gy) and daily fractionated RT
(5x2Gy, 5x3Gy, 5x4Gy). Percentage of CRT positive
cells after single dose RT was fitted with a non-linear
least square fit to a Hill function. We used the obtained
equation to calculate equivalent single fraction RT
doses for membranous CRT after fractionation.
HMGB1 confirmed ICD induction, normalized to num-
ber of viable cells 48h after single dose RT for U87MG
and LKVII.
Results: There was a vast difference in basal CRT
positivity in unirradiated controls (6.9±0.24% for
U87MG, 9.5±0.09% for LKVII, 15.3±0.18% for
LKXVII, respectively). All cell lines showed significant
ICD induction after ≥8Gy single dose irradiation and
5x3Gy and 4Gy. The data were well fitted by a Hill
function (R2>0.98). For both patient-derived cell lines,
10Gy normofractionation significantly increased CRT
membrane exposure. Corresponding single doses for
fractionated RT were higher for LKVII and LKXVII
compared to U87MG. Significant HMGB1 release was
observed for 8Gy irradiation in LKVII and 16Gy in
both LKVII and U87MG (8.9±0.9 pg/106 cells vs
21.1±1.5 pg/106 cells, 4.0±0.7 pg/106 cells vs
47.4±9.35 pg/106 cells, respectively).
Conclusion: Single doses of 8Gy or higher elicit
ICD as well as fractionated RT in GBM cells, a highly
radioresistant tumor entity. Daily fractionation seems to
cause cellular damage accumulation hence driving
Figure 1. Bootstrapped feature importance values for the variables included in the
NTCP model. The whiskers indicate the 95 percentile confidence intervals.

| 33 |
Selected Oral Communications

DAMPs release. A clinically low lethal dose 5x2Gy RTQA for future trials;
induces ICD in patient-derived, stem cell enriched cul- • research into novel treatment schemes or tech-
tures. Thus at least as the initial step of effective anti- niques, including proton and brachytherapy;
tumor immune response our findings may be the start- • validate the concept of prospective quality review
ing point to combine normofractionated RT and in RT.
immunotherapy strategies.
B008
B007
CORRELATION BETWEEN BODY MASS INDEX
QUALITY CONTROL IN PEDIATRIC RADIOTHERAPY: AND LATE TOXICITY IN ENDOMETRIAL CANCER
THE SIOPE-EORTC “QUARTET” PROJECT
G. Scarzello and L. Gandola, on behalf of SIOPe-
PATIENTS SUBJECTED TO ADJUVANT RADIO-

EORTC QUARTET Group


THERAPY WITH IMRT-IGRT TECHNIQUE
G. Terranova1, A. Palmeri1, G. De Gregorio1,
I.O.V.-I.R.C.C.S, I.N.T. A. Gioia1, G. Trapani1, A. Donofrio1, E. Quartuccio1,
V. Valenti1, G. Mortellaro2, G. Evangelista2,
High-quality RT, mostly in children, plays an essen-
A. Lo Casto1
tial role in achieving better outcomes reducing both
1Università degli studi di Palermo; 2ARNAS Civico Di
local recurrence and long-term toxicity. In May 2016 a
group of European experts in pediatric RT kicked-off Cristina Benfratelli, Italy
the project QUARTET (Quality and Excellence in Aims: Evaluation of Body Mass Index (BMI) and
Radiotherapy and Imaging for Children and correlation with toxicity in patients undergoing radia-
Adolescents with Cancer across Europe in Clinical tion treatment for endometrial cancer using IMRT-
Trials) in Brussels. QUARTET is assessing the quality IGRT technique.
and effectiveness of RT through an entirely online plat- Methods: 19 patients were analyzed after adjuvant
form: SIOPe and EORTC are joining forces in this ini- treatment with a dose of 50.4 Gy on pelvis and 45 Gy
tiative, the first for pediatric cancer in Europe, with the on lomboaortic lymphonodes from 2015 to 2018 for IB-
aim of improving RT through a centralized prospective
IIIC endometrial cancer. Patients were divided, accord-
review of treatment plans for every patient entered in
ing to their BMI, into 3 categories: normal weight (BMI
one of SIOPE’s trials. QUARTET started analyzing
18.5-24.9), overweight (BMI 25-29.9) and obese (BMI
patients treated for neuroblastoma, soon it will cover
greater than or equal to 30). We evaluated late toxicity
children and adolescents with rhabdomyosarcoma,
according to CTCAE 5.0 scale in patients with a median
renal and brain tumors (national initiatives are already
ongoing in Italy, Germany, France, UK, Scandinavia) follow-up of 24 months.
and successively it will include Hodgkin lymphoma, Results: Only one normal-weighted patient had G1
reaching an estimated number of 500 patients per year. GU toxicity and one G1 pelvic pain; among overweight
Supported by Fondatioun Kriibskrank Kanner, this pro- group one patient developed G2 GU toxicity; in the
ject is inscribed in the wider scope of the SIOPe obese group one patient had G1 GU toxicity and two
Strategic Plan “A European Cancer Plan for Children patients G1 GI toxicity. G1 pelvic pain was observed in
and Adolescents”, endorsed by the pediatric cancer two patients among this group.
community. The double ambition of QUARTET is to Conclusions: bmi greater than or equal to 30 is asso-
increase the cure rate of pediatric cancers and to ensure ciated with risk of late toxicity G1 gastrointestinal and
minimal side effects, which could potentially affect sur- G1 genito-urinary but in no case no g2 toxicity has been
vivors’ quality of life. QUARTET will ensure a central- found. Based on the toxicity recorded and considering
ized review by dedicated experts of prospective fields the low number of patients followed they need further
and radiation treatment plans for every child and ado- studies with larger population will clarify this report.
lescent before RT, in order to make necessary amend-
ments if needed. More specifically, the project will:
• develop standards for RTQA for pediatric tumors;
• report the inter-observer variability when following
the trial-specific delineation guidelines;
• apply existing TCP and NTCP models to estimate
variation in outcome from contouring variation;
• determine whether the outcome of the RTQA
benchmark case can predict the quality of RT;
• assess the quality of the RT, reporting the conformi-
ty and homogeneity index, and also the integral
dose delivered, looking to determine whether geo-
graphical location or treatment center size have any
impact on this;
• assess the cost-effectiveness of RTQA for the
respective cancer types and determining the role for

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

B009 B010
THE ROLE OF RADIOTHERAPY TREATMENTS IN STEREOTACTIC BODY RADIATION THERAPY IN
OLIGOMETASTATIC BREAST CANCER SETTING: UNRESECTABLE OLIGOMETASTATIC PATIENTS
PRELIMINARY ANALYSIS OF ADVANTAGE ON WITH LIVER LESIONS
A. Iurato, S. Palizzi, E. Ippolito, A. Di Donato,
P. Zuccoli, P. Falco, P. Matteucci, C. Di Venanzio,
PFS-2
T. Zinicola1, V. Masiello1, F. Marazzi1, S. Luzi1-2,
L. Boldrini1, G. Franceschini2-3, F. Moschella2, M. Marrocco, R.M. D’Angelillo, S. Ramella
D. Smaniotto1-2, S. Chiesa1, A. Petrone1, B Corvari1, Policlinico Universitario Campus Biomedico, Roma,
M. Balducci1-2, R. Masetti2-3, M.A. Gambacorta1-2, Italy
V. Valentini1-2
1Fondazione Policlinico Universitario A. Gemelli Aims: Evaluate outcomes of Stereotactic Body
IRCCS, UOC di Radioterapia Oncologica, Radiation Therapy (SBRT) in patients with liver metas-
Dipartimento di Diagnostica per Immagini, tases with oligometastatic disease.
Radioterapia Oncologica ed Ematologia, Roma; Methods: Unresectable oligometastatic patients
2Università Cattolica del Sacro Cuore, Istituto di with documented liver lesions were evaluated at our
Radiologia, Roma; 3Fondazione Policlinico institution for SBRT. Sites of primary tumor, size and
Universitario A. Gemelli IRCCS, UOC di Chirurgia prescribed dose for each lesion was recorded. The pre-
Senologica, Dipartimento di Scienze della Salute della scribed dose was modulated according to location of the
Donna e del Bambino e di Sanità Pubblica, Roma, Italy lesion and tolerance of the surrounding organs at risk:
lesions were treated with 3-8 fractions to a median total
Background: In the last years, thanks to diagnostic dose of 40.5 Gy (ranged from 30 to 62.5 Gy). Local
advantages and new target therapies, oligometastatic control (LC), Progression Free Survival (PFS) and
disease is an even more common presentation of cancer Overall Survival (OS) were evaluated using Kaplan
patients (pts). At the same time, oligoprogression is a Meier analysis.
reality too, that is raising the issue of maintaining sys- Results: Between 2010 and 2019, 54 metastatic
temic therapies that can be considered still efficacy. patients were treated at our institution with 58 total liver
Stereotactic body radiotherapy (SBRT) or Stereotactic lesions. Patients had a median age of 76 years (35-90
Radiosurgery (SRS) are emerging as part of years). Primary tumor was: colon-rectum cancer
oligometastatic disease in many tumours as prostate (46.3%), lung cancer (20.4%), breast cancer (9.3%) and
cancers. In this preliminary study, we analysed the role others (24%). Median tumor volume was 20.5 mm
of hypofractionated and SBRT/SRS radiotherapy in (range 7-56 mm). At a median follow-up of 7.87
breast cancer setting. months (range 0.83-112.93 months), Local Control
Material and Methods: All the patients with oligo- rates at 1 and 2 years was 75.2% and 59.3% respective-
progressive breast cancer (OPBC) during systemic ther- ly. Most common pattern of failure was in other sites of
apy that underwent hypofractionated VMAT, SBRT or liver. PFS at 1 and 2 years was 53% and 29.9% respec-
SRT were included into the study. Data on age, tumor tively with a median of 12.7 months. OS at 1 and 2
characteristics at diagnosis, systemic therapy, radiother- years was 75.2% and 59.3% respectively with a median
apy performed were retrospectively collected. of 28 months.
Progression free survival-2 (PFS-2) was defined as the Conclusions: SBRT is an effective therapeutic
time (months) from end of radiotherapy to new progres- option for treatment of liver metastases in unresectable
sion without changing systemic therapies. A Kaplan- oligometastatic liver disease, with a high local control
Meyer analysis was performed for PFS-2. rate.
Results: Eighteen pts were enrolled for this study.
Median age was 58 (35-86). Sixteen % of pts was IIIC
stage at diagnosis. Systemic therapies ongoing at the
moment of oligoprogression were: 50% anti-Her2
B011

drugs; 16,6% anti-CDK4/6 agents; 22% cytotoxic


VMAT TECHNIQUE RADIOTHERAPY IN LOCALLY
agents; 11,4% endocrine therapy. Radiotherapy was ADVANCED LUNG CANCER PATIENTS: RATE AND
administered with VMAT or SBRT/SRS FFF technique DEGREE OF LATE PULMONARY TOXICITIES IN
on brain (72.2% of pts) with a schedule of 50 Gy/5Gy,
30 Gy/3Gy or 25 Gy/8,5Gy; lung (16,6% of pts) with a
PATIENTS TREATED WITH CONCOMITANT

schedule of 50 Gy/10Gy; bone (11.2% of pts) with a


CHEMOTHERAPY
E. Molfese, M. Miele, A. Iurato, M. Fiore,
schedule of 30 Gy/6Gy. Mean PFS-2 was 10.63 months R.M. D’Angelillo, Lucio Trodella, S. Ramella
(1-25), with a positive trend of the Luminal subtype Università Campus Bio-Medico di Roma, Italy
respect Her2+ at chi-square test (CI=95%, p<.001).
Conclusion: Introducing focal hypofractionated Aims: To assess the rate and degree of observed late
/SBRT/SRS treatments in OPBC treatments, can pulmonary toxicity among locally advanced lung can-
improve PFS-2, prolonging sistemic therapies, espe- cer patients treated with VMAT technique and concur-
cially in good prognosis subtypes. Further studies are rent chemotherapy.
needed on large series to confirm these preliminary Methods: Locally advanced lung cancer patients
results, also with new target therapies ongoing. underwent concomitant radio-chemotherapy using

| 35 |
Selected Oral Communications

VMAT technique. After concomitant chemo-radiation Oncology/Medical University of Lublin; 31Cancer


treatment, all patients underwent periodic clinical and Institute of the Mediterranean; 32Treviso Hospital, Italy;
radiological follow-up: if occurred, radiation pneu- 33Haifa Hospital; 34University Hospital; 35CRLC Val
monitis was graded according to the National Cancer d’Aurelle; 36Hospital Agostino Gemelli; 37Santiago de
Institute Common Toxicity Criteria (vers.4.03). Chile Hospital; 38Medipol University; 39San Giovanni
Results: From January 2016 to December 2017, 38 Battista Hospital; 40IRCCS Istituto Tumori Giovanni
patients [median age 64 years (range 44-83)] underwent Paolo II; 41Okmeydani Research and Education
concomitant radio-chemotherapy with VMAT tech- Hospital; 42Hospital Universitario de Gran Canaria;
nique: 27 male (71%), 11 female (29%); histologically 43Tirol Kliniken; 44Tbilisi Cancer Center; 45SiChuan
24 adenocarcinoma (63 %), 8 squamous cell (21%), 6 Cancer Hospital
small-cell lung cancers (16%). Mean radiotherapy dose
delivered was 53,94 Gy using VMAT technique. With a Aims: A comprehensive collection and analysis of
median follow-up of 19.28 months, late pulmonary tox- clinical and technical data from 45 centres part of the
icity (CTCAE scale G=2) was reported in 2 patients International Society of Intraoperative Radiation
(5%), radiological pulmonary toxicity without symp- Therapy (ISIORT) was performed, in order to identify
toms (CTCAE scale G=1) occurred in 12 patients the range of IORT indications and techniques for the
(32%), 24 patients (63%) completed the treatment with- different tumour sites. The present study reports the
out pulmonary toxicity. results concerning the breast cancer.
Conclusions: In locally advanced lung cancer Materials and Methods: As of 2007, ISIORT partic-
patients, concomitant radio-chemotherapy using VMAT ipants collected in a common database demographic,
technique is a well tolerated treatment with acceptable
clinical and technical data related to IORT procedures.
lung toxicity. In order to spare organs at risk and obtain
Both prospective and retrospective data entry was
a better target coverage, VMAT technique can be used
with encouraging clinical results. allowed. The current study analyses 9.897 breast
tumours.
Results: According to all ISIORT registry collected
B012 data, 9.897 of all IORT procedures were performed on
patients with breast cancer. The median age of breast
patients was 62 years. There were 22 (0.2%) cases of
INTRAOPERATIVE RADIOTHERAPY (IORT) IN

male breast cancer treated with IORT. In 7.391 cases,


BREAST CANCER: ANALYSIS OF 9.897 CASES

IORT was performed with radical intent for primary,


FROM ISIORT DATABASE
C. Pisani1, F.A. Calvo2, F. Sedlmayer3,
newly diagnosed disease, while in 90 cases (0.9%) it
C. Schumacher 4, F. Cazzaniga5, M. Alessandro6,
A. De Paoli7, E. Russi8, M. Kruszyna9, R. Corvò10, was an attempt to rescue localized recurrent breast can-
F. Wenz11, R. Mazzarotto12, F. Fusconi13, cer. IORT was performed as a boost before or after
A. Ciabattoni14, R. Weytjens15, G. Ivaldi16, EBRT in 3.644 cases (36.8%) with doses of 4–12 Gy. In
A. Baldissera17, C. Leonardi1, V. Morillo18, 3.398 cases (34.3%), IORT was used as single radiation
M.F. Osti19, N. Bese20, G. Catalano21, treatment modality with doses of 7-21 Gy, mostly
A. Stefanelli22, C. Iotti23, L. Tomio24, V. Fusco25, between 18-21Gy (76.2%). Patients enrolled in study
I. Azinovic26, M. Aguilar27, F. Richetti28, protocols were 2.725; in detail, 1834 (67.3%) were
N. Kirsanova29, W. Polkowski30, A. Di Grazia31, treated with a single dose (18-21 Gy in 88.8% of cases)
A. Gava32, L. Abdach33, C. Vidali34, J.B. Dubois35, and 846 (31%) were treated with a boost dose. IORT
V. Valentini36, L. Badinez37, A. Altinok38, was delivered after and before tumour removal in
U. Ricardi39, A. Milella40, O. Alan41, P. Lara42, 71.9% and 19.6% of cases, respectively. In 8.714 cases
U. Ganswindt43, M. Topeshashvili44, J. Yin45, (88%), IORT was performed using electrons of 4-12
M. Krengli1 MeV energy. The patients treated with a 50-kV x-ray
1University Hospital of Piemonte Orientale; 2University
source were 763 (7.7%).
Hospital Gregorio Maranon; 3University Clinic for Conclusions: At present, the ISIORT database rep-
Radiotherapy; 4St. Elisabeth Krankenhaus; 5ASS resents the largest available clinical and technical IORT
Territoriale Papa Giovanni XXIII; 6Città di Castello data collection. Breast cancer is the most frequent IORT
Hospital; 7CRO; 8A.O. S. Croce e Carle; 9Greater treatment performed in the 45 centres taking part in the
Poland Cancer Centre; 10IST; 11University Medical study. This analysis shows that in most cases IORT on
Center; 12University Hospital; 13San Giovanni Battista
breast patients was used as a single shoot of 18-21 Gy,
City Hospital; 14Hospital San Filippo Neri; 15Wilrijk
Hospital; 16Hospital Istituti Clinici Scientifici Maugeri; the most employed treatment modality was electron
17AUSL Bellaria; 18Hospital Provincial de Castellón; beam and the procedure was most frequently performed
19University Hospital Sant’Andrea; 20Acibadem Maslak after the tumour removal. Only a minority of patients
Hospital; 21Multimedica Hospital; 22S. Anna Hospital; was included in clinical trials. These analyses could
23S. Maria Nuova Hospital; 24Santa Chiara Hospital; enhance the multi-institutional performance and serve
25Rionero in Vulture Hospital; 26Istituto Madrileño de as a basis for clinical trials design, in order to better
Oncologia; 27Clinica Biblica; 28Sacro Cuore Hospital; define the role of IORT in tailored multimodal thera-
29Almaty Cancer Center; 30Department of Surgical peutic approaches.

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

AIRO GIOVANI
Oral Communications

spine chordoma in terms of local control and lower late


effects. Aim of the study is to evaluate toxicity and qua-
C001

lity of life in young patients (pts) undergoing


PRELIMINARY EVALUATION OF LONG-TERM hadrontherapy for chordoma.
Methods: Between June 2012 and December 2018,
36 young pts with median age of 36 years (9-40) with
TOXICITY IN YOUNG PATIENTS WITH CHORDOMA

histologically proven chordoma, were treated with char-


TREATED WITH HADRONTHERAPY AT CNAO
E. Scipilliti1,2, E. D’Ippolito2, F. Cuccia2,3,
S. Durante2,4, S. Ronchi2, R. Petrucci2, M.R. Fiore2, ged particle therapy using active scanning beam deli-
F. Valvo2 very system at CNAO. We treated 22 skull-base chor-
1University Federico II School of Medicine, Department domas, 9 spine chordomas (level from C1 to L5) and 5
of Advanced Biomedical Sciences, Naples; 2Fondazione sacral chordomas (level S1-S3 and below). 17 pts were
CNAO, Centro Nazionale di Adroterpia, Pavia; treated with proton therapy (PT) median dose 74Gy
3Radiation Oncology School, University of Palermo; RBE (range 36-74) while 19 pts with carbon ion the-
4University of Milan, Department of Oncology and rapy (CIRT) with median dose 70.4Gy RBE (range 64-
Hemato-Oncology, Milano, Italy 73.6). We evaluated toxicity according to CTCAE v.4
and investigated QoL using EORTC QLQ-C30 que-
Aims: Chordomas are rare slow-growing tumors
stionnaires.
characterized by a locally aggressive growth pattern,
representing 50-60% of bone tumors. The 50–60% of Results: Median follow-up time was 26 months.
cases are localized in the sacrum-coccix followed by Late G3 toxicity was observed in 2 patients with skull-
skull-base (25–30%), cervical (10%) and thoracolum- base chordoma (carotid stenosis and seizures).
bar tract (5 %). The site of origin is commonly located Temporal lobe necrosis G2 was observed in 4 patients,
nearby organs performing important functions. The G1 in 2 patients. Six patients with spine/sacral chordo-
main treatment for chordoma is still represented by ma developed neurosensitive peripheral neuropathy: 3
radical surgery. In most cases the resection with wide patients experienced G1 toxicity, 3 patients G2 toxicity.
margins is complicated by severe dysfunctions. In No one showed bladder or bowel dysfunctions. No
young patients, in full social and working activity, the patient had walking impairment.
aggressive surgery is complicated by strong disabilities Conclusions: These data seem to confirm encoura-
with remarkable impact on their quality of life (QoL) ging results of hadrontherapy for chordoma especially
and socio-economics contribution. In the last decades in young patients, taking into account the lower late
particle therapy seems to be a safe alternative to radical severe side effects compared to the disabilities expected
surgery in sacral chordoma, and the best radiotherapy from aggressive surgery. All patients were able to keep
technique in post-operative treatment of skull-base and working and having a normal social life after treatment.

| 37 |
Oral Communications

damage to surrounding healthy tissues. For this reason,


it is a feasible and effective therapeutic option also for
C002

young patients with functional and benign brain disea-


ses and it ameliorates their QOL without severe toxici-
LONG-TERM QUALITY OF LIFE AND TOXICITIES

ties.
IN YOUNG PATIENTS (<=35 YEARS OLD)
TREATED WITH STEREOTACTIC RADIOTHERAPY
(SRT) FOR FUNCTIONAL AND BENIGN BRAIN
DISEASES
S. Lillo1, C. Vadalà1, R.E. Vadalà1, F. Arena1,
C003

A. Cacciola1, D. Cambareri1, L. Campanelli1, G.R.


Chisari1, V. Davì1, L. Molino1, I. Napoli1, S. Parisi1,
ITALIAN RESULTS OF AN INTERNATIONAL SUR-

C. Severo1, C. Tamburella1, A. Pontoriero1, G. Iatì1,


VEY ON ELECTRONIC PATIENT-REPORTED OUT-

A. Santacaterina2, S. Pergolizzi1
COMES (EPRO) BY THE EORTC YOUNG

1Radiation Oncology Unit - Department of Biomedical,


RADIATION ONCOLOGY GROUP.
L. Visani1, I. Meattini1, I. Desideri1, M. Fiore2,
Dental sciences and Morphological and Functional A.N. Abrunhosa-Branquinho3, S. Adebahr4,5,6
Images, University of Messina; 2Azienda Ospedaliera E. Clementel7, R. Ciervide8, Y.G. Eller9, S. Hafeez10,
Papardo, Messina, Italy B. Hoeben11, O. Kaidar-Person12, I. Kindts13,
F. Mehrhof14, C. Mercier15, D. Nevens16, L. Ollivier17,
Aims: Advanced radiotherapy techniques, such as C. Ostheimer18, M.H. Suppli19, H. Zhu20,
Stereotactic Radiotherapy (SRT), represent effective E. Rivin del Campo21, A.H. Thieme14
treatment modalities both for those benign brain 1Radiation Oncology Unit, Azienda Ospedaliero
tumours whose complete surgical resection is impossi-
ble or associated to high risk of sequelae and for func- Universitaria Careggi, University of Florence,
tional brain diseases in which alternative therapeutic Florence, Italy; 2Campus Biomedico, Radiation
choices have failed. The aim of this study is to assess Oncology, Rome, Italy; 3Centro Hospitalar Lisboa
the long-term quality of life (QOL) and the late toxici- Norte - E.P.E. - Hospital Santa Maria, Department of
ties in young patients treated with SRT for functional Radiation Oncology, Lisbon, Portugal; 4Department of
and benign cerebral diseases. Radiation Oncology, University Medical Center
Methods: From July 2007 to February 2019, 46 Freiburg, Freiburg, Germany; 5German Cancer
young patients (<=35 years old) with functional and Consortium (DKTK) Partner Site, Freiburg, Germany;
6German Cancer Research Center (DKFZ), Heidelberg,
benign cerebral diseases including arteriovenous
malformation (22), meningioma (9), vestibular schwan- Germany; 7EORTC Headquarters, Brussels, Belgium;
8Department of Radiation Oncology, HM Hospitales –
noma (8), craniopharyngioma (3), pituitary adenoma
(2), hemangioblastoma 1 and trigeminal neuralgia 1 Hospital de Sanchinarro, Madrid, Spain; 9Department
were treated with SRT. They were 54% female and 46% of Radiation Oncology, University Hospital of Bern,
male, and median age at diagnosis was 28 years (range Bern, Switzerland; 10Institute of Cancer Research - The
8-34 years). The median follow-up time from treatment Royal Marsden NHS Foundation Trust, Radiotherapy
was 73 months (range 4-140 months). Subjects have and Imaging, London, United Kingdom; 11Department
been surveyed using the Spitzer QOL-Index (SQLI) to of Radiation Oncology, Radboud University Medical
investigate the quality of life, and the Radiation Center, Nijmegen, The Netherlands; 12Oncology
Therapy Oncology Group (RTOG) scale was used to Institute, Radiation Oncology and Neuroncology Unit,
assess late radiation therapy-related toxicities. Rambam Medical Center, Haifa, Israel; 13KU Leuven,
Results: At baseline, 38/46 patients (83%) were University Hospitals Leuven, Lab of Experimental
Radiation Oncology, Belgium; 14Department of
symptomatic: 24 headaches, 6 hearing disorders and
Radiation Oncology, Charité - Universitätsmedizin
dizziness, 5 motor disorders, 2 visual disorders with
Berlin, Berlin, Germany; 15University of Antwerp,
endocrinological symptoms, and 1 facial pain.
Molecular Imaging, Pathology, Radiotherapy &
Headache was resolved in 70%, improved in 10%,
Oncology (MIPRO), Antwerp, Belgium; 16Department
unchanged in 20%; hearing disorders and dizziness
of Radiation Oncology, Iridium Cancer Network,
remained unchanged in 82% and reduced in 18%; both
Wilrijk, Antwerp, Belgium; 17Radiation Oncology
patients with pituitary adenoma assisted to a successful
Department, University Hospital, Brest, France;
reduction of ACTH secretion; a reduction in facial pain 18Department of Radiation Oncology, University
was observed too. As suggested by these data and con-
Hospital Halle, Halle, Germany; 19Department of
firmed by the SQLI<=8, compared to pre-SRT more
Oncology, Rigshospitalet, Copenhagen University
than half of the symptomatic subjects (21/38) reported
Hospital, Copanhagen, Denmark; 20Department of
an improvement in the global health status after treat-
Radiation Oncology, Fudan University Shanghai
ment. Regarding SRT toxicities, no patients reported Cancer Center, Shanghai, China; 21Department of
visual deficit worsening, new motor or cranial nerves Radiation Oncology, Tenon University Hospital,
deficits and new hemorrhages, with a RTOG<=1. Sorbonne University, Paris, France
Conclusions: SRT provides a good local response
while being reasonably safe as it facilitates the delivery Aims: Patient reported outcomes (PROs), defined
of high-dose radiation to increasingly limited target as direct expressions of patients’ health status without
volumes with a low risk of functional radiation-related the interpretation of a clinician, have been shown to be

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

clinically significant to assess adverse events (AEs)


related to radiation therapy (RT). As part of the deve-
C004

lopment of an application to evaluate electronic PROs


(ePROs), the young Radiation Oncology Group
DEEP INSPIRATION BREATH HOLD

(yROG) of the European Organisation for Research and


RADIOTHERAPY: INNOVATIVE ORGAN

Treatment of Cancer (EORTC) conducted an internatio-


PRESERVATION TECHNIQUE. OUR EXPERIENCE
I. Nuzzo1, S. Falivene2, V. Nardone2, M. Mormile2,
nal survey to evaluate the use and perceived benefits of A. Di Biase2, F.M. Giugliano2, L.P. Posimo2,
PROs, and to rank desirable features for the ePRO tool. S. Guerriero2, F. Lepone2, S. Maffei2, S. Cappabianca1,
Methods: The survey was addressed to professio- C. Guida2
nals (physicians, radiation therapists, nurses) regularly 1Department of Precision Medicine, University of
involved in treating patients with RT. The questionnaire Campania Luigi Vanvitelli, Napoli; 2Unit of Radiation
included 40 items and rated ePRO tool features on a 5- Oncology Ospedale del Mare, Napoli, Italy
point bipolar Likert scale, ranging from 1 (very unim-
portant) to 5 (very important). Aims: To match treatment planning in free
Results: From July 2018 to December 2018, 354 breathing (FB) vs deep inspiration breath hold (DIBH)
valid replies from 26 countries worldwide were collec- for patients with left side breast cancer valuating dosi-
ted, 47 (13.3%) of which from Italy (IT), the second metric difference to heart, left anterior descending
most participative country after Germany (24.3%). artery (LAD) and ipsilateral lung .
Most Italian participants were radiation oncologists Methods: Thirteen patients with left breast carcino-
(95.7%), mainly working in university hospitals ma and candidate to radiotherapy were enrolled conse-
(87.2%). The PROs utilization rate among Italian cutively from 01/12/2018 to 15/02/2019. A CT scan in
respondents was 59.6%, the highest value reported FB, the study of respiratory motion and then a DIBH
[international (int) rate 42.4%; p=0.03]. PROs were TC were performed for all patients. During DIBH TC it
considered important for RT treatment [int average was used SentinelTM to have a reference surface.
(avg) 4.1 points (pts); IT avg 4.3 pts; p=0.11], leading Gating window was initially defined as 4 mm and then
personalized on respiratory study. For visual feedback
to a higher accuracy of AE assessment (int avg 3.6 pts;
of the breathing position, the patients wear video glas-
IT avg 3.9 pts; p=0.022). Only a small proportion of
ses Epson Moverio BT200. During DIBH treatment it
respondents used ePROs in their clinical practice (int
was used CatalystTM and portal imaging with
avg 27.2%; IT avg 36.2%; p=0.013), although nearly all
iViewTM to evaluate target position. Tangential fields
of them (IT 97.9%; int 96.9%) would regularly use
were used with field in field technique to optimize the
ePRO if available. The highest ranked feature for an dose distribution. Hypofractionated schedule of 20 frac-
ePRO tool in Italy was ease-of-use by patients (int/IT tion was used. Medium dose, V25, V10, V5 of heart,
avg 4.7 pts). Benefits of ePROs ranked more appropria- average dose and V20 of LAD, V20,V10, V5 of ipsila-
te in the setting of curative patients (int avg 4.5 pts; IT teral lung were valuated. A subgroup analysis of respi-
avg 4.6 pts). The highest ranked cancers to benefit from ratory cycle excursions was done in order to identify a
ePRO were head and neck (total avg 4.5 pts; IT avg 4.6 population with a possible benefit. It was considered
pts) and gastrointestinal (int avg 4.2 pts; IT avg 4.4 pts). variation of β/α (α=max excursion FB; β=min excur-
Conclusions: Among Italian respondents, PROs uti- sion DIBH) choosing arbitrarily a cut-off of 3.5. The
lization was higher than internationally, still identifying time of the individual sessions for each patient was cal-
room for improvement regarding the usage of ePRO culated and analysed at the start and 4 time until the end
tools. This survey indicates a high demand for ePROs in of treatment.
the field of radiation oncology. An app to assess PROs
for RT-related AEs was successfully created and its
design will be adapted to better satisfy the users’ expec-
tations.
Table 1.

Results: All 13 patients were treated with DIBH


with good compliance and no interruption. The mean

| 39 |
Oral Communications

heart dose was 2.69 Gy in FB vs 1.44 Gy in DIBH with RT due to systemic disease progression and late toxicity
an average reduction of 46%. The mean LAD dose was was not evaluated. Only one acute hematologic G3
10.13 Gy in FB vs 4.96 Gy in DIBH with an average toxicity was registered (which required one-week treat-
reduction of 52%. Analyzing DVHs the mean values of ment interruption) and two G3 epithelial toxicities.
V5, V20 and V25 at the heart and V20 at the LAD were Only one patient developed a grading≥3 late toxicity.
decreased with the DIBH vs FB (Tab 15). The exposure She was treated with SIB to a PET positive LN near the
of the ipsilateral lung dose were analyzed. The analysis right ureter and later developed a right hydro-nephrosis
by subgroup showed that 4 patients had an excursion requiring surgery to re-implant the right ureter into the
with a β/α<3.5 related to variation of dosimetric para- bladder. Histological examination demonstrated the
meters at the heart (V20 and V25) and LAD (Dmax and complete response of the tumour. With 3 years of fol-
V20) not statistically significant. The timing analysis low-up, local control was 86% and distant progression
shows a decreasing execution time (from 20 min at T1 was registered in 28% of pts. Seventy-six % of pts were
to 10 at T4). alive at the last follow-up, all with disease control.
Conclusions: DIBH is an excellent heart-saving Conclusions: IG-IMRT in the treatment of young
technique, allowing adequate coverage of the target and pts with gynecological cancer is safe with a very low
without major obstacles in timing management in a rate of acute and late ≥G3 toxicities, and with good out-
modern radiotherapy department. comes even in advanced disease and pts not suitable for
brachitherapy boost.

C005
Table 1.
TOXICITIES AND OUTCOMES IN YOUNG
GYNAECOLOGICAL CANCER PATIENTS TREATED
Toxicity G0 G1 G2 G3 G4
WITH IMRT
F. Borroni1,2, A. Fodor1, C.T. Delle Curti1,2, Acute GE 20% 52% 28% 0 0
A. Sanchez Galvan1,2, R. Tummineri1,2, Late GE 79% 21% 0 0 0
C.L. Deantoni1, F. Zerbetto1, A. Deli1, P. Mangili3, Acute GI 34% 39% 27% 0 0
L. Perna3, S. Arcangeli2, N.G. Di Muzio1 Late GI 90% 5% 5% 0 0
1Department of Radiotherapy, San Raffaele Scientific Acute GU 48% 43% 9% 0 0
Institute, Milano; 2Department of Radiotherapy, Late GU 90% 0 5% 0 5%
University of Milano-Bicocca; 3Medical Physics, San Acute Hematologic 71% 10% 14% 5% 0
Raffaele Scientific Institute, Milano, Italy Late Hematologic 58% 42% 0 0 0
Acute epithelial 38% 33% 19% 10% 0
Aim: To evaluate toxicity and outcomes in young Late vaginal stenosis 58% 16% 26% 0 0
patients (pts) with gynaecological cancers treated with
Image-Guided Intensity Modulated Radiotherapy (IG-
IMRT) in our institution.
Material and method: From 09/2007-02/2018 21 pts
≤ 40 year old with gynaecological cancers (16 uterine
C006
cervix, 2 ovarian, 1 vulvar and 2 endometrial) were
treated with adjuvant (n= 13) or radical (n=8) IG-IMRT.
DYSGEUSIA AND NAUSEA DURING AND AFTER

Median age was 35.7 (21-40) years. Neoadjuvant che-


RADIOTHERAPY IN HEAD AND NECK CANCER

motherapy (CHT) was prescribed in 7 pts (all pts recei-


PATIENTS
G.C. Iorio1, S. Martini1, F. Arcadipane2, V. De Luca1,
ved paclitaxel-carboplatin), concurrent CHT in 9 pts (7 F. Olivero1, A. Gastino1, P. Silvetti1, U. Ricardi1,
pts weekly cisplatin, one patient daily capecitabine and P. Franco1
one patient cisplatin- 5FU). Fifteen pts were treated 1University of Turin, Department of Oncology-
with helical IMRT and 6 pts with volumetric arc IMRT.
Radiation Oncology, Turin; 2Città della Salute e della
Pelvic +/- lumbar- aortic (LA) LN planning target volu-
Scienza, Department of Oncology-Radiation Oncology,
me (PTV) and tumour PTV median dose prescription
Turin, Italy
was 50.4 (50-55) Gy in a median of 28 (25-28) fr.
Exclusive mediastinic and / or LA chains were treated Aims: Dysgeusia and nausea are common adverse
in 3 pts to 50.4 Gy. Seven pts received a simultaneous events occurring when treating Head and Neck cancer
integrated boost (SIB) on PET positive LN with dose (HNC) patients with radiotherapy (RT). As consequen-
ranging from 60.4 to 63.2 Gy and one patient 60 Gy to ce, patients’ Quality of Life and treatment-compliance
parameters. Six pts were treated with brachytherapy can result severely affected. The aim of the present
boost (12 Gy/2fr-30 Gy/6 fr), and 3 with external beam study was to prospectively evaluate dysgeusia, during
boost (15 Gy/3 fr-24 Gy/12 fr). treatment and follow-up, using the chemotherapy-indu-
Results: Median follow-up is 37.5 (1.8-138.5) ced taste alteration scale (CiTAS), a metrics based on
months. Acute and late gastro-enteric (GE), rectal (GI), 18-items exploring three dimensions (quantitative and
urinary (GU), hematologic and epithelial toxicities are qualitative changes in taste perception, and diet-related
included in Table 1. Two pts died after 2-4 months after issues) identified through a four-factor analysis: decline

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

in basic taste, discomfort, phantogeusia–parageusia,


and general taste alterations. Herein we report a further
C007

update, at 1 year, of Our analysis.


Methods: Between 2016 and 2018, 31 HNC
STAGE I TESTICULAR SEMINOMA:

patients were treated with Volumetric Modulated Arc


OUR EXPERIENCE OF RADIOTHERAPY

Therapy (VMAT) within a definitive or adjuvant setting


FOR <40 YEAR-OLD-PATIENTS
R. Marchese, G. Lazzari, M. Soloperto, A.R. Marsella,
(RT or CMT, 6 or 7 week overall treatment time). As A.M. Crastolla, S. Devicienti, M.G. Monis,
well, we scored, according to Common Toxicity G. Porrazzo, M.L. Clarizio, A. De Zio,
Criteria Adverse Events, nausea and other treatment- C.M. Malcangi, G. Silvano
related toxicities. We prophylactically employed a gin- Struttura Complessa Radioterapia Oncologica, Presidio
ger-based supplement named Naumix/Naugin Ospedaliero San Giuseppe Moscati, Taranto, Italy
(Gamfarma, Milan, Italy), to potentially mitigate both
nausea and taste impairment. Introduction and aims: Radiotherapy (RT) and che-
Results: Using the CiTAS scale, we highlighted a motherapy represent adjuvant options for testicular can-
progressive increase in all dysgeusia dimensions, cer which is the most common solid cancer in males
peaking at the VII week of treatment and a subsequent between 20 and 40 years of age. After radical inguinal
partial late recovery. In particular, we observed a reco- orchiectomy, surveillance is the preferred approach for
very for discomfort, phantogeusia–parageusia, and pT1-pT3 tumors but there is a risk of locoregional
general taste alterations at 6 and 12 months (see details lymph node micrometastases of 20% if no adjuvant the-
in Figure 1). Grade 2 nausea, observed to be as low as rapy is administered, especially for tumor size of 4 cm
12.9% potentially due to the use of ginger, peaked at the or more and invasion of the rete testis. During the past
III week of treatment. Of interest, for patients experien- years RT treatment fields were larger and radiation
cing G1–G2 nausea a significant correlation was found doses were higher than those currently used causing
with the score of the dysgeusia dimension of discomfort inacceptable side effects. Our study aims to evaluate
(II-VI week of treatment, p<0.05). efficacy and toxicity of limited-volume and low-dose
Conclusions: Our prospective clinical data point out lymph node RT for <40-year-old patients with stage I
the multidimensional pattern of dysgeusia and its trend testicular pure seminoma.
during RT or CMT in HNC patients. The prophylactic Methods: Between 2005 and 2014, thirty young
use of ginger may have limited the number of patients patients (<40 years) with stage I seminoma were treated
experiencing clinically significant nausea and, suppo- at Radiotherapy Department in Taranto. Median age
sedly, reduced taste impairment. Further analyses (2- was 30 years (range between 18 and 37 years). All
patients underwent orchiectomy and received histologi-
years follow-up) are planned in the close future.
cal diagnosis of pure seminoma, no patient received
chemotherapy. RT was delivered using opposed antero-
posterior and posteroanterior fields and RT fields exten-
ded from the superior border of T11 vertebral body to
the inferior border of the L5 vertebral body +/- renal
hylum. Until 2007 RT was delivered with a total dose of
25.2 Gy (1.8 Gy per fraction) and from 2008 with a
total dose of 20 Gy (2 Gy per fraction). Acute and late
gastrointestinal and genitourinary toxicities were eva-
luated. Relapse rate, Disease Free Survival (DFS) and
Overall Survival (OS) were calculated.
Results: Median follow-up was 8.5 years. Forty-
three percent (43.3%) of patients were treated with
paraaortic RT while the remaining part was treated with
paraaortic RT plus renal hilum RT. Acute toxicity was
mainly digestive, 36.6% of patients presented acute
mild/moderate nausea and one patient diarrhea. No
acute genitourinary toxicity was observed. No late toxi-
cities were observed. No local relapse and no distant
Figure 1. CiTAS Scale Trend.

metastases were observed. One patient experienced


controlateral testicular cancer and he was successfully
treated with surgery and chemotherapy. DFS and OS
were 100% since all patients were alive in complete
remission at last controls.
Conclusions: Our ten-year experience on young
patients showed that limited-field and low-dose RT
represents a valid option for stage I testicular seminoma
with acceptable toxicity and excellent results in terms
of disease control and survival rates.

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Oral Communications

C008 C009
PEDIATRIC BRAINSTEM CANCER: A RETROSPEC- EVALUATION OF RADIATION PULMONARY TOXI-
TIVE STUDY ON OVERALL SURVIVAL CITY PROBABILITY IN LEFT-SIDED BREAST
C. Scoglio1, K. Sayad1, R. Grassi2, A. Maiorana1, RADIOTHERAPY: A COMPARISON BETWEEN
L. Mastrandrea1, G. Scimone2, D. Di Gennaro2 VMAT AND FIELD-IN-FIELD (FIF) TECHNIQUES
Università degli Studi della Campania Luigi Vanvitelli, F. Rottoli, L. Grimaldi, V. Morandini, S. Berlinghieri,
Azienda Ospedaliera Universitaria S. Giovanni di Dio e E. Castrezzati, L. Spiazzi, P. Frata, N. Pasinetti
Ruggi D'Aragona, Napoli, Italy Department of Radiation Oncology, ASST Valcamonica,
Esine, Brescia, Italy
Aims: Brainstem tumors are the second most com-
mon form of cancer in children under the age of 15 Aims and scopes: Purpose of this work is to compa-
(after leukemia) and the second cause of cancer death. re the risk of radiation-induced pulmonary toxicity in
The brainstem cancer treatment is still an open challen- the treatment of the left breast irradiated using VMAT
ge, due to possible and severe acute side effects, such as or FIF technique.
respiratory failure. Specifically, radiotherapy (RT), Materials and Methods: 10 patients undergoing left
generally associated with chemotherapy, is fundamental breast radiotherapy were evaluated: the estimate of pul-
for the standard of care, trying to improve quality of life monary toxicity, with the relative serial model, had a
and increase overall survival (OS). In our center from range from 0.0% to 61%. Two treatment plans were
March 2009 to May 2019 were treated eleven pediatric optimized for every patient, one with FIF technique
patients, aged between 5 and 15, with diagnosis of ana- (2Gy/fr x 25fr, boost 2Gy/fr x 5fr) and one with VMAT
plastic astrocytoma, glioblastoma and diffuse glioma, (1.8Gy/fr x 28 fr, SIB 2.1Gy/fr x 28 fr).The fractiona-
with brainstem localization. In this retrospective study tion schemes were chosen to keep, as possible, the same
we report data relating to OS and relapse-free survival BED values both on the target and the organs at risk.
(RFS). EQD2 was calculated from the dose absorbed by the
Methods: The diagnosis of this class of tumors was lungs (both ipsilateral and contralateral) and then the
achieve by imaging/biopsy. All patients had performed Relative Seriality model for radiation pneumonitis was
brain CT and MRI with and without contrast pre-treat- used as method to evaluate the probability of pulmo-
ment. All patients underwent concomitant chemiothe- nary toxicity for both lungs (Grade1-2: α/β=3Gy,
rapy (nimotuzumab and vinorelbine or temozolomide) s=0.15, D50=16.3Gy, g=1.08; Grade 3-4: α/β=3Gy,
s=0.01, D50=30.1Gy, g=0.97).1
and RT with VMAT on VersaHD by Elekta, previously
immobilized with custom systems.
Results: The performance status was by 0 to 2 and
all patients were symptomatic at diagnosis. RT was con-
tinuously delivered at conventional fractionation of 1.8
Gy for fraction (fx), at dose of 54 Gy in 30 fx in 6
patients, at dose of 59.4 Gy in 33 fx in 4 patients. One
patient at dose of 43.2 Gy (24 fx) stopped RT for pul-
monary toxicity G4; he resumed at the resolution of the
interstitial pneumonia, reaching the dose of 63 Gy. No
other G1-G4 toxicity was reported. After the treatment
all the patients had an improvement of the initial symp-
toms and all were eligible to perform sequential che-
motherapy. The median OS, calculated from the time of
diagnosis, was 11 months (range from 1-47 months).
Eight patients had local relapse. The median RFS was
10 months (range 2-31 months). At progression disease
(PD) only 5 patients performed re-irradiation, 3 patients
at doses of 19.8 Gy in 11 fx, 1 patients at the dose 36
Gy in 20 fx and 1 at doses of 18 Gy in 10 fx. Of the 11
patients enrolled in the study, 6 patients are still alive
Figure 1.

without evident signs of toxicity, included in a regular


program of follow-up. Results: The probability of developing pulmonary
Conclusions: Based on our experience, despite the toxicity increases in contralateral lung when using
risk of severe acute side effects, the radiotherapy prove VMAT (Figure 1), although these probability values are
to be a valid option to challenge brainstem tumors with very low. Instead in ipsilateral lung the pulmonary toxi-
a discrete tolerability profile. city probabilities, either of Grade 1-2 or of Grade 3-4,
are lower with VMAT respect to FIF technique. Some
correlations between pulmonary toxicity and Dose
Volume (DV) parameters have been found: they depend

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

of the toxicity Grade but are independent of the techni- Results: The 6MWT improved by 33.83m (+ 7% of
que used (Figure). By choosing the acceptable probabi- predicted) in the CA and worsened by 22m (-7% of pre-
lity value, it is possible to find DV constraints in terms dicted) in the CO, with a difference higher than 55m.
of V20Gy for toxicity of Grade 1-2 and V15Gy for toxi- Regarding fatigue during exertion, the final average
city of Grade 3-4. score reduced by 0.6 in CA and increased by 1 in CO.
Conclusions: Among the side effects of the left For dyspnea, a slight deterioration was observed in the
breast irradiation the pulmonary toxicity, both of Grade CA (+ 0.3) and worsening of greater intensity in CO
1-2 and Grade 3-4, has to be carefully evaluated. In our (+1). Quality of life worsened in both groups. On the
study, VMAT increases the probability of pulmonary other hand, the lung function tests did not show any
toxicity for the contralateral but not for the ipsilateral significant changes.
lung. A cautious evaluation of the irradiation technique Conclusions: The exercise capacity and the fatigue-
is therefore recommended. dyspnea pairing improved in the cases, while the respi-
ratory function and quality of life seem to remain
unchanged during the 8 weeks of radiotherapy and H-
Reference RH treatment. To our knowledge this is the first report
1. A. Tzikas, G. Komisopoulos, B. C. Ferreira, S. Hyödynmaa, about the use of a H-RH program in patients treated
S. Axelsson, N. Papanikolaou, E. Lavdas, B. K. Lind, P. with high dose lung RT. Even if the number of patients
Mavroidis, Radiobiological Evaluation of Breast Cancer is limited it appears an innovative approach in order to
Radiotherapy Accounting for the Effects of Patient improve respiratory function of these kind of pts.
Positioning and Breathing in Dose Delivery. A Meta Analysis
Technol Cancer Res Treat. 2013 Feb;12(1):31-44 This study is still ongoing on a selected group of
patients treated with radical chemoradiation.

Table 1.
C010
HOME RESPIRATORY TRAINING IN PATIENTS
UNDERGOING RADIATION THERAPY FOR LUNG
CANCER
G. Volpi1, D. Greco1, J. Branz2, R. Buraschi2,
S. Pancera2, A. Premi1, E. Ranghetti1, E. Salah1,
S. Negrini2, S.M. Magrini1, P. Borghetti1
1Radiation Oncology Department, ASST Spedali Civili

and University, Brescia; 2IRCCS Foundation Don


Gnocchi Miano and University of Brescia, Italy
Aims: The prevention and minimization of pulmo-
nary toxicity is a very important goal for patient who
C011

perform radiation therapy for lung cancer. Respiratory


rehabilitation in thoracic oncology is often indicated
PRELIMINARY ANALYSIS OF ANXIETY EVALUA-

after surgery, while there is no evidence about its use in


TION IN RADIOTHERAPIC PATIENTS
V. Nardone1, F. Scala2, M. Gaetano1, L. Zaccagnino1,
radiotherapy. The aim of the study is to evaluate the A. Di Gennaro2, S. Maffei1, M. G. Calvanese1,
effectiveness, in terms of exercise capacity, dyspnea A. Di Biase1, S. Cappabianca2, C. Guida1
and fatigue, quality of life and respiratory function, of a 1Radiation Therapy Unit, Ospedale del Mare ASL Na1,
home rehabilitation (H-RH) program in patients under- Napoli; 2Department of Precision Medicine, University
going radiation therapy for lung cancer. of Campania Luigi Vanvitelli, Napoli, Italy
Methods: From March 2018 to May 2019 23
patients, 12 “cases” (CA) and 11 “controls” (CO), were Aim: To evaluate anxiety of patients undergoing
considered for a H-RH program in a single Institution. radiation therapy.
The preliminary evaluation was conducted on 12 Methods: We included all the patients undergoing
patients (8 CA and 4 CO). Severe cardio-circulatory radiation therapy at our Department in four days, each
diseases, orthopedic and neurological problems or ina- a week for a month. All the patients that gave their con-
bility to understand the instructions were considered as sent were asked to fulfill a validated questionnaire
exclusion criteria. All patients were treated with high- (STAI-Y, State trait anxiety inventory scale) and the
dose radiotherapy (adjuvant or radical). Patients featu- Anxiety thermometer (from 0 to 10 score). We took into
res are described in the Table 1. The 8 cases underwent account also sex, age, week of radiation treatment and
an 8-week training program (5 days a week), while the disease. For the STAI-Y we considered as cut-off 40 to
controls did not. All patients were evaluated, before RT, detect clinically significant anxiety, whereas the ther-
by 6-minute walking test (6MWT), Borg scale, SF-36 mometer was analysed as a continuous variable. We
health questionnaire and respiratory function test. calculated the differences in anxiety scales for the clini-
These tests were repeated at the end of the treatment. cal variables (sex, age, disease, week of treatment) with
Each patient had a self-compilation chart for monito- Chi-square test (for STAI-Y) and with Anova test (for
ring dyspnea and fatigue during exercise. Anxiety thermometer).

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Oral Communications

Results: We included 198 patients (108 males and


90 females), with a median age of 65 years (mean 64,8
C012

years, range 34-84 years). STAI-Y median score was 39


(mean 39,4, range 19-71), 100 patients (50,5%) showed
INOPERABLE PELVIC SIDEWALL RECURRENCE

a STAI-Y <40 and 98 patients showed a score ≥40


OF GYNECOLOGICAL CANCER TREATED WITH

(49,5%), whereas the median score of Anxiety thermo-


PARTICLE THERAPY: CNAO PRELIMINARY

meter was 4 (mean 3,8, range 0-8). There were no dif-


EXPERIENCE
A.Barcellini1, V. Vitolo1, R. Lazzari2, L. Cobianchi3-4,
ferences among sex (p:0,483), whereas patients at the R. Biffi2 , A. Facoetti1, M.R. Fiore1, B. Vischioni1,
first week of treatment showed the highest anxiety (for A. Iannalfi1 , M. Bonora1, S. Ronchi1, R. Petrucci1,
both test, p<0,001). Taking into consideration the diffe- E. D’Ippolito1, G. Viselner1, C. Laliscia5, A.
rent disease, the patients showing highest anxiety were Gadducci6, S. Durante17, F. Cuccia1,8, E. Scipilliti1,9,
head and neck cancer patients (75% patients showing A. Mirandola1, A. Vai1, E. Mastella1, L Preda1-4,
STAI-Y>40), followed by brain cancer patients (66%), F. Valvo1
lung cancer (50%), gastrointestinal cancer (41%), brea- 1National Center of Oncological Hadrontherapy
st cancer (35%) and prostate cancer (15%), p<0,001. (CNAO), Pavia; 2European Institute of Oncology,
Conclusions: Anxiety evaluation in patients under- Milan; 3General Surgery Department, Fondazione
going radiation therapy is higher than expected. These IRCCS Policlinico San Matteo, Pavia; 4Department of
measurements could be useful in order to start medical Clinical-Surgical, Diagnostic and Pediatric Sciences,
humanities programs with the aim of decreasing anxiety University of Pavia; 5Department of New Technologies
scores. and Translational Research, Division of Radiation
Oncology, University of Pisa; 6Department of
Experimental and Clinical Medicine, Division of
Gynecology and Obstetrics, University of Pisa;
7University of Milan, Division of Hematology and

Hemato-oncology, School of Radiation Oncology,


Milan; 8University of Palermo, School of Radiation
Oncology, Palermo; 9University Federico II of Naples,
School of Medicine, Department of Advanced
Biomedical Sciences, Naples, Italy
Aims: Pelvic recurrences of gynecological cancer
are generally resistant to RT/chemotherapy and most of
these women need to take into consideration the possi-
bility that normal tissues (such as bowel) might receive
a high cumulative dose. For their biological and physi-
cal characteristics particle therapy (PT), with protons
and carbon ions (CI), could be an interesting alternative
treatment with curative intent. The aim of the current
study was to evaluate the feasibility, acute toxicity and
early clinical outcome of PT in patients (pts) with pel-
vic sidewall recurrence (PSWr) of gynecological
tumors.
Methods: Between May 2014 to May 2019, 11
Figure 1.

patients (median age 56) with PSWr within or at the


edge of the previously irradiated field were treated
using PT. They had recurrence of: cervical(5), endome-
trial(4), uterine(1) and ovarian(1) cancer. Previous RT
dose prescription dose ranged from 45 to 59.4 Gy and 6
patients underwent to brachytherapy (range: 7-28 Gy).
Two patients, with marginal lymph node recurrence,
were irradiated with protons with up to a total dose of
25 GyRBE and 51 GyRBE respectively. The remaining
women underwent to CIRT with a median total dose of
50.4 GyRBE (range: 36-57) administered in a median
number of 12 fractions. Seven patients with PSWr
received surgical spacer placement by open surgery to
keep intestinal tracts apart from the tumor, as the distan-
ce between tumor and nearest intestinal tracts was not
sufficient. No pts received concurrent chemotherapy.
Preliminary local control (LC) and toxicity profile
according to CTCAE V4.03 scale were evaluated.

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Results: All patients completed the planned treat- computed tomography image-guidance. We registered
ment and no acute toxicities G>2 were observed. For toxicity according to Common Terminology Criteria for
the evaluable patients, 1 case of intermediate G≥3 toxi- Adverse Events (CTCAE) v4.0. Biochemical relapse
city was reported in women received sequential was defined as a PSA increase > 20% compared with
Bevacizumab (BV). For pts with a follow-up ≥ 3 the pre-EBRT re-treatment value. Survival curves were
months, median LC was 9 months (range: 6-14), calculated using the Kaplan-Meier method.
median metastasis-free-survival was 7 months (range: Results: All patients received a total dose of 50 Gy
3-21) and median overall survival was 9 months (25 x 2 Gy), and 7 (46.6%) had concomitant androgen
(range: 6-20). 1 pt experienced local progression and 4 deprivation therapy (median duration of 12 months).
pts died for systemic progression. Patient recruitment With a median follow-up of 40.9 months, the 2-year and
and data are still ongoing. 4-year biochemical relapse-free survival were 55% and
Conclusions: For pts with PSWr a PT approach 35%, respectively. Acute and late genito-urinary (GU)
seems to be feasible and our results showed a promising toxicity ≥ 2 were recorded in 4 (26.6%) and 5 (33.3%)
short-term outcome and limited radiation-related side patients, respectively, and the 4-year late GU toxicity
effects. It is still unclear how PT and BV interact. was 30%. Acute gastrointestinal toxicity ≥ 2 was recor-
Preliminary results are encouraging but a longer follow- ded in 2 (13.3%) cases, whereas no patient experienced
up and large patient accrual are required. late toxicity.
Conclusions: Despite the inherent bias of a retro-
spective analysis, our long-term results showed a low
toxicity profile with a relatively low rate of biochemical
control for HT re-treatment in patients affected by local
C013
radiorecurrent prostate cancer. Prospective trials are
needed to investigate the role of EBRT in this setting.
HELICAL TOMOTHERAPY RE-IRRADIATION FOR
PATIENTS AFFECTED BY LOCAL RADIORECUR-
RENT PROSTATE CANCER
C. Mariucci1, G. Ingrosso1, V. Bini2, S. Saldi3,
M. Lupattelli3, A. Frattegiani3, E. Perrucci3,
I. Palumbo1, L. Falcinelli3, G. Centofanti1,
R. Bellavita3, C. Aristei1
1Radiation Oncology Section, Department of Surgical

and Biomedical Science, University of Perugia;


2Internal Medicine, Endocrine and Metabolic Science

Section, University of Perugia; 3Radiation Oncology


Section, Perugia General Hospital, Italy
Aims: Salvage re-irradiation in patients affected by
radiorecurrent prostate cancer might be a valid as well
as challenging treatment option. The aim of this study
was to evaluate feasibility and toxicity of salvage exter-
nal beam radiotherapy (EBRT) re-treatment in patients
affected by radiorecurrent prostate cancer within the
prostate gland or the prostate bed.
Methods: 15 patients underwent EBRT re-treatment
using helical tomotherapy (HT), with daily Megavolt Figure 1.

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Oral Communications

Oral Communications

nal vesicles (n = 1), lung metastases (n = 2) and relapses


in prostate or prostatic bed (n = 5). The median PSA
CO001
68GA-PSMA PET-TC-GUIDED METASTASES prior to RT was 0.65 ng/mL (range 0.14 – 6.49 ng/mL),
the median PSA-doubling time was 5.9 months (range
0.61 – 140) and the median PSA post RT was 0.61
DIRECTED STEREOTACTIC BODY RADIOTHERAPY

ng/mL (range 0.02-30). A median dose of 35 Gy (range


IN PROSTATIC CANCER PATIENTS: A MONOISTI-

25–70 Gy) was delivered by VMAT-IGRT in 5–10 frac-


TUTIONAL PRELIMINARY EXPERIENCE
M. Rigo1, R. Mazzola1, V. Figlia1, L. Nicosia1,
N. Giaj-Levra1, F. Ricchetti1, G. Napoli1, R. Ruggieri1, tions (the median BED2Gy was 144 Gy). At a median
F. Alongi1,2 follow-up of 12.6 months (range 3–24 months), 16
1Advanced Radiation Oncology Department, IRCCS patients out of 34 patients irradiated (47%) were in
Sacro Cuore Don Calabria, Negrar (VR); 2Università di remission and 18 were in progression. In particular, 8
Brescia, Italy out of 12 castration resistant (CR) patients (67%) and 8
out of 22 castration sensitive (CS) patients (36%) were
Aims: To investigate the efficacy and toxicity of
in progression. The actuarial 1-year LC, PFS and CSS
68Ga-PSMA PET-CT-guided stereotactic radiotherapy
rates were 93, 47 and 100%. Systemic treatment free
(SBRT) in the treatment of oligometastatic prostate can-
cer. survival was 8 months (range 2-24 months). No one
Methods: A total of 34 prostate cancer patients with patient experienced grade ≥3 acute gastrointestinal or
biochemical relapse (22 castration sensitive and 12 urinary toxicity.
castration resistant) were treated with Volumetric Conclusions: By providing optimal LC, low toxi-
Modulated Arc Therapy and Image-Guided RT (VMAT- city and a promising PFS, 68Ga PSMA PET-CT-guided
IGRT) on ≤5 metastastatic sites detected by 68Ga metastases directed SBRT may be considered a promi-
PSMA PET-CT. Androgen deprivation therapy was sing treatment strategy in patients with oligometastatic
continued in castration resistant (CR) patients. prostate cancer, allowing to postpone systemic thera-
Results: A total of 74 metastases in 34 patients were pies. Further studies could confirm this promising fin-
treated with SBRT. The involved sites were pelvic dings.
lymph or paraaortic nodes (n = 53), bone (n = 13), semi-

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

months in patients with <0.25, 0.25-0.49, 0.5-0.74,


0.75-0.99, 1-1.49, >1.5 ng/ml, respectively, p 0,013).
CO002

Conclusions: Based on the present experience, high


PSA level at relapse, site of metastatic disease and base-
EVALUATION OF PROGNOSTIC FACTORS IN PRO-

line high risk-class should not be considered as negative


STATE CANCER PATIENTS WITH POST PROSTA-

prognostic factors in order to guide therapeutic approa-


TECTOMY BIOCHEMICAL RELAPSE AND RE-STA-

ch in this setting. Literature data show that metastasis


GED WITH CHOLINE PET/CT: A MULTICENTRIC

directed therapy could improve outcome in particular


RETROSPECTIVE SERIES
M. Aquilano1, M. lo Russo1, T. Carfagno2, S. Croci2,
R. Santini3, M. Stefanacci3, S. Fondelli4, R. Barca4, subset of patients, and none of the available treatment
P. Alpi4, G. Ingrosso5, M. Bottero6, E. Alì6, approaches (e.g SBRT) should be avoided based on
S. Borghesi7 , G. Caramia1, G. Francolini1, B. Detti1, abovementioned factors. Currently, treatment should be
L. Livi1 tailored on the basis of burden of disease detected at re-
1Dipartimento di Radioterapia Oncologica Azienda
staging.
Ospedaliera Universitaria Careggi, Firenze; 2Unità di
Radioterapia Oncologica, Ospedale Universitario di
Siena; 3Dipartimento di Radioterapia Oncologica,
Ospedale San Jacopo Pistoia; 4Dipartimento di
CO003

Radioterapia Oncologica, Azienda USL Toscana-


DETECTION RATE, PATTERN OF RELAPSE AND
Centro, Ospedale S. Maria Annunziata, Florence; INFLUENCE ON THERAPEUTIC DECISION OF
5Dipartimento di Scienze Chirurgiche e Biomediche, PSMA PET/CT IN PATIENTS AFFECTED BY BIO-
Università di Perugia and Ospedale Santa Maria della CHEMICAL RECURRENCE AFTER RADICAL PRO-
Misericordia, Perugia; 6Dipartimento Diagnostica per
Immagini, Imaging Molecolare, Radiologia
STATECTOMY, A RETROSPECTIVE CASE-SERIES
L. Dominici, G. Ingrosso, A. Bruni, S. Borghesi,
Interventistica e Radioterapia Policlinico Tor Vergata, M. Bottero, A. Lancia, A.R. Filippi, R. Santoni,
Roma; 7Dipartimento di Radioterapia Oncologica, C. Aristei, E. Mazzeo, L. Frassinelli, G. Francolini,
Ospedale San Donato Arezzo, Italy B. Detti, L. Livi
Aims: To describe outcomes after choline PET/CT Department of Radiation Oncology, University of
re-staging in a multi-institutional cohort of prostate can- Florence, Azienda Ospedaliero-Universitaria Careggi,
cer (pCa) patients with locoregional or distant recurren- Florence; Department of Surgical and Biomedical
ce after primary surgery. Science, University of Perugia and Santa Maria della
Methods: Data of 410 PCa patients treated in four Misericordia Hospital, Perugia; Radiation Oncology
Italian Centers were retrospectively reviewed. All Department, AOU Policlinico di Modena; Unit of
patients underwent re-staging with choline PET/CT for Radiation Oncology, S.Donato Hospital, Arezzo;
post-prostatectomy biochemical recurrence. Patients Department of Diagnostic Imaging, Molecular Imaging,
were defined as oligometastatic (OM) if PSMA Interventional Radiology and Radiotherapy, Tor Vergata
PET/CT detected <3 non-visceral lesions (either bone General Hospital, Rome; Department of Medical
or nodal), according to Italian Association of Sciences and Infectious Diseases, Unit of Radiation
Radiotherapy and Clinical Oncology (AIRO) defini- Therapy, IRCCS Fondazione Policlinico San Matteo,
tion. Pattern of treatment after re-staging and survival Pavia; Radiation Oncology Department, Fondazione
outcomes were analyzed. Association between risk Policlinico Tor Vergata, Rome; Radiation Oncology
class (low/intermediate vs high), site of metastatic Section, Department of Surgical and Biomedical
Science, University of Perugia and Perugia General
disease (bone vs nodal) and PSA subgroup levels at bio-
Hospital; Radiotherapy Unit - Department of Oncology
chemical relapse (<0.25, 0.25-0.49, 0.5-0.74, 0.75-0.99,
and Hematology, University Hospital of Modena, Italy
1-1.49, >1.5) with overall survival was explored perfor-
ming Kaplan meyer analysis. Aims: (68Ga) Prostate-specific membrane antigen
Results: At diagnosis, median age was 65.5 years (PSMA) PET/CT is widely used in patients with bio-
(45-88) and median PSA level was 20.9 ng/mL (4-320), chemical recurrence (BCR) after radical
majority of patients (78,5%) was affected by high risk prostatectomy.1 Furthermore, standard restaging ima-
disease. Median time to biochemical relapse after pri- ging has been proven to be significantly less sensitive
mary treatment was 51 months (1-1381) and median than PSMA PET/CT.2 According to National
PSA level at relapse was 3,5 ng/mL (0,1-134). Choline Comprehensive Cancer Network (NCCN)3 use of
PET/CT had a crude detection rate of 68.5%, with 96% PSMA should be limited to clinical trials or registry,
of positive exams detecting OM disease. 17.8, 44.1 and however, due to its high detection rate, application in
6.3% of patients were treated with SBRT, exclusive clinical practice is increasing4,5 PSMA PET/CT showed
androgen deprivation therapy (ADT) and chemothe- to impact clinical decision in the scenario of early
rapy+ADT, respectively. Median overall survival was BCR.6
7.4 years (0-24). Only PSA at biochemical relapse Methods: Data about PSMA PET/CT after BCR in
showed significant impact on survival. Surprisingly, four different institutes were collected. All patients
patients with PSA at relapse had a longer median survi- underwent radical surgery and developed BCR (defined
val if compared to others (102, 71, 84, 79, 102, 110 as PSA rise above 0.2 ng/ml7), with a PSA <1 ng/ml.

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Oral Communications

Patients were defined as oligometastatic (OM) if PSMA


PET/CT detected <3 non-visceral lesions (either bone
CO004

or nodal), according to Italian Association of


Radiotherapy and Clinical Oncology (AIRO) defini-
RESULTS AT LONG-TERM AFTER RADIOSURGERY

tion.8 Treatment after PSMA PET/CT scan were also


OF VESTIBULAR SCHWANNOMAS. A MULTICEN-

reported. Gleason score <7or>7, Low/intermediate or


TRE RETROSPECTIVE ANALYSIS
P. Anselmo1, V. Pinzi2, S. Terenzi1, E. De Martin2,
High risk baseline classification, PSA at recurrence F. Trippa1, P. Gaviani3, M. Casale1, L. Fariselli2,
<or>0.5 ng/ml, PSA DT <or>10 months and time to E. Maranzano1
recurrence (TTR) <or> than median of the analysed 1Radiotherapy Oncology Centre, S. Maria Hospital,
cohort (29.5 months), were considered as binomial Terni; 2Dept. of Neurosurgery, Radiotherapy Unit,
variables and Chi-squared test was performed in order Fondazione IRCCS Istituto neurologico Carlo Besta,
to evaluate the impact of these factors on PSMA Milan; 3Clinic Neuro-Oncology Unit, Fondazione
PET/CT detection rate and the probability to detect OM IRCCS Istituto neurologico Carlo Besta, Milan, Italy
disease. Chi-squared test was used to explore the asso-
ciation between the administration of RT with ablative Purpose: This retrospective report regards patients
instead of palliative-only intent and the probability to with sporadic vestibular schwannomas (VS) treated
undergo ADT during the clinical history. with a single dose of SRS with a minimum follow-up >
Results: 92 patients from 4 institutes were inclu- 3 years. The aim of the study was to analyse tumor con-
ded. PSMA PET CT detection rate was 56.5% (52/92) trol and toxicity associated to SRS.
and OM disease was detected in 92.3% of patients. Methods: Patients included received Linac-based
After positive scan 13.5% of patients still lies on obser- (LB) SRS or Cyber-Knife (CK) SRS. Patients not able
vation, ADT alone was administered in 30.8% of cases, to discriminate words or not hearing at all, were scored
Stereotactic body RT (SBRT) alone was delivered to as ‘non-serviceable hearing’. Trigeminal and facial
44.2% of patients and 11.5% of patients underwent con- nerve functions were assessed before and after treat-
comitant SBRT and ADT, as summarized in Table 1. ment.
Chi-squared test showed a higher rate of positive PSMA Results: Between 2002 and 2016, 153 VS were
PET/CT for patients with Gleason score >7 (p=0.004) treated in 153 patients. 116 (76%) VS received LB-SRS
and TTR shorter than 29.5 months (p=0.003). SBRT and 37 (24%) CK-SRS. Male/female ratio was 70/83.
significantly reduced the risk of systemic ADT Median age was 60y (range, 20-84). Median prescribed
(p=0.03). dose was 14Gy (range, 12-20). Median tumor diameter
Discussion: PSMA PET/CT showed a high detec- was 5 mm (range, 0.2-23). SRS was performed as sal-
vage therapy for recurrent or progressive tumors in 36
tion rate. OM disease was detected in most cases, avoi-
(23%) patients already submitted to total or subtotal
ding unnecessary prostate bed RT, and PSMA PET/CT
resection (10-28% and 26-72%, respectively). The
guided SBRT seems to have significant impact on this
other 117 (77%) patients underwent SRS alone. 25
specific setting.
(16%), 61 (40%), 52 (34%) and 15 (10%) VS were clas-
sified as Koos tumor grade I, II, III and IV, respectively.
Table 1. 147 (96%) patients had hearing loss as an initial symp-
tom, of which 73 (48%) with “non-serviceable” hearing
function. Trigeminal neuralgia and facial pain/parae-
sthesia were presenting symptoms in 9 (6%) and 27
(17%) patients, respectively. At a median follow-up of
6 years (range, 3–16), 32 patients (21%) had an objec-
tive improvement of their initial symptoms, 94 (61%)
stable symptoms, and 27 (18%) worsened their pre-
treatment symptoms. Only in 1 case MRI showed pro-
gression of VS. Among patients with “serviceable-hea-
ring” (80-52%), 54 (67%) maintained their functional
hearing score, 11 (14%) improved and 19 (19%) worse-
ned. 5 of 126 (4%) patients without pre-SRS facial toxi-
city, developed incomplete facial nerve palsy, that
regressed in a median time of 6 months. 15 of 144
(10%) patients without pre-SRS trigeminal neuralgia
developed trigeminal toxicity which was transient or
stable/mild during follow-up in 13 (9%) patients. In
only 2 cases (1%) trigeminal toxicity was severe and
appeared at a median time of 12 months. Crude radio-
logic tumor control rate was 98%.
Conclusions: SRS in VS allowed an excellent tumor
control and hearing preservation rate. Neurological
toxicity resulted acceptable and similar to that reported

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

in literature. Prospective studies are needed to draw Conclusions: The addition of delayed contrast
definitive conclusions. extravasation MRI information in the identification of
the radiosurgery treatment target can affect the planning
optimisation process in the re-irradiation scenario of
relapsing gliobastoma multiforme. Further investiga-
tions on the actual clinical impact of this imaging
CO005
INTRODUCING CONTRAST-DELAYED MAGNETIC modality seems appropriate.
RESONANCE IMAGING IN RADIOSURGERY
TREATMENT OF GLIOBLASTOMA.
V. Pinzi1, E. De Martin2, F. Padelli2 , Y. Mardor3,
CO006

D. Last3, V. Cuccarini4, L. Fariselli1, D. Aquino4 NON-COPLANAR MONO-ISOCENTER STEREOTAC-


1Fondazione IRCCS Istituto Neurologico Carlo Besta,
TIC RADIOTHERAPY (HYPERAR TM) FOR THE
Radiotherapy Unit, Milan, Italy; 2Fondazione IRCCS
SIMULTANEOUS TREATMENT OF MULTIPLE
Istituto Neurologico Carlo Besta, Health Department,
BRAIN METASTASES FROM SOLID TUMORS:
Milan, Italy; 3Sheba Medical Center, Advanced UPDATED RESULTS FROM THE FIRST
Technology Center, Tel Hashomer, Israel; 4Fondazione WORLDWIDE EXPERIENCE
IRCCS Istituto Neurologico Carlo Besta, L. Nicosia1, V. Figlia1, N. Giaj-Levra1, R. Mazzola1,
Neuroradiology Unit, Milan, Italy F. Ricchetti1, M. Rigo1, R. Ruggieri1, F. Alongi1
1Radiation Oncology, IRCCS Sacro Cuore Don
Aims: Stereotactic radiosurgery (SRS) of intracra-
nial lesions is based on the accurate delivery of very Calabria Hospital, Negrar-Verona, Italy
high doses of radiation. Milestone of this technique is Introduction: Radiosurgery (SRS) or stereotactic
therefore the acquisition of appropriate imaging for a fractionated radiotherapy (SFRT) is an effective treat-
really optimized treatment planning. Conventional ment option in the management of multiple brain meta-
magnetic resonance imaging (MRI) may not be able to stases (BMs). We reported the updated results of the
differentiate tumor to non-tumor enhancing tissues. In first world-wide experience using a dedicated mono-
this study we introduced treatment response assessment isocenter non-coplanar LINAC-based technique
maps (TRAMs), based on the concept of delayed con- (HyperArc™ Varian Medical System) in the treatment
trast extravasation MRI, into a radiosurgery treatment of multiple BMs.
planning system (TPS) for target identification purpo- Materials and Methods: patients with BMs (maxi-
ses. mum diameter 30 mm), life expectancy >3 months and
Methods: Five patients presenting with disease pro- good performance status were treated with HyperArc™
gression of gliobastoma multiforme (GBM), previously and retrospectively evaluated. Local progression-free
treated according to our clinical practice, were enrolled survival (LPFS), intracranial progression-free survival
in this study. For all patients an irradiation target volu- (iPFS), overall survival (OS) and intracranial overall
me was defined by contouring the enhancement area on survival (iOS) were evaluated. Predictive and progno-
a 3D T1-weighted MRI sequence (1-mm slice thick- stic factors were assessed.
ness, contiguous slices) acquired after contrast agent Results: 102 patients accounting for 677 BMs with
intravenous injection. TRAMs were obtained subtrac- a median follow-up of 12 months were treated. Median
ting the post-contrast 3D T1-weighted images from the treated metastases number was 7 (1-21). Primary tumor
same MRI sequences acquired about 75 minutes after. histology was NSCLC (42.1%), breast (30.3%), mela-
Tumor burden was then also identified and outlined on noma (13.7%), others (13.9%). Six and 12-month LPFS
TRAMs images, specifically processed to be imported were 93.2% and 82.5%, respectively. At the univariate
in the TPS. Maintaining the target coverage maximiza- analysis NSCLC and breast histology correlated with a
tion as primary objective (prescription dose to 95% of better LPFS (p=0.00001). Median time to iPFS was 5
the target) for comparison purposes, plan optimization months (range 3-10) irrespective from histology
tests were performed in two ways for each patient: con- (p=0.97). Fourteen patients received 19 further courses
sidering only the conventionally delineated target or of HyperArc™ (range 2-5) in case of intracranial oligo-
considering only the TRAMs delineated target. The progression. The 6- and 12 months iOS were 85.1% and
plans obtained for each patient were compared in terms 65.5% respectively, regardless of BM number (≤ 5 ver-
of target volume and dose volume histogram (DVH) sus 6-9 versus ≥10; p=0.48). WBRT was administered
data. to 10 patients after median 5 months (range 5-14), and
Results:  For all patients the target volume contou- 4 out of them received WBRT after a second
red on the TRAMs images was smaller than the one HyperArc™ course. No acute adverse event higher than
contoured on conventional MRI, with a fraction of grade 2 occurred; 1 (0.14%) patient had histologically
approximately ½ in one case. Non-overlapping areas confirmed radionecrosis occurred 12 months after SRS.
were also identified. Consequently, the percentage of Conclusions: HyperArc™ is a safe and effective
healthy brain volume receiving 12 Gy was always in technique for multiple BM treatment also in case of
favour of the TRAM target case, with a reduction from multiple courses. The reduced overall treatment time
1.5 to 5%. Doses to other OARs adjacent to the target and the possibility to spare safely normal brain give the
were also reduced. possibility to deliver multiple SRS/SFRT courses and in

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Oral Communications

selected cases to delay the administration of WBRT. A treatment planning CT images can distinguish patients
future prospective study is needed to evaluate the long- with low and high risk of tumor progression and disease
term effectiveness of multiple BM SRS/SFRT. specific death in early stage lung cancer treated with
SBRT.

CO007
Table 1. Performance results of the linear discriminant analysis classifier.
A RADIOMIC APPROACH TO PREDICT NODAL
AND DISTANT RELAPSE IN A COHORT OF
PATIENTS TREATED WITH STEREOTACTIC BODY Training Validation

Specificity 0.84±0.14 0.83±0.24


RADIATION THERAPY FOR EARLY STAGE NON
Sensitivity 0.89±0.01 0.87±0.01
SMALL CELL LUNG CANCER
D. Franceschini, L. Cozzi, D. Pezzulla, F. De Rose, Accuracy 0.87±0.07 0.85±0.12
C. Franzese, S. Tomatis, G. Reggiori, M. Scorsetti AUC 0.84±0.04 0.73±0.05
Radiotherapy and Radiosurgery Department,
Humanitas Clinical and Research Center, Taranto, Italy
Aims: Regional and distant relapse remain a signi-
ficant issue in the treatment of early stage non small cell
lung cancer with Stereotactic Body Radiation Therapy
(SBRT). In this work we present a radiomic approach
using features extracted by routine planning CT, to pre-
dict the risk of nodal and distant recurrence.
Methods: A cohort of 102 patients was retrospecti-
vely investigated. All patients were affected by early
stage (T1-T2) lung cancer and received the same radia-
tion treatment with 48Gy delivered in 4 fractions. For
all patients, a set of 45 radiomics textural features was
computed for the tumor volumes segmented on the
treatment planning CT images. Patients were split into
two independent cohorts used for training (70% of
cases) and validation (30% of cases). A stepwise
backward linear discriminant analysis (LDA) was Figure 1. Actuarial curves for PFS and DS OS over the entire training and test
applied as a classifier to identify patients at risk of
cohorts (in both cases the difference was not significant) and the same data strat-
lymph-nodal progression. The performance of the ified in low and high risk groups identified.
model was assessed by means of standard metrics deri-
ved from the confusion matrix. Furthermore, all textural
features were correlated to survival data to build predic-
tive models: the features/predictors found significant at
CO008

univariate analysis and to elastic net regularization, A PRACTICAL DOCUMENT ON IMRT IN


were included in a multivariate model to predict disease
specific progression free survival (PFS) and disease
MEDIASTINAL LYMPHOMAS
S. Meregalli1, A. Di Russo2, G. Simontacchi3,
specific survival (DS OS). Low and high risk groups A. Alghisi4, M. Buglione4, P. Ciammella5, G. De
were identified by maximizing the separation by means Marco6, V. De Sanctis7, B. Lanfranchi6, M. Levis8,
of the Youden method. S. Vagge9, U. Ricardi8, A.R. Filippi10, Commissione
Results: In the total cohort (77 (75.5%) males and Radioterapia FIL
25 (24.5%) females, median age 76.6 years), 15 patients 1S.C. Radioterapia ASST Monza, Ospedale San
presented nodal progression at the time of analysis (11 Gerardo; 2Fondazione IRCCS - Istituto Nazionale dei
in the training and 4 in the validation sets); 19 patients Tumori Milano; 3S.C. Radioterapia Azienda
(18.6%) died because of disease specific causes, 25 Ospedaliero Universitaria Careggi-Firenze;
(24.5%) died for other reasons, 28 (27.5%) were alive 4Radioterapia Oncologica, Università e Spedali Civili -
without disease and 30 (29.4%) with either local or Brescia; 5S.C. Radioterapia Oncologica USL-IRCCS
distant progression. The mean tumor volume was Reggio Emilia; 6S.C. Radioterapia, Azienda
5.6±6.4cm3. Table 1 summarizes the performance Ospedaliera-Universitaria di Modena; 7S.C.
results of the LDA classifier. Figure 1 illustrates the Radioterapia Oncologica, Azienda Ospedaliera
actuarial curves for PFS and DS OS over the entire trai- Università S. Andrea, Sapienza Università di Roma;
ning and test cohorts (in both cases the difference was 8S.C. Radioterapia Oncologica- Dipartimento di
not significant) and the same data stratified in low and Oncologia, Università di Torino; 9S. C. Radioterapia,
high risk groups identified. In all case highly significant Azienda Ospedaliera Universitaria San Martino di
differences were identified. Genova; 10Fondazione IRCCS Policlinico San Matteo
Conclusions: Radiomics features extracted from

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Aims: Advances in therapy have resulted in impro-


ved cure rates and an increasing number of long-term
CO009

lymphoma survivors. However, radiotherapy (RT)-rela-


ted late effects are still a significant issue, particularly
ONCE-DAILY PARTIAL BREAST IRRADIATION

for young patients with mediastinal disease (heart,


(OD-PBI): PRELIMINARY LONG TERM RESULTS

second cancers). In many Centres worldwide, RT tech-


WITH HELICAL TOMOTHERAPY HI-ART
U. De Paula, C. Ghini, A.D. Andrulli, G. Apicella,
nological evolution substantially changed radiation R. Barbara, C. Caruso, S. Gomellini, E. Ponti,
dose planning and delivery. This consensus document A. Caccavari, L. Costarelli, M. La Pinta, M. Mauri,
aimed to analyze and summarize the current knowledge P. Scavina, A. Petrocchi, R. Rossi, L. Broglia,
on IMRT and IGRT for mediastinal lymphoma, provi- A. Loreti, L. Fortunato
ding the basis for standardization among FIL studies. UOC Radioterapia, A.O.C.O. San Giovanni Addolorata,
Methods: A working group was set up within the Roma, Italy
FIL (Fondazione Italiana Linfomi) in May 2018. After
a first meeting, the group adopted a dedicated platform Aims: Accelerated partial breast irradiation (APBI)
to share articles and material. Two group coordinators has become a valid treatment in the field of breast con-
redacted a first document draft, that was further discus- servative therapy for pts with early-stage breast cancer.
sed and finalized in a subsequent meeting. Topics of The current schedule (38,5 Gy in 10 fraction b.i.d. over
interest were: 1) IMRT techniques; 2) specific dose 5 days) is often associated with good local control at the
constraints for the following OAR: heart, lungs, thy- expense of greater toxicity and worse cosmetic results
roid, breasts; 3) IGRT protocols. respect to standard fractionation. We report long-term
Results: According to the planned schedule, the results in 162 pts treated with once-daily PBI (OD-
final document has been presented at FIL National mee- PBI). We analyzed local recurrence (LR), regional
ting in November 2018. Data review clearly showed recurrence (RR), axillary failure (AF), toxicity and
that IMRT, mainly if combined with IGRT, may allow cosmesis. Secondary end-point were: disease free survi-
for shrinkage of irradiated volumes and therefore an val (DFS), distant-disease-free-survival (DDFS), cause-
essential reduction of high dose to OAR. IMRT emer- specific-survival (CSS) and overall-survival (OS).
ged as superior to conformal RT for heart sparing and
for reducing the dose to the thyroid gland. Low dose
spread to the lungs and breast can be limited by using Table 1.
specific dose constraints. Suggested constraints for
low/intermediate dose to optimize planning for all
organs at risk have been created and approved by the
whole group (Table 1). The use and frequency of IGRT
resulted widely variable among Centres, as the use of
breath control techniques, and the group advised for
routine use without specifications. An individual
approach considering the different age, gender, and
finality of RT has been strongly recommended.
Conclusions: As lymphoma therapy continues to
evolve, with an emphasis on treatment reduction, radia-
tion oncologists should use at best the available tools to
minimize the dose to organs at risk. This consensus
document provides for the first time indications on the
use of IMRT/IGRT techniques for mediastinal lympho-
mas. It will be rapidly adopted by FIL for future trials
and might be useful for clinical practice.

Table 1.

Methods: From December 2010 to December 2018,


347 pts with invasive breast cancer (mean age:65,2 yrs;
range 50-86) underwent OD-PBI (38,5 Gy delivered in
10 daily fractions) delivered by Helical-Tomotherapy.
We present results on 162 pts with a minimum follow-
up of 55 months (Table 1). Eligibility criteria included
unifocal disease up to 3 cm with R0 (at least 2 mm of
clear margins) without extensive (<25%) intraductal
disease or LVSI. Pts with pN1a involvment without

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Oral Communications

extracapsular invasion were included. All genetic compared between node-negative (N-) and (N+)
subtypes (Stanford's classification) were admitted. cohorts. Local recurrence (LR), regional recurrence
Patients and physicians assessed cosmesis during FU (RR), axillary failure (AF), distant metastases (DM),
according to EORTC Cosmetic Rating System. disease-free survival (DFS), cause-specific survival
Results: With a median FU of 72.3 months (range: (CSS), and overall survival (OS) were analyzed.
53-101) no LR, RR and AF were reported. All pts com- Results: N+ pts were slightly younger (mean age:
pleted the treatment without any interruption; 17 pts 63,7 yrs vs 64,9 yrs; p=0,37), had larger tumors (DM:
(10%) experienced a grade 1 and 2 pts (1,2%) grade 2 14,1 mm vs 10,6 mm; p= 0,04), and not were more
acute skin toxicity. In 4 pts a grade 1 (2,4%) late skin likely to receive chemotherapy. Sixteen (89%) had a
toxicity and in 9 pts (5,5%) subcutaneous fibrosis pure IDC histological type while 11% were ILC (p=
according to CTCAE v4.0, was observed. The patients 0,01). Eleven pts (61%) had a Luminal A-like genetic
assessed percentage of (respectively) “excellent” and sub-type, 5(28%) were Luminal B-Like and 2(11%)
“good” cosmetic results were 66% and 32% at baseline; were HER 2+ non Luminal. Only 3 pts (17%) had a
75% and 22% at 1 year; 77% and 19% at 2 yrs. The degree of differentiation G1, while 83% had a degree of
same assessment given by the physicians occurred in differentiation G2/G3 (p=0,008). Median FU was 73,4
70% and 27% (baseline); 87% and 12%, (1 year) and in mths for N+ pts and 69 mths for N- pts (p=0,47). No
82% and 15% (2 yrs). A very low rate of pts and physi- differences were seen in 5-year actuarial rates of LR
cians (1% and 4%, respectively) judged as “fair” or (0% vs. 0%), AF (0% vs. 0%), RR (0% vs 0%), DM
“poor” the cosmetic outcome at any time. One pt deve- (0% vs 0%),CSS (100% vs 100%), or OS (88% vs.
loped a contralateral breast tumor 12 months after the 97.2%, p=0,47) between the two groups. One pt N-
end of the OD-PBI. There were no cases of distant developed a contralateral breast tumor 12 months after
metastases. OS rate at 3 and 5 yrs were 98.8 % and the end of the OD-PBI. Since no recurrence event was
96.3%, respectively. detected, age, tumor size, receptor status, chemothe-
Conclusions: OD-PBI with Helical Tomotherapy rapy, histological type and N- stage were not associated
HI-ART yielded good cosmetic results without compro- with LR, RR and AF.
mising local control efficacy in pts who have undergone Conclusions: No differences were seen in the rates
conservative surgery. of LR, RR or AF between N- and N+ pts after OD-PBI.
These results support the continued enrollment of N+
pts in Phase III trials evaluating the efficacy of APBI
including the National Surgical Adjuvant Breast and
CO010
Bowel Project-B39/Radiation Therapy Oncology
Group 0413.
PROGNOSTIC VALUE OF LYMPH-NODE STATUS
AFTER ONCE-DAILY PARTIAL BREAST IRRADIA-
TION (OD-PBI) WITH HELICAL-TOMOTHERAPY
HI-ART: PRELIMINARY RESULTS
C. Ghini, A.D. Andrulli, G. Apicella, R. Barbara,
CO011

C. Caruso, S. Gomellini, E. Ponti, L. Costarelli,


INSPIRATION LUNG VOLUME AS PREDICTOR OF
A. Caccavari, M. Mauri, P. Scavina, R. Rossi, DOSIMETRIC BENEFIT IN BREAST CANCER
L. Broglia, L. Fortunato, M. La Pinta, P.D. Trifan, PATIENTS TREATED WITH DEEP INSPIRATION
U. De Paula BREATH HOLD
U.O.C. Radioterapia Policlinico Umberto I, S. Palizzi, E. Ippolito, S. Silipigni, C. Di Venanzio,
U.O.C.Radioterapia, A.O.C.O. San Giovanni- V. Lolli, A. Di Donato, G.M. Petrianni, B. Santo,
Addolorata, Italy S. Gentile, I. Ridolfi, A. Carnevale, M. Fiore,
L. Trodella, R.M. D’Angelillo, S. Ramella
Aims: According to the update of the Consensus
Policlinico Universitario Campus Biomedico, Roma,
Statement of the ASTRO of January 2015, the involve- Italy
ment of the axillary lymph nodes pN1a (one to three
nodal metastases) is not yet considered eligibility crite- Aims: Deep inspiration breath hold radiotherapy
ria for pts applying to APBI. Recently, several studies (DIBH RT) has been demonstrated to reduce heart
have shown, instead, has no prognostic significance on doses in patients with left side breast cancer. However,
the incidence of loco-regional recurrences. The purpose its routine use requires patients’ compliance and increa-
of this analysis is compare outcomes after once-day ses staff workload and treatment time. The aim of this
partial breast irradiation (OD-PBI) between N- and N+ study was to identify treatment planning characteristics
pts. that correlate with heart sparing and therefore guide
Methods: From December 2010 to December 2018, patients selection.
347 pts with invasive breast cancer (mean age:65,2 yrs; Methods: We retrospectively reviewed treatment
range 50-86) underwent OD-PBI (38,5 Gy/10 daily plans of 210 patients with left-sided breast cancer trea-
fractions) delivered by Helical-Tomotherapy. We pre- ted with breast adjuvant radiotherapy at our institution.
sent results on 162 pts with a minimum follow-up of 55 All patients had both free-breathing (FB) and DIBH
months including 18 node-positive (N+) cases. Of these treatment plans. Mean and maximum heart dose (mHD,
13 pts (72%) were pN1a and 5 (28%) pts were pN1mi. MHD), maximum dose to LAD (LAD Dmax), were
Clinical, pathologic, and treatment-related factors were recorded form both plans and the differences were cal-

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

culated (∆, delta values). Pearson correlations of ∆ patients (pts) with PM or ICD undergone RT and our
values with patient related parameters (PTVcc, inspira- results in terms of CIED malfunctioning.
tion lung volume, distance from the heart wall to the Methods: 34 consecutive CIED pts admitted to our
tangent field during free breathing and DIBH, breast Institution were evaluated. Pts were stratified into three
separation) were carried out. Furthermore, receiver- classes. The first group included pts with PM and spon-
operating characteristic (ROC) analysis was performed taneous activity; the second one, pts with PM but
to select the threshold of values of patients related para- without any residual spontaneous activity; the third
meters that may predict the benefit for heart dosimetry group included pts with ICD. For the first two groups,
of DIBH over free-breathing. the cardiologist of reference evaluated pts before and
Results: Four hundred twenty plans were evaluated. after every RT fraction, setting PM in asynchronous
DIBH plans decreased mHD, MHD and LAD Dmax by mode during RT delivery. In the third group, the cardio-
21%, 66% and 47% respectively (see table 1). Delta logist disabled and enabled ICD before and after every
MHD correlated positively with lung inspiration volu- RT section, monitoring cardiac activity during the treat-
me (p=<0.05). A negative correlation was found ment delivery. Pts were classified in high risk and low
between Delta LAD Dmax and breast separation and risk when CIED distance from target was ≤10 cm and >
PTVcc (p=0.07). Inspiratory lung volume > 2163 cc 10 cm, respectively. CIED functioning was evaluated
achieved the 50% benefit of delta MHD (p=0.008, during and at the end of RT course.
AUC= 0.650). Results: 8/34 pts were treated with tomotherapy.
Conclusions: Most patients have significant dosi- Total dose ranged from 8 Gy to 78 Gy. 23/34 pts had
metric benefit with DIBH. Inspiratory lung volume > PM, 11/34 ICD. In 17 cases CIED distance from the tar-
2163 cc may be used for selection of patients who bene- get was ≤10 cm and in 17/34 distance was >10 cm. 8/17
fit the most of DIBH technique. and 2/17 low risk pts belonged to the first and the
second group, respectively. Among these pts (both
dependent and independent), 7 were treated with 6 MV
photons, the remaining 3 pts were treated with > 6 MV.
7/17 low-risk pts were ICD wearers: 5 were treated with
Table 1. Comparison of dose metrics between free-breathing (FB) and breath hold

6 MV photons, 2 with > 6 MV photons. 13/17 high-risk


(BH) plans.

pts had PM (dependent or independent), among these,


11 were treated with 6 MV photon and 2 pts with > 6
FB plans BH plans p

Heart mean dose (Gy) 1,38 1,14 <0.001


MV. 4/17 high-risk pts were ICD carriers: 3 pts were
DS=0,77 DS= 0,57 treated with 6M photons while 1 pt with > 6 MV.
Heart maximum dose (Gy) 32,5 19,6 <0.001 During or at the end of RT course, 24/34 pts showed not
DS= 12.7 DS= 12.3 CIED malfunctioning, 3/34 had atrial fibrillation and
LAD maximum dose (Gy) 12,54029 8,52751 <0.001 7/34 cases had ventricular events with no major clinical
DS=5,9 DS=3,9 effects. After a mean follow-up of 19 months (range 2-
Lung V20 Gy (%) 7,100156 7,5739512 <0.001 41), 12 pts were evaluable for late assessment of CIED
DS= 4,7 DS=4,0 functioning and no ventricular event was observed.
Conclusions: The introduction of a protocol for the
LAD: left descending artery; V20 Gy= lung volume receiving 20 Gy. management of pts with CIED allows a standardization
of the cardiological evaluation in RT workflow. In our
experience, RT seems to be safe for CIED wearers. A
larger number of pts will be required to confirm these
preliminary results.
CO012
MANAGEMENT OF PATIENTS WITH CARDIAC
PACEMAKERS (PM) OR IMPLANTABLE CARDIO-
CO013
VERTER-DEFIBRILLATOR (ICD) IN RADIOTHE-
RAPY WORKFLOW. DEVELOPMENT OF A PROTO- PHASE 2 TRIAL EVALUATING STEREOTACTIC
COL AND SAFETY REPORTS
S. Di Biase1, F. Fenu1, S. Costantini1, F. Cucciarelli1,
BODY RADIOTHERAPY (SBRT) AFTER INDUCTION

M. Di Benedetto1, L. Fabbietti1, M. Madia1,


CHEMOTHERAPY FOR PATIENTS WITH LOCALLY

A. Maucieri1, M. Montisci1, G. Travaglini1,


ADVANCED UNRESECTABLE PANCREATIC

M. Valenti 2, L. Vicenzi1, G. Mantello1


CANCER (LAPC02; NCT03158779): FEASIBILITY

1SOD Radioterapia, AOU Ospedali Riuniti di Ancona;


AND SAFETY PRELIMINARY RESULTS OF EUS-

2SOD Fisica Sanitaria, AOU Ospedali Riuniti di


GUIDED PLACEMENT OF NEW GOLDEN FIDUCIAL

Ancona, Italy
MARKERS
T. Comito, S. Carrara, C. Franzese, A. Tozzi, I. Renna,
Aims: Radiotherapy (RT) can influence cardiac L. Di Brina, C. Iftode, F. De Rose, P. Navarria,
implantable electronic devices (CIED) functioning. G.R. D'Agostino, D. Franceschini, P. Mancosu,
Consensus document from AIAC, AIRO and AIFM has G. Reggiori, S. Bozzarelli, S. Tomatis, A. Santoro,
been recently published but data on this issue are still A. Zerbi, M. Scorsetti
limited. We report our protocol for the management of Istituto Clinico Humanitas, Rozzano, Italy

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Oral Communications

Background and Aim: Radiation therapy plays an tamol. The procedures were performed in an outpatient
emerging role in the multi-modality treatment of locally setting.
advanced pancreatic cancer (LAPC). Stereotactic body Conclusions: This preliminary evaluation demon-
radiation therapy (SBRT) is an innovative radiation strated the feasibility and safety of the EUS-guided
technique, characterized by high prescription dose deli- fiducial placement using the new dedicated preloaded
vered in few fractions with a short overall treatment needle. Only minor technical difficulties due to the
time and increased local control rate. Endoscopic ultra- stiffness of the tumor did not affect the correct place-
sound (EUS)-guided fiducials placement allows to ment of the fiducials. Imaging at the time of simulation
accurately evaluate the target motion during SBRT deli- also revealed the migration rate to be extremely low.
very. The aim of our study is to report the technical fea-
sibility, safety and migration rate of fiducial marker pla-
cement in patients with LAPC enrolled in a phase II
CO014
study of SBRT after induction chemotherapy (LAPC02)
who underwent EUS-guided fiducial marker placement
SURGICAL MARGINS STATUS AND POSTOPERA-

for IGRT
TIVE COMPLICATIONS AFTER SBRT AS

Material and Methods: Patients with histologically


NEOADJUVANT APPROACH FOR PANCREATIC

proven unresectable LAPC, treated with induction che-


CANCER
N. Simoni1, I. Renna1, R. Micera1, G. Rossi1,
motherapy according to FOLFIRINOX or
T. Giuliani2, A. Di Gioia2, G. Marchegiani2, D. Melisi3,
Gemcitabine-Abraxane schedules, with tumor cannot
A. Auriemma3, C. Bassi2, M. Milella3, G. Malleo2,
exceed 5 cm in maximum diameter and without limph- R. Salvia2, R. Mazzarotto1
nodal metastases, were treated with ablative dose of 1Radiation Oncology Unit;  2General and Pancreatic
SBRT (54 Gy in 6 daily fractions) in a prospective
phase II study (NCT03158779). In selected enrolled Surgery Unit; 3Medical Oncology Unit, University of
patients, gold markers were implanted into the tumor Verona Hospital Trust, Italy
under EUS-guidance, before SBRT simulation. A new Aims: R0 resection rate in pancreatic cancer (PC)
dedicated needle was used: a 22G needle preloaded using axial slicing technique with a minimum 1-mm
with 4 gold fiducials (0.43 mm width for 5 mm length), margin for pathologic evaluation was reported from 26
EchoTip® Ultra Fiducial Needle (Cook Medical). to 32%. Preoperative Stereotactic Body Radiation
The fiducials were released under EUS guidance Therapy (SBRT) is an emerging neoadjuvant approach
and it were placed at the opposite extremities of the in patients (pts) with Borderline Resectable (BR) or
tumor. Fluoroscopy was used to confirm the position. Locally Advanced (LA) PC. This study aims to investi-
Migration, defined as a change in inter-fiducial gate the effects on surgical margins status and post-ope-
distance, was evaluated at the time of simulation phase rative complications of SBRT following induction che-
and treatment delivery. motherapy.
Results: From May 2017 to March 2019, 12 patients Methods: Pts with BR and LA PC undergoing
(8 F/4 M) aged 66.5 years (53-80 range) were enrolled induction chemotherapy and preoperative SBRT and
in LAPC02 trial and candidated to fiducials placement. selected for surgical exploration from November 2016
Induction chemotherapy was Gemcitabine-Abraxane in to November 2018 were included in the analysis. SBRT
9 patients and Folfirinox in 3 patients, with a median was delivered over 5 consecutive fractions using a
time of 4.1 months (range 3-6 months). At restaging the simultaneous integrated boost (SIB) prescribing 10
disease was still locally advanced, with no distant pro- Gy/fraction to the region of vessel abutment/encase-
gression. The tumors were localized in the head (5), ment and 6 Gy/fraction to the remaining Planning
uncinate process (3),body (3) and tail of pancreas (1). Target Volume (PTV) tumor. We reduced the dose to 5
Mean size was 31 mm (12-46 mm range). In all but one Gy/fraction on the overlap area between the PTV and
patient 2-4 markers were placed. In 5 of 12 patients pro- Organs at Risk (OARs). R0 resection was defined as the
cedure had no technical difficulties. In 7 patients, fidu- absence of microscopic tumor invasion within 1 mm of
cial placement was made difficult due to: increased resection margins, assessed by axial slicing of the sur-
hardness of lesion, nearest vessels (infiltrated portal gical specimen. Surgical complications were defined
vein or collateral vessels due to portal hypertension), according to the International Study Group of
poor control in the first marker release (two fiducials Pancreatic Surgery (ISGPS).
released in the same position). Patients started SBRT Results: The study population consisted of 44 pts. 38
with a median gap time of 10.2 days (range 6-19 days) pts underwent pancreatic resection and 6 were found to
between the fiducials placement and the first fraction. have unresectable tumor at surgical exploration, with a
Simulation included a contrast-enhanced CT scan and a resection/exploration ratio of 86.4%. R0 resection was
4D-CT scan to registered the patient’s breathing pattern. achieved in 19 pts (50% of those undergoing surgical
Slice width was 3 mm for both studies. Only one resection). Two patients were classified with a tumor
patient, in whom the simulation CT was performed at regression grade 0. Postoperative overall morbidity was
the same day of the fiducial placement, showed a mini- 54.5% and 30-days mortality was nil. Post-Operative
mal migration of one fiducial (<3 mm) when SBRT was Pancreatic Fistula (POPF) occurred in 4 pts (10.5% of
started. No severe adverse events occurred. One cases) while Post Pancreatectomy Hemorrage (PPH) was
patients presented abdominal pain responsive to parace- detected in 3 pts (8%), with one needing re-intervention.

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Conclusions: SBRT following induction chemothe- ticle therapy (IMPT) was employed. Toxicity was
rapy is a safe option in the context of a total neoadju- recorded according to CTCAE 4.0.
vant approach for BR and LA pancreatic cancer. The Results: All patients completed the scheduled treat-
rate of negative margins is promising, especially in the ment and CIRT was well tolerated. Acute toxicity was
setting of complex long-course downstaging and chal- mild, no grade 3 side effects were observed. No severe
lenging indication to surgery. late toxicity (grade 3) was scored. Two patients
underwent to surgery after CIRT with a LC of 22 and 55
months respectively after surgery and no significant
toxicities, including surgery-related were observed.
CO015
Overall, we observed local progression in 4 (25%)
patients translating into estimated 1- and 2-year local
CARBON ION RADIOTHERAPY IN LOCALLY

control (LC) rates of 71 and 55%. Metastasis Free


ADVANCED PANCREATIC CANCER TREATED AT

Survival (MFS) were reached in 43% of patients


CNAO: PRELIMINARY RESULTS
V. Vitolo1, A. Barcellini1, L. Cobianchi2,3, A. Vanoli4,
(median-MFS of 11 months ; range: 4-55 months).
M.R. Fiore1, B. Vischioni1, A. Iannalfi1, M. Bonora1,
Conclusions: In our experience, CIRT in LAPC has
S. Ronchi1, E. D’Ippolito1, R. Petrucci1, P. Fossati1,
shown a promising LC and good toxicity profile.
G. Viselner1, L. Preda1,3 S. Molinelli1, S. Durante1,5,
However, a larger series of patients and a longer follow-
F. Cuccia1,6 E. Scipilliti1,7 F. Valvo1
up are needed to better investigate outcomes, especially
1National Center of Oncological Hadrontherapy
in terms of late toxicity.
(CNAO); 2General Surgery Department, Fondazione
IRCCS Policlinico San Matteo; 3Department of
Clinical-Surgical, Diagnostic and Pediatric Sciences,
University of Pavia; 4Anatomic Pathology Unit,
CO016

Department of Molecular Medicine, University of Pavia


CLINICAL OUTCOME IN PATIENTS WITH SKULL-
and Fondazione IRCCS Policlinico San Matteo;
BASE CHORDOMA TREATED WITH PROTON AND
5University of Milan, Division of Ematology and Emato- CARBON ION RADIOTHERAPY AT CNAO:
oncology, School of Radiation Oncology; 6University of AN UPDATE
Palermo, School of Radiation Oncology; 7University G. Riva1, E. D’Ippolito2, A. Iannalfi2, S. Gandini3,
Federico II of Naples, School of Medicine, Department S. Molinelli2, M. Bonora2, M.R.F. Fiore2, B.
of Advanced Biomedical Sciences, Italy Vischioni2, V. Vitolo2, S. Ronchi2, A. Barcellini2,
R. Petrucci2, F. Valvo2
Background: Complete surgical resection is the 1University of Milan, Department of Oncology and
only curative treatment for pancreatic adenocarcinoma,
but is available only up to 15%-20% of all patients at Hemato-oncology, Milan; 2Division of Radiotherapy,
National Center of Oncological Hadrontherapy, CNAO
the time of diagnosis. In the remaining patients major
Foundation, Pavia; 3Division of Epidemiology and
vessel involvements either local tumor extension are
Biostatistics, European Institute of Oncology, Milan,
obstacles for a surgical therapy. Considering the subop-
Italy
timal efficacy of conventional therapeutic alternatives
and the consensus on the inclusion of these patients in Aims: The management of skull base chordoma is
clinical trials, locally advanced pancreatic cancer challenging, and particle therapy is the treatment of
(LAPC) could be an ideal disease to test the efficacy o choice in both adjuvant then exclusive setting. Post-
carbon ions radiotherapy (CIRT). operative radiotherapy is a predictor of improved pro-
Aim: To evaluate response and toxicity of CIRT for gression-free survival. Our purpose was to evaluate the
LAPC. long-term results in terms of local control (LC), overall
Methods: We retrospectively analyzed 16 patients survival (OS) and toxicity profile of pts with skull-base
with LAPC who have been treated with CIRT at chordoma treated with proton therapy -PT- and carbon
National Center of Oncological Hadrontherapy ion therapy –CIRT and to better identify factors influen-
(CNAO) between September 2014 and February 2019. cing clinical outcome
All patients presented a local progression after at least Methods: Between 11/2011 and 12/2018, a total of
one line of chemotherapy and 25% of patients were 146 pts where treated for skull base chordoma and 135
admitted for CIRT already in recurrent situation after patients were analyzed. Pts with follow-up <6 months
surgery. All patients will be positioned in customized were excluded.. Pts and tumors characteristics are sum-
cushions and immobilized with a solid thermoplastic marized in Table 1. Prescription dose for PT is 74
mask. A set of 2-mm-thick 4D computed tomography Gy(RBE) delivered in 37 fractions of 2 Gy(RBE), CIRT
(CT) images will be taken for treatment planning with prescription dose is 70.4 Gy(RBE) delivered in 16 frac-
the immobilization devices. The Anzai system (Anzai tions. Clinical outcome (3-5 year LC and OS rate) and
Medical, Tokyo, Japan) will be used to acquire the toxicity profile (according to CTCAE V4.03- scale)
patient breathing signal for retrospective 4D CT recon- were evaluated. Recurrent cases were retrospectively
struction. Median total dose was 57.6 GyE (range: 43.2- evaluated: the follow-up MRI sequences were the
57.6 GyE) delivered in median number of 12 fractions recurrence was detected were fused with the planning
(range: 8-12 fractions). Median dose for fraction was CT scans and data analyzed.
4.8 GyE (range: 4.6-4.8 GyE). Intensity modulated par- Results: Sixty-five pts were treated with CIRT, 70

| 55 |
Oral Communications

patients with PT. Median follow-up was 44 months L. Vicenzi15, D. Russo16, S. Borghesi17, E. Perrucci18,
(range 6-87 months). For the CIRT pts group, the 3-year S. Pignata19, C. Aristei18, M. Ferioli20,
and 5-year LC rates were 77% and 71% respectively, G. Scambia21,22, R. Autorino23,24,
relapsed occurred in 13 of 65 patients in close proxi- B.A. Jereczek-Fossa2,11, G. Ferrandina21,22
mity to brainstem or optic chiasm. The 3-year and 5- 1Fondazione Giovanni Paolo II, Unità Operativa di
year OS rates were 90% and 82% respectively. In PT Radioterapia, Università Cattolica del Sacro Cuore;
cohort the 3-year and 5-year OS rates were 90% and 2Division of Radiotherapy, IEO European Institute of
82% respectively, relapse occurred in 8 of 70 patients, Oncology, IRCCS; 3Division of Medical Gynecologic
all but one next to brainstem. The 3-year and 5-year OS Oncology, IEO European Institute of Oncology, IRCCS
rates were 93% and 83% respectively. In univariate and University of Milan-Bicocca; 4Department of
analysis the LC was significantly influenced by brain- Translational Medicine, Division of Radiation
stem/optic pathway involvement and GTV volume: Oncology, University of Pisa; 5Department of Human
GTV <10 cm3 for PT and GTV<23 cm3 for CIRT were Sciences, Society and Health, University of Cassino and
unfavorable prognostic factor for LC. High grade (G3- Southern Lazio; 6Humanitas Clinical and Research
G4) late toxicity occurred in 16 pts (12%): 2 case of Hospital - IRCSS, Radiotherapy and Radiosurgery
complete visual loss (G4) expected because of optic Dept; 7Radiation Oncology Centre, S. Maria Hospital;
nerve in field. Median time to G ≥ 3 toxicity was 21 8Department of Radiation Oncology, Campus Bio-
months (8 – 44, range). Medico University; 9Humanitas University, Department
Conclusions: Particle therapy is the most innovative of Biomedical Sciences; 10Fondazione Giovanni Paolo
and conformal RT for treatment of skull base chordo- II, Unità Operativa di Fisica Medica, Università
mas. It allows to deliver higher (biologically effective) Cattolica del Sacro Cuore; 11Department of Oncology
dose levels and to obtain high tumor control rates, with and Hemato-oncology, University of Milan; 12U.O. di
a low rate of radiation-related side effects. Radioterapia Oncologica Guido Berlucchi, Fondazione
Brainstem/optic pathway involvement and irradiation Poliambulanza; 13Radiotherapy Unit, Fondazione
tumor size is recognized as prognostic factors. IRCCS Istituto Nazionale dei Tumori; 14Department of
Radiation Oncology, San Raffaele Scientific Institute;
15Department of Oncology and Radiotherapy, Azienda

Ospedaliera Universitaria Ospedali Riuniti;


16Radiotherapy Unit, Ospedale Vito Fazzi;
Table 1.

17Radiotherapy Department, Azienda USL Toscana sud

est, San Donato Hospital; 18Radiation Oncology


Section, University of Perugia and Perugia General
Hospital; 19Istituto Nazionale Tumori di Napoli,
Fondazione Pascale IRCCS; 20Department of
Experimental, Diagnostic and Specialty Medicine -
DIMES, University of Bologna, S. Orsola-Malpighi
Hospital; 21Fondazione Policlinico Universitario A.
Gemelli, IRCCS, UOC Ginecologia Oncologica,
Dipartimento per la salute della Donna e del Bambino e
della Salute Pubblica; 22Università Cattolica del Sacro
Cuore, Istituto di Ginecologia e Ostetricia;
23Fondazione Policlinico Universitario A. Gemelli,

IRCCS, UOC di Radioterapia, Dipartimento di Scienze


Radiologiche, Radioterapiche ed Ematologiche;
24Università Cattolica del Sacro Cuore, Istituto di

Radiologia, Italy
Aims: The aim of this retrospective, multicenter
study (MITO RT-01) was to define activity and safety
of Stereotactic Body Radiotherapy (SBRT) in a very
large, real life dataset of metastatic/persistent/recurrent
CO017

ovarian cancer (MPR-OC) patients. Clinical and SBRT


A LARGE, MULTICENTER, RETROSPECTIVE
STUDY ON EFFICACY AND SAFETY OF STEREO- parameters have been analyzed in order to identify pre-
TACTIC BODY RADIOTHERAPY (SBRT) IN OLIGO- dictors of outcome.
METASTATIC OVARIAN CANCER (MITO RT1 Methods: The endpoints of the study were the rate
of complete response (CR) to SBRT, and the 24-month
actuarial local control (LC) rate on “per lesion” basis.
STUDY): A COLLABORATION OF MITO, AIRO GYN,

The secondary end-points were acute and late toxicities,


AND MANGO GROUPS
G. Macchia1, R. Lazzari2, N. Colombo3, C. Laliscia4,
G. Capelli5, G.R. D’Agostino6, F. Deodato1, and the 24-month actuarial late toxicity free survival.
F. Trippa7, E. Ippolito8, S. Ronchi2, F. Paiar4, Objective response rate (ORR) included CR and partial
M. Scorsetti6,9, S. Cilla10, R. Ingargiola2,11, response (PR). Clinical benefit (CB) included ORR and
A. Huscher12, A.M. Cerrotta13, A. Fodor14, stable disease (SD). Toxicity was evaluated by

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

RTOG/EORTC and CTC-AE scales, according to cen- target ranged from 25 to 48 Gy in 4-7 fractions; median
ter policy. Logistic and Cox regression were used for BED1.5Gy was 198 Gy (range 108.3 – 432 Gy). With a
the uni- and multivariate analysis of factors predicting median follow-up of 16 months, LC rates at 1- and 3-
clinical CR and actuarial outcomes. years were 93% and 86%, respectively. In-field pro-
Results: Fifteen Radiation Oncologist Institutions gression of disease was observed in 11 (7%) lesions.
participated to the study; after evaluation of One and 3-years NPFS was 59% and 29% and median
inclusion/exclusion criteria, 261 OC patients, carrying a NPFS was 15 months. Rates of OS at 1- and 3-years
total of 449 lesions treated by SBRT between May 2005 were 100% and 95%. The median time to the admini-
and November 2018, were selected for the enrollment. stration of a systemic treatment after SBRT was 7.8
CR, PR and SD were observed in 291 (65.2%), 106 months (1.7-54.8).
(23.8%), and 33 (7.4%) lesions, giving a rate of CB of Conclusions: SBRT is an effective and well tolera-
96.4%. Patient age <60 years, PTV <18 cm3, lymph ted treatment option in the management of lymph node
node disease, and BEDα/β10 >70 Gy were associated metastases from PCa. Prospective trials are necessary to
with higher chance of CR in the multivariate analysis. better select patients who benefit the most from this
With a median follow-up of 22 months (range: 3-120), ablative focal treatment, and better define the recurren-
the 24-month actuarial LC rate was 81.9%. ce patterns.
Achievement of CR and total dose >25 Gy were asso-
ciated with better LC rate in the multivariate analysis.
Mild toxicity was experienced in 54 (20.7%) patients:
CO019
of 63 side effects, 48 were grade 1, and 15 were grade
2. The 24- month late toxicity free survival rate was
EXTENDED OR FOCUSED RADIOTHERAPY IN

95.1%.
OLIGO-METASTATIC/OLIGO-RECURRENT PROSTA-

Conclusions: This study confirms the activity and


TE CANCER: LONG TERM CANDIOLO EXPERIENCE
E. Garibaldi1, A. Di Dia2, G. Cattari1, G. Belli1,
safety of SBRT in MPR-OC patients and identifies cli-
D. Gabriele3, P. Scapoli4, C. Baiocco5, J. Di Muzio1,
nical and treatment parameters able to predict CR and
P. Gabriele1, M. Gatti1
LC rate.
1Radiation Oncology Unit, Candiolo Cancer Institute,

Candiolo (TO); 2Medical Physics Unit, Candiolo


Cancer Institute, Candiolo, 3Radiation Oncology Unit,
Sassari University H, Sassari; 4Nuclear Medicine Unit
CO018

Candiolo Cancer Institute and 5Nuclear Medicine Unit


RECURRENCE PATTERN OF STEREOTACTIC BODY
Parini Regional H, Aosta, Italy
RADIOTHERAPY (SBRT) IN OLIGOMETASTATIC

Aims: Recent technology advances in diagnostic


PROSTATE CANCER: A MULTI-INSTITUTIONAL

and radiotherapy (RT) field have allowed to early detect


ANALYSIS
L. Nicosia1, C. Franzese2, R. Mazzola1,
D. Franceschini2, M. Rigo1, G. D’agostino2, and early treat oligo-metastasis/oligo-recurrences pro-
S. Corradini3, F. Alongi1,4, M. Scorsetti2 state cancer (OMPC) paients (pts). The aim of this
1Radiation Oncology, IRCCS Sacro Cuore Don paper is to present our experience in RT of OMPC pts
focusing on local-locoregional control, toxicity and
Calabria Hospital, Negrar-Verona, Italy; 2Radiotherapy
time to recurrence.
and Radiosurgery Department, Humanitas Clinical and
Methods: From October 2010 to December 2018,
Research Hospital, Milan-Rozzano, Italy; 3Radiation
we treated 61 pts [mean age (min-max): 61 (45-77),
Oncology Department, University Hospital, LMU
Karnofsky: 80-100] with node and/or bone recurrences
Munich, Munich, Germany; 4University of Brescia, Italy
from prostate cancer. All patients received functional
Purpose: For patients with oligometastatic/oligore- imaging (by 68Ga-PSMA ligand /CT-PET in 21
current/oligoprogressive lymph node metastases from patients, 18 choline /CT-PET in 40 pts and also multi-
PCa, metastases-directed therapy is an emerging stra- parametric MRI in 6 patients). Pts were treated accor-
tegy. The aim of this retrospective study was to evaluate ding our Internal protocol and they signed an informed
the oncological outcome and pattern of recurrence of consent form. The recurrence sites were nodal in 57
patients treated with stereotactic body radiation therapy (pelvic in 36 pts, lumbar aortic in 21 pts), bone in 4 pts.
(SBRT) on lymph node metastases. For each pts number of metastases ranged between 1
Methods: In this multi-institutional analysis, and 5 (mean 2.5) for group 1 (extended RT) and
patients with maximum 5 lymph node metastases from between 1 and 2 lesions for group 2 (focused RT) .
PCa treated with SBRT were included. Primary end- Thirty-nine pts (group 1) were treated by IMRT-SIB-
points of the analysis were local control (LC), out-of- IGRT with Tomotherapy on regional node with prophy-
field nodal progression-free survival (NPFS), overall lactic doses (range 51-54 Gy – 1.7-1.8 Gy per fraction)
progression-free survival (PFS) and overall survival and on positive nodes from 66Gy (2.2 Gy per fraction)
(OS). to 70,5 Gy, (2.35 Gy per fraction). Twenty-two pts
Results: 109 patients and 155 lymph node metasta- (group 2) were treated with targeted RT on lesions by
ses were evaluated. Patients’ median age was 70.8 years Tomotherapy (18 pts) (doses: 24-30 Gy in 4-5 fractions)
(range, 51-84) and median PSA before SBRT was 1.88 or SBRT LINAC-based (4 pts) (doses 18-24 Gy in sin-
ng/ml (range, 0.3-45.5 ng/ml). The dose delivered to the gle fraction).

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Oral Communications

Results: No GU/GI acute or late toxicity >G2 18m. 38 pts relapsed in the treatment field, 91 pts in the
(RTOG scale) were observed in both groups. All con- chest and 246 showed extra pulmonary recurrences.
straints for normal tissues were respected according to Statistically significative differences on OS was obser-
QUANTEC. The mean follow up was 51 months (range ved between patient with primary controlled or not (2y,
10-91) in the group 1 and 18,4 months (range 6-29) in OS 88% vs 60%), with metachronous vs synchronous
the group 2. In the group 1, 6 pts dead for progression metastases (2y, OS 97% vs 63%), chemotherapy or not
disease and 5 were lost at follow up; local control (LC) after SBRT (2y, OS 86% vs 52%). 5y OS for patients
and loco-regional control (LRC) were 96.7% and 75% treated for breast metastases was 87%, for colorectal
respectively, and the average time to recurrence was 24 cancer 51% and for NSCLC 61%. No significant diffe-
months (range 3-91); the site of recurrence was loco- rences on LC was detected between different primary
regional in 15 pts, bone in 3 pts and both in 2 pts; 4 pts tumors. LC rates appears relate only to BED value.
developed visceral and nodal metastases. In the group Toxicity was mild and not exceeded the grade 2.
2, LC was 100% and average time to recurrence was 6.7 Conclusions: SBRT appears as safe and effective
months (range 1-13). The sites of recurrence in this therapy showing high rate of LC of pulmonary metasta-
group was loco regional (pelvic) in 7 pts; to date, 3 pts ses using BED value exceeding 100Gy. The influence
showed biochemical relapse. on OS appears to be related to the time of metastases
Conclusions: To date, our data show better results in appearance (synchronous vs metachronous), primary
terms of time to recurrence in the group of extended RT tumor controlled or not and the use of chemotherapy
compared to targeted RT, despite similar LC and treat- after SABR. The rate of OS, confirms the possibility to
ment tolerance, suggesting that targeted RT do not use of SABR with curative intent in well selected oligo-
always translates into a good oncological results and metastatic patients. The better rates of OS occurs in pts
that each case needs a multidisciplinary evaluation. treated for breast and lung cancer. The majority of fai-
Moreover, two groups are not comparable in terms of lures was represented by extra thoracic spread, leading
follow-up time, and a longer follow up is necessary for to necessity of more effective systemic therapies.
group 2.
CO021
CO020
STEREOTACTIC FRACTIONATED RADIOTHERAPY
SBRT FOR OLIGOMETASTATIC PATIENTS ON THE IN CHOROIDAL METASTASIS
LUNG. A MONO-ISTITUTIONAL EXPERIENCE ON G. Polizzi1, P. Ricci1, A. Grimaldi1, M. Cavallari1,
C. Schiavone1, S. Sacco1, G. Siffredi1, G. Coscia2,
R. Corvisiero2, C. Mosci3, F. Grillo Ruggieri1
987 TREATED LESIONS
E. Lombardo, C. Menichelli, A. Fanelli, G. Pastore,
E. Paulicelli, F. Casamassima Scuola di Specializzazione in Radioterapia, Università
Ecomedica, Empoli, Italy degli Studi di Genova, Italy
Aims: Patients with oligometastases to the lung Aim: The purpose of this study is to demonstrate
from solid tumors are now considered candidates for safety and feasibility of Stereotactic Fractionated
curative therapy. Uncertainties on the patients selection Radiotherapy[SRT] in choroidal metastatic patients and
and the relationship with systemic therapies are still not to evaluate clinical outcomes in terms of local control
well defined. We study the results in terms of LC, OS, and toxicity.
toxicity and progression modality in 409 pts treated Materials and Methods: Thirty-six pretreated
whit SBRT for pulmonary oligometastases from diffe- patients [pts] were evaluated: one had histological con-
rent primary tumors. firmation, the others had a clinical and/or radiological
Methods: Between December 2010 and December diagnosis. Eye examination, Ultrasound and Ocular
2018, 456 pts were treated with SBRT on 987 lesions. Computed Tomography were performed in every
Primary cancer was lung in 42%, colorectal in 27%, patient to evaluate visus. All of them received SRT +
breast in 6%, H&N in 3%, Kidney in 4% and 18% Photo-Dynamic Therapy between November 2009 and
others. All lesions was contured on CT scan data sets August 2017. Thirteen patients were males (36%), 23
acquired in supine position using wing board and dual were female (64%); 15 of 36 had bilateral localizations
legs. CT was acquired in breath hold using Active (42%), with 51 eyes overall treated. Nine patients
Breathing Coordinator device in 354 pts, for 48 pts was (25%) received a boost on small volumes. Median age
used a 4D CT. Treatments were planned using MONA- is 61,5 (34-85), median follow-up 11,5 months (2-64).
CO TPS with Montecarlo optimization algorithm. Primary tumor site was breast cancer (17/36, 47%) and
Median target volume was 3,24 cc. The median dose of lung carcinomas (12/36, 33%); the remaining were
33,2 Gy was prescribed to 70% isodose with median esophageal, HCC, kidney, bladder, prostate and pan-
BED at the isocenter of 118Gy in 1 to 3 fx (median 3fx). creatic carcinomas. All pts were pretreated with che-
Treatment was delivered by 6MV Linac . Set-up and motherapy; 31/36 (86%) had also extraocular metasta-
isocenter position assessed by CBCT. Toxicity was eva- sis. CT scan was performed in every pts and 4/36 (11%)
luated using CTCAE v 4.0 underwent MR. Localization was performed with
Results: With median follow up of 22 months, Leksell Type relocatable Stereotactic Frame (BrainLab,
median OS was 56m, DFS was 16m and median LC Germany). The CTV included all choroid and macro-

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scopical lesions; 3mm isotropic expansion was added to 1, 2-year OS rates were 22 months (95%CI20-
CTV to define PTV. Omolateral lacrimal glands was 30months), 95%±2.1%, 81.9%±3.8%, and 46.6%±6%.
partially, if possible, excluded from PTV. Acute radia- Infratentorial site, residual-tumor-volume, longer inter-
tion-induced toxicity was assessed according to RTOG val time between primary diagnosis and occurrence of
scales; as Organ at Risk, conjuntival mucosa, lacrimal BMs, and oligometastatic disease status significantly
glands, brainstem, brain and lens were evaluated. RT influenced outcome. Grade 2-3 radionecrosis occured
treatments were non-coplanar 3D Conformal RT in 26 patients. Neurocognitive functions remained sta-
(21/36,58%), Step-and-shoot Intensity Modulated RT ble or in some cases improved.
[IMRT] (10/36, 28%) and Arc-Therapy (5/36, 14%). Conclusions: Surgery followed by HSRS on the
Results: All pts completed the prescribed treatment. tumor bed, is a safe and effective approach, affording
Total dose ranged from 12 to 36 Gy (median 30 Gy), good brain control with negligible toxicities. BMs does
number of fractions was between 5 and 18; boost was not always define a disease with worse prognosis, pro-
from 0,75 to 12 Gy. Median BEDGy10 was 35.01Gy10 vided that a really ablative local treatments is carried
(15,6-44,8), Median BEDGy3 was 50Gy3 (24-60). out.
Response rate resulted in: Complete Response 4/36
(11%), Partial Response 15/36 (42%), Stable Disease
12/36 (33%), Progression Disease 5/36 (14%). Toxicity
CO023
was low: G3 adverse event, consisting in severe conjun-
tival hyperemia, has occurred in 1/36 pts(3%).
RADIOSURGERY (SRS) REIRRADIATION OF

Conclusions: Stereotactic Fractionated


BRAIN METASTASIS (BM) FROM BREAST CANCER
P. Anselmo, M. Casale, S. Terenzi, F. Trippa,
Radiotherapy in choroidal metastases is a feasible and
F. Arcidiacono, L. Draghini, A. Di Marzo,
safe procedure, characterized by low toxicity and by the
E. Maranzano
possibility to spare most of the optical nerves and the
whole brain. Radiotherapy Oncology Centre, S. Maria Hospital,
Terni, Italy
Purpose: To assess the clinical outcome and toxicity
of reirradiation with SRS after prior WBRT, as a salva-
CO022

ge treatment for progressive BM in patients with meta-


static breast cancer.
SURGERY FOLLOWED BY HYPOFRACTIONATED

Methods: From December 2001 to December 2017,


RADIOSURGERY ON THE TUMOR BED IN OLIGO-

128 patients with 259 recurrent BM after WBRT were


METASTATIC PATIENTS WITH LARGE BRAIN

reirradiated with SRS. In this report, we have retrospec-


METASTASES. RESULTS OF A PHASE II STUDY
I. Renna, E. Clerici, P. Navarria, F. Pessina,
G. D’Agostino, C. Franzese, D. Franceschini, tively analyzed only patients with brain metastatic brea-
T. Comito, F. De Rose, L. Di Brina, A. Tozzi, C. Iftode, st cancer (BMBC).
M. Scorsetti Results: 35 BMBC patients with 79 BM were stu-
died. Median age was 55 years (range, 35-82). 21 (60%)
Istituto Clinico Humanitas, Rozzano, Italy
patients were HER +, of which 7 (33%) and 14 (67%)
Aims: This prospective phase II study assessed were ER- and ER+, respectively. 5 (14%) patients were
safety and feasibility of surgery followed by hypofrac- triple-negative while the remaining 9 (26%) had a lumi-
tionated radiosurgery (HSRS) on the tumor bed in oli- nal-like breast cancer. 15/21 (71%) of HER+ patients,
gometastatic patients with single large brain metastases received trastuzumab between WBRT and SRS, in all
(BMs). cases targeted therapy was stopped at least 7 days befo-
Methods: Between June 2015 and May 2018 101 re reirradiation. The median KPS was 100 (range, 60-
patients were enrolled. Oligometastatic disease was 100), 30 (86%) patients had a Neurological functional
defined by a maximum of 5 metastatic lesions. status (NFS) of 0, 4 (11%) and 1 (3%) a NFS of 1 and
Hypofractionated radiosurgery on the tumor bed inpla- 2, respectively. 29 (83%) patients had a controlled
ced of WBRT. HSRS was performed within 1 month extracranial disease. Median time between WBRT and
from surgery and consisted of 30 Gy/3 fractions.. Local SRS was 16 months (range, 2-92). The median number
control, occurrence of new BMs, overall survival, and of reirradiated BM was 2 (range, 1-4) and the median
treatment related toxicities were assessed. tumor volume was 0.9 cc (range, 0.1-18.6). Prior
Results: At a median follow up time of 26 months WBRT doses ranged from 10 fractions of 3 Gy (66%)
local recurrence occurred in 6 (5.9%) patients. Six- and 5 fractions of 4 Gy (34%), SRS re-treatment
month, 1, 2-year local control rates were 100%, median dose was 18 Gy (range, 15-25). Three months
98.9%±1.1%, 85.9%±0.6%. New BMs occurred in 39 after reirradiation, 9 (11%) BM were in complete remis-
(38.6%) patients; median brain-distant-progression sion, 19 (24%) in partial remission, 49 (62%) were sta-
time, 6-month 1, 2-year brain-distant-progression rates ble and only 2 (3%) progressed, resulting a brain con-
were 39 months (95%CI 19-39months), 17%±3.7%, trol of 97%. 17 (48.5%) patients had an out-field rela-
31.4%±4.8%, and 42.5%±5.9%. At the last observation pse after a median time of 12 months (range, 3-34): 5
time 50 (49.5%) patients are alive and 51 (50.5%) dead; (29%), 2 (13%), 5 (29%) and 5 (29%) patients received
10 patients died for neurological cause and 40 for syste- SRS, WBRT, chemotherapy, and supportive care,
mic progression. Median overall survival time, 6-month respectively. Among patients with out-field relapse: 9

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(53%) were HER+, 3 (18%) triple-negative and 5 Disease recurrence or progression after SBRT occurred
(29%) Luminal-like. At the time of analysis, all patients in 51 (34,9%) patients. A median disease-free interval
have died: 15 (43%) for brain progression, 10 (28.5%) from SBRT to recurrence or progression was 13 months
for systemic progression and 10 (28.5%) for both cra- (range 2-52). No patients experienced acute toxicity of
nial and systemic progression. The median OS from grade ≥2 or other late adverse events. When the
reirradiation with SRS was 14 months (range, 3-82), 12, dose/fraction was higher than 8 Gy a prophylactic the-
14 and 15 months in HER+, triple-negative and lumi- rapy with steroids was proposed. The 2-years OS was
nal-like patients, respectively. No acute and/or late toxi- 64%.
cities were registered. Conclusions: Hypofractionated SBRT is an effecti-
Conclusions: Reirradiation with SRS is an effective ve tool in the management of patients with pulmonary
and a safe treatment for selected BMBC patients. metastases. Even if lesions from different primaries
Patients selection should be based on good KPS and were treated using various fractionation schedules and
NFS, controlled extracranial disease and 1 to 4 BM. modalities, SBRT achieved acceptable tumor control
with minimal toxicities. Our results suggest that a care-
ful patient selection would be desirable in to determine
the benefit of this treatment option.
CO024
HYPOFRACTIONATED STEREOTACTIC BODY
RADIATION THERAPY (SBRT) IN THE TREATMENT CO025
OF PULMONARY METASTASES: A SINGLE INSTI-
TUTION EXPERIENCE FROM A TERRITORIAL ABSTRACT WITHDRAWN
HOSPITAL
D. di Cristino1, F. Salerno1, A. Ciabattoni1, F. Vidiri1,
A. Corbosiero1, M.C. Fares1, T. Palloni1,
A. Siniscalchi1, K.J. Llange1, R. Conforti2,
CO026

M.A. Mirri1 THE DOSIMETRIC IMPACT OF AXILLARY NODES


1UOC Radioterapia, P.O. San Filippo Neri, ASL Roma
CONTOURING VARIATION IN BREAST CANCER
1; 2UOSD Fisica Sanitaria, P.O. San Filippo Neri, ASL M.C. Leonardi1, F. Cattani2, R. Luraschi2, S. Vigorito2,
Roma 1, Italy M. Pepa1, S.G. Gugliandolo1, M.R. La Porta3,
D. Cante3, E. Petrucci3, L. Marino4, G. Borzi4,
Aims: To retrospectively analyze the feasibility and E. Ippolito5, M. Marrocco5, A. Husher6,
the efficacy of Stereotactic Body Radiation Therapy M. Chieregato6, A. Argenone7, L. Iadanza7,
(SBRT) in the treatment of pulmonary metastases from F. De Rose8, F. Lobefalo8, F. Cucciarelli9, M. Valenti9,
multiple primary cancers. M.C. De Santis10, A. Cavallo10, F. Rossi11, S. Russo11,
Methods: Between January 2010 and December A. Prisco12, M. Guernieri12, R. Guarnaccia13,
2018, 146 patients (54 female, 92 male) were treated T. Malatesta13, I. Meaglia14, M. Liotta14, I. Palumbo15,
with SBRT (169 lesions). Median age was 72 years M. Marcantonini15, S.P. Colangione16, E. Mezzenga16,
(range 43-90) and Karnofsky PS ≥ 70. Different doses S. Falivene17, M. Mormile17, V. Ravo18,
and fractionation were used, based on patient’s status, C. Arrichiello18, A. Fozza19, M.P. Barbero19,
respiratory conditions, volume and site of the lesions. G. Ivaldi14, G. Catalano20, C. Vidali21, C. Aristei15,
Irradiation was performed with 6 to10 MV X-ray beams C. Giannitto22, D.Ciardo1, R. Orecchia23,
from a LINAC Trilogy by Varian Medical Systems. B.A. Jereczek-Fossa1,24
Used techniques were conformal dynamic arcs, IMRT 1Division of Radiation Oncology, Istituto Europeo di
or VMAT. From 2016, a Maximum Intensity Oncologia, Milano; 2Department of Medical Physics,
Projections (MIP) was performed for target volume Istituto Europeo di Oncologia, Milano; 3Radiotherapy
generation in 4D CT scans. Used Treatment Planning Department, Ivrea Community Hospital, Ivrea;
System was Ray Station 4.5 or Pinnacle 9.10. Toxicity 4Radiotherapy Department, Istituto Oncologico del
was evaluated using the CTCAE 4.03. Response, pro- Mediterraneo, Catania; 5Department of Radiotherapy,
gression or stable disease (SD) were defined according Campus Bio-Medico University, Roma; 6Radiotherapy
both to RECIST criteria and respiratory function. Unit, Fondazione Poliambulanza, Brescia; 7Division of
Results: Treated sites were metastases from primary Radiation Oncology, Azienda Ospedaliera di Rilievo
lung cancer (93), colorectal (22), kidney (9) and others Nazionale g. Rummo, Benevento; 8Radiotherapy and
(22). Twenty five (17,1%) patients were treated on more Radiosurgery Department, Humanitas Cancer Centre
than one lesion. The patients reported in this analysis and Research Hospital, Milano; 9Department of
were considered unfit for surgery due to medical con- Internal Medicine, Radiotherapy Institute, Ospedali
traindications. Median SBRT dose was 40 Gy (range Riuniti Umberto I, G.M. Lancisi, G. Salesi, Ancona;
16-50 Gy) mainly in 5 fractions (range 1-8). Median 10Radiotherapy Unit 1, National Cancer Institute of
follow-up was 12 months (range 1-86). No patients pre- Milan; 11Radiotherapy Unit, Azienda Sanitaria 10,
sented complete radiological response. A radiological Firenze; 12Department of Radiotherapy, Azienda
partial response and stable disease (SD) were documen- Sanitaria Universitaria Integrata Santa Maria della
ted in 46 (31,5%) and 49 (33,6%) patients respectively. Misericordia, Udine; 13Radiotherapy Unit, Ospedale
A respiratory improvement was observed in all of them. Fatebenefratelli Isola Tiberina, Roma; 14Department of

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Radiation Oncology, Fondazione Salvatore Maugeri, higher than GSPTV V95.


Pavia; 15Radiation Oncology Section, University of Conclusions: Axillary nodes CTV delineation varia-
Perugia and Perugia General Hospital, Perugia; tion led to significant reductions in dose delivered to
16Department of Radioterapy, Istituto Scientifico
GSPTV. No plans achieved acceptable GSPTV covera-
Romagnolo per lo Studio e la Cura dei Tumori, ge, as V95 was always lower than 90%. The poor ideal
Meldola; 17Department of Radiotherapy, ASL Napoli 1 plan coverage outlined the dosimetric impact of axillary
Centro - Ospedale del Mare, Napoli; 18Division of nodes contouring variability and the need for delinea-
Radiotherapy, Istituto Nazionale per lo Studio e la Cura tion training and standardization.
dei Tumori, Fondazione G. Pascale IRCCS, Napoli;
19Division of Radiation Oncology, Azienda Ospedaliera

Nazionale SS. Antonio e Biagio e Cesare Arrigo,


Alessandria; 20Radiotherapy Department, Ospedale
Multimedica Castellanza, Castellanza (VA); 21S.C.
Table 1. Dosimetric results for the axillary nodal SCPTV and GSPTV of the three

Radioterapia, Azienda Sanitaria Universitaria Integrata


patients analysed

di Trieste (ASUI-TS), Trieste; 22Division of Radiology,


Istituto Europeo di Oncologia, Milano; 23Scientific
Direction, European Institute of Oncology, Milano;
24Department of Oncology and Hemato-Oncology,

University of Milan, Milano, Italy


Aims: To investigate the dosimetric impact of axil-
lary nodes contouring variation in breast cancer (BC).
Methods: 19 radiotherapy (RT) centres were asked
to create the planning target volume (PTV), named as
Single Centre PTV (SCPTV) from the clinical target
volume (CTV) they had delineated in a previous inve-
stigation, (Single Center CTV,SCCTV) and to plan the
locoregional treatment. The SCCTV comprised the
axillary nodes of 3 BC patients with different anatomy,
CO027

candidate to receive RT. The 3 corresponding gold stan-


dard (GS) CTVs (GSCTV) were created from a consen-
SURVEY IN RADIATION ONCOLOGY CENTRES OF

sus using the STAPLE algorithm. For each patient, the


TUSCANY AND UMBRIA REGIONS ON ADJUVANT

GS PTV (GSPTV) was obtained by applying each sin-


RADIOTHERAPY IN BREAST CANCER: INDICA-

gle centre’s CTV to PTV margins to the GSCTV. The


TIONS, VOLUMES, FRACTIONATION
S. Borghesi1, F. Rossi2, P. Bastiani2, M. Alessandro3,
following Dose Volume Histogram (DVH) parameters P. Anselmo4, C. Aristei5, R. Bagnoli6, M. Bosio7,
for each centre’s SCCTV, GSCTV, SCPTV and GSPTV F. Casamassima8, A. Corsini7, M. Crociani9,
of the 3 patients were compared: dose delivered to 99%, G. Francolini10, G. Iovini11, V. Marchetti12,
98%, 95%, 2% and 1% of the volume (D99, D98, D95, I. Meattini10, F. Paiar13, C. Polli14, S. Saldi5,
D2, D1, respectively), the mean dose delivered P. Tini9, F. Trippa4, E. Vezzani15
(Dmean) and the volume receiving 95% of the dose 1Radioterapia, Ospedale San Donato; 2Radioterapia,
(V95). Statistical analysis included mean value, stan-
Ospedale S.M. Annunziata; 3Radioterapia - Ospedale di
dard deviation (SD), 95% confidence intervals (95%
Città di Castello; 4Radioterapia - Azienda Ospedaliera
CI) and p-value.
S.Maria; 5Radioterapia - Azienda Ospedaliera-
Results: Data are available for 18 out of 19 centres.
Università degli Studi di Perugia; 6Radioterapia,
Seventeen centres used Intensity Modulated RT. The
Presidio Ospedaliero San Luca; 7Radioterapia, Spedali
CTV to PTV margins ranged from 0 to 10 mm (median,
Riuniti; 8Radioterapia, Istituto di Ricerche Cliniche
5 mm). Each centre’s DICOM dose distribution, struc-
Ecomedica; 9Radioterapia, Policlinico Le Scotte -
ture set and corresponding computed tomography (CT)
Università degli Studi di Siena; 10Radioterapia, Azienda
data were imported into MIM v6.1.7 [MIM Software
Ospedaliero-Universitaria di Careggi - Università degli
Inc.]. Results are shown in Table 1. GSPTV Dmean was Studi di Firenze; 11Radioterapia, Ospedale
on average 4% of prescribed dose lower than that of Misericordia; 12Radioterapia, Civico Ospedale;
SCPTV. Considering all patients, the mean difference in 13Radioterapia, Azienda Ospedaliera-Universitaria
D99, D98 and D95 between the SC-PTV and GS-PTV Pisana; 14Radioterapia, Casa di Cura Villa Fiorita;
was statistically significant, ranging from 22.24% to 15Radioterapia, Nuovo Ospedale S. Jacopo, Italy
34.30%. Mean D2 was always lower than 107%, both
for GSPTV and SCPTV, while mean D1 was higher Aims: On behalf of the Italian Association of
than 105% only in one patient. SCPTV V95 was always Radiation and Clinical Oncology (AIRO), the Tuscan -
higher than 90%, whereas GSPTV V95 was always Umbrian Section conducted a survey to evaluate the
lower than 90%. By analyzing results related to CTV, it management of drainage lymph nodes in breast cancer
has been found that, on average, the GSCTV coverage (BC) patients, in order to identify practice patterns.
was better than the GSPTV coverage, as the GSCTV Methods: an electronic questionnaire was sent to all
V95 was respectively 12.18%, 10.57% and 10.95% Radiation Oncology Centers in Tuscany and Umbria,

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Oral Communications

with three clinical cases, which could be included in the Diagnostics - Cardiothoracic & Vascular, Azienda
so-called "gray areas", asking for: 1. whether radiothe- Ospedaliero Universitaria Careggi, Firenze; 3SOC
rapy (RT) was indicated or not 2. if drainage lymph Oncologia Medica, Azienda USL Toscana Centro,
nodes (supra/infraclavicular and/or axillary nodes) Firenze; 4Cancer Risk Factors and Lifestyle
should be included in treatment volume 3. which Epidemiology Unit, Institute for cancer research, pre-
dose/fractionation should be advisable. vention and clinical network (ISPRO), Firenze; 52nd
Results: A total of 15 questionnaires were returned. Medical Oncology Division, Department of Oncology,
For case 1, RT after mastectomy and lymph node dis- AOU Città Della Salute e Della Scienza, Torino;
section (LND) for infiltrating lobular carcinoma pT1c 6Oncologia, Dipartimento Oncologico - Azienda USL

(m) pN1a (2/4), G3 ER 98%, PgR 100%, Ki 67 45%, Toscana Nord Ovest, Livorno; 7Medical Oncology,
cerB2 negative, was proposed in only 7/15 cases Ospedale Versilia USL12, Lido Di Camaiore; 8U.O.C di
(46.6%). The majority would irradiate wall and draina- Medicina Interna Internistica ad indirizzo di Continuità,
ge lymph nodes excluding the axillary nodes (AN). Ospedale San Giuseppe, Empoli; 9Breast Surgery Unit,
Conventional fractionation was chosen by all the Azienda Ospedaliero Universitaria Careggi, Firenze;
Centers except for one that would prefer hypofractiona- 10Diagnostic Senology, Azienda Ospedaliero
tion (40 Gy/15 fractions). The bolus was used only by 2 Universitaria Careggi, Firenze, Italy
Centers. For case 2, RT after breast conservative sur-
gery (BCS) and sentinel node biopsy (SNB) for infiltra- Aims: SAFE trial (NCT2236806) is a phase 3 study
ting ductal carcinoma with neoplastic diffusion at 3 of comparing the effect on subclinical heart damage of
the 5 removed sentinel lymph nodes (SNs), of which 1 bisoprolol (B), ramipril (R), or both drugs (R+B), as
macro and 2 micrometastatic SNs, pT1cpN1a (3/5), G2 compared to placebo (P), in breast cancer treated with
ER95%, PgR 30%, Ki 67 18%, cerB2 negative, was (neo)adjuvant anthracyclines +/- trastuzumab.
proposed in all cases. Six over 15 Centers would inclu- Methods. Primary endpoint is subclinical cardio-
de in RT volume the supra/infraclavicular nodes (S/I toxicity measured with echocardiography and global
Ns) and of these, 5 would also irradiate the AN. linear strain (GLS). This interim analysis was pre-spe-
Conventional fractionation was chosen by all the cified on the first 120 patients who had completed car-
Centers except for 4. For case 3, RT after neoadjuvant diological assessments at 12-mos. Stopping rules per
chemotherapy, BCS and LND for multifocal infiltrating arm were: dose reduction >15%, study withdraw rate
ductal carcinoma with 1 macrometastatic and 1 micro- >5%, and no significant impact on 3D-left ventricular
metastatic lymph node out 18, ypT2 ypN1a (2/18), G2 ejection fraction (3D-LVEF) as compared to T0 at 12-
ER 100%, PgR 60%, Ki 67 15%, cerB2 negative, was mos assessment.
proposed in all cases. The majority (12 Centers) would Results: A total of 191 out of 480 patients have
include in RT volume the S/I Ns and of these, 4 would been enrolled; overall 123 patients were available for
also irradiate the AN. Conventional fractionation was the analysis (P=34; R=28; B=31; R+B=30). GLS
chosen by all the Centers except for 3. increased at 3-mos (5.7%; p<0.001), at 6-mos (7.8%;
Conclusions: This survey illustrates the very diffe- p<0.001) and at 12-mos (7.1%; p<0.001) respect to T0
rent current practice patterns for management of draina- in P; at 3-mos (2.7%; p=0.002), at 6-mos (3.2%;
ge lymph nodes in 15 Radiation Oncology Centers in p=0.014), but not at 12- mos in R; no significant chan-
Tuscany and Umbria. This difference reflects an impor- ges at 3-mos, a significant increase at 6-mos (2.7%;
tant limit that exists today due to the lack of consolida- p=0.035), at 12-mos (3.2%; p=0.008) in B; no signifi-
ted data. More clinical trials and collaboration are nee- cant changes at 3-, 6-, and 12-mos in R+B. Arm diffe-
ded. rences were significant (p=0.002). Both R+B and the R
arms showed a withdraw rate of 7%, with a dose reduc-
tion rates of 21% and 17%, respectively. 3D-LVEF
CO028 decreased at 3-mos (-3.3%; p<0.001), at 6-mos (-5.2%;
p<0.001) and at 12-mos (-3.7%; p=0.004) respect to T0
in P; at 3-mos (-2.4%; p=0.001), at 6-mos (-1.9%;
PRE-SPECIFIED INTERIM ANALYSIS OF THE

p=0.010), at 12-mos (-2.2%; p=0.045) in R. In B and


SAFE TRIAL: A 4-ARM RANDOMIZED, DOUBLE-
R+B patients no significant changes were observed at
BLIND, CONTROLLED STUDY EVALUATING THE
3- and 12-mos, with a decrease at 6-mos (-2.5% and
EFFICACY AND SAFETY OF CARDIOTOXICITY
3.0%, respectively; p=0.002). Arm differences were
PREVENTION IN NON- METASTATIC BREAST
significant (p=0.038). R arm showed a significant
CANCER PATIENTS TREATED WITH ANTHRACY-
CLINES WITH OR WITHOUT TRASTUZUMAB decrease on 3D-LVEF at 12-mos as compared to T0 and
P. Garlatti1, I. Meattini1, I. Desideri1, V. Scotti1, will be evaluate for closure.
C. Becherini1, F. Terziani1, G. Barletta2, F. Martella3, Conclusions: At the interim analysis, a cardiopre-
C. Bacci3, C.Saieva4, M. Airoldi5, G. Allegrini6, ventive treatment significantly decrease subclinical
D. Amoroso7, F. Venditti2, R. Tarquini8, L. Orzalesi9, heart damage; definitive results will be useful to define
L. Sanchez9, M. Bernini9, J. Nori10, L. Fioretto3, the most effective treatment.
L. Livi1
1Department of Biomedical, Experimental, and Clinical

Sciences, University of Florence, Firenze; 2Cardiology

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

region according to Japan Pancreas Society classifica-


tion. PTV includes the CTV with a 5-mm margin to
CO029

account for set up uncertainties and residual tumor


motion. The Anzai system will be used to acquire the
ABSTRACT WITHDRAWN

patient breathing signal for retrospective 4D CT recon-


struction and treatment plans will be optimized on the
CO030
CT scan corresponding to the maximum expiration
phase. Treatment is performed combining gating and
FEASIBILITY RESULTS OF PHASE II CLINICAL

rescanning with a ≈1s gating window centered around


STUDY FOR THE PREOPERATIVE TREATMENT OF

the maximum expiration phase. Patients will receive


OPERABLE OR BORDERLINE OPERABLE PAN-

CIRT at the dose of 38.4 GyRBE carried out in 8 frac-


CREATIC ADENOCARCINOMA WITH CHEMOTHE-

tions, 4 fractions per week. Before surgery, restaging


RAPY AND CARBON ION HADRONTHERAPY
CT scans will be performed to evaluate resectability
(PIOPPO TRIAL)
V. Vitolo1, A. Barcellini1, L. Cobianchi2,3 , and absence of systemic progression. 4 to 6 weeks after
A. Vanoli4, A. Facoetti1, S. Brugnatelli5, A. Peloso6,7, the completion of CIRT, patients will undergo pancrea-
P. Dionigi2,3, S. Molinelli1, C. Klersy9, P. Fossati1, ticoduodenectomy (for tumors of the pancreatic head)
S. Delfanti5, P. Fossati1, M.R. Fiore1, B. Vischioni1, or distal pancreatectomy and splenectomy (for tumors
A. Iannalfi1 , R. Petrucci1 M. Bonora1, S. Ronchi1, of the body/tail). Tumor regression grade will be eva-
E. D’Ippolito1, G. Viselner1, F. Cuccia1,10, luated according to Evans score. Adjuvant chemothe-
S. Durante1,11 E. Scipilliti1,12 F. Valvo1 rapy will be expected from 30 to 40 days after surgery
1National Center of Oncological Hadrontherapy
as expected in clinical practice.
(Fondazione CNAO), Italy; 2General Surgery Results: Since January 2018 six patients have been
Department, Fondazione IRCCS Policlinico San so far enrolled and five have completed the surgical
Matteo, Italy; 3Department of Clinical, Surgical, phase. No significant acute toxicities, including sur-
Diagnostic and Pediatric Sciences, University of Pavia, gery-related were observed.
Italy; 4Anatomic Pathology Unit, Department of Conclusions: Our preliminary results suggest that
Molecular Medicine, University of Pavia and CIRT does not affect negatively the surgical approach.
Fondazione IRCCS Policlinico San Matteo, Italy; Our results provide initial evidence of the feasibility of
5Department of Oncology, Fondazione IRCCS the combined chemotherapy and CIRT in the neoadju-
Policlinico San Matteo, Italy; 6Hepatology and vant setting for Rpc or BRpc.
Transplantation Laboratory, Department of Surgery,
Faculty of Medicine, University of Geneva, Geneva,
Switzerland; 7Divisions of Abdominal and CO031
Transplantation Surgery, Department of Surgery,
Geneva University Hospitals, Geneva, Switzerland;
PREOPERATIVE SHORT-COURSE RADIOTHERAPY
8Weil Cornell Radiation Oncology,9Biometry and FOLLOWED BY DELAYED SURGERY IN ELDERLY
Statistics Service Fondazione IRCCS Policlinico San
PATIENTS WITH ADVANCED RECTAL CANCER:
Matteo, Italy; 10University of Palermo, School of RESULTS AND TOXICITY
Radiation Oncology; 11University of Milan, Division of A. Ciabattoni1, F. Salerno1, K.J. Llange1,
Ematology and Emato-oncology, School of Radiation D. di Cristino1, A. Corbosiero1, M.C. Fares1,
Oncology; 12University Federico II of Naples, School of T. Palloni1, A. Siniscalchi1, F. Vidiri1, M. Loponte2 ,
Medicine, Department of Advanced Biomedical L. Marino Cosentino3, S. Mancini3, M.A. Mirri1
Sciences, Italy 1UOC Radioterapia, P.O. San Filippo Neri, ASL Roma

1; 2UOC Chirurgia D’Urgenza, P.O. San Filippo Neri,


Background: PIOPPO is a prospective, phase II,
ASL Roma 1; 3UOC Chirurgia Generale ed Oncologica
multicentre, single-arm study started at CNAO to assess
P. O. San Filippo Neri, ASL Roma 1, Italy
the efficacy and the feasibility of the neoadjuvant admi-
nistration of 3 cycles of FOLFIRINOX followed by a Aims: Preoperative radiotherapy (RT), plus che-
short-course of carbon ion radiotherapy (CIRT) for motherapy (CT) is associated with significant improve-
resectable (Rpc) or borderline resectable pancreatic ment in local control and better tolerance in advanced
adenocarcinoma (BRpc). rectal cancer (RC), compared to postoperative RT.
Aim: Primary endpoint is local progression free sur- Many experiences have been conducted with short
vival and secondary endpoints are overall survival, R0 course RT (25 Gy/5), followed by immediate or delayed
resectability rate and treatment toxicity. surgery. This schedule demonstrated favorable toxicity
Methods: Thirty patients will be enrolled in the profile and comparable efficacy to “long” course radio-
study, the sample size being defined with an expected chemotherapy. Purpose of this analysis is to evaluate
probability of success proportion of success at 24 the clinical outcomes of short-course RT followed by
months of 60% vs 35% (H0: p <= 0.35-H1: p> 0.35). delayed surgery for elderly patients with advanced RC,
Enrolled patients will undergo the scheme FOLFIRI- unfit for long course therapy.
NOX for 3 cycles of FOLFIRINOX followed by CIRT. Methods: From 2009 to 2018, ninety patients with
CTV is defined as GTV with a 5-mm margin and the locally advanced middle-lower RC were treated with
locoregional elective lymph node and neuroplexus short-course RT. Fifty six (31 male and 25 female)

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Oral Communications

underwent to delayed surgery and the others were trea- advanced RC. This analysis showed a considerable
ted with palliative intent. Median age of the surgical down staging of both T and N, with high rates of con-
patients was 77 (r. 65-88). The characteristics of servative surgery. The toxicity was acceptable, with low
patients and tumors are summarized in Table 1. Acute cancer related mortality and low local recurrence rate.
and late toxicities were assessed according to CTCAE
4.03.
CO032
IMPACT OF MUSIC THERAPY INTERVENTION ON
OXIDATIVE STRESS AND DEPRESSION IN BREA-
Table 1. Patients and Tumor characteristics. ST CANCER PATIENTS UNDERGOING POSTOPE-
RATIVE RADIOTHERAPY: A RANDOMIZED STUDY
V. Burgio1, C. Pisani1, L. Deantonio1, S. Farruggio2,
G. Raina2, L. Girardi3, C. Consol3, C. Guerriero3,
Characteristic N (%)

Median Age 77 (range: 65-88) L. Lorenzini3 C. Gramaglia3, E. Ferrara1,


Gender I. Manfredda1, E. Grossini2, P. Zeppegno3,
Female 25 (45) M. Krengli1,4
Male 31 (55) 1Radioterapia Oncologia, AOU Maggiore della Carità;
Tumor distance from anal verge 2Dipartimento di Fisiologia,Università del Piemonte
≤ 5 cm
Orientale; 3SC Psichiatria, AOU Maggiore della
6-10 m
Carità; 4Dipartimento di Medicina Traslazionale,
>10 cm
Università del Piemonte Orientale, Italy
Clinical Stage
cT3 42 (75) Aims: To evaluate the role of psychotherapy inter-
cT4 14 (25) vention with music therapy elements in early stage
cN+ 26 (46.4) (pT1-2 N0-1) breast cancer patients (pts) during post-
cN0 30 (53.6) operative radiotherapy (RT).
Pathological stage Methods: This is a monocentric randomized per-
pT0 1 (1.8) spective study involved Radiotherapy, Psychiatry and
pT1 3 (5.3) Physiology Institute of University Hospital “Maggiore
pT2 22 (39) della Carità” of Novara approved from our ethical com-
pT3 30 (53.9) mittee. Since March 2018, 56 pts, candidates for adju-
cN0 36 (64) vant radiotherapy, were enrolled. Five patients left the
cN1 14 (25) protocol due to poor compliance. Pts were randomized
cN2 6 (11) in two arms: treatment as usual (TAU) or music psy-
chotherapy group (PSY). Forty-nine patients received
hypofractionated RT (40.5 Gy, 2.7 Gy/fx in 3 weeks or
45 Gy, 2.25 Gy/fx plus boost in 4-5 weeks) for pT1-2
and seven received conventional RT (50 Gy 2 Gy/fx in
Results: Clinical and pathological stages are repor- 5 weeks) for in situ carcinoma. PSY group also received
ted in Table 1. The median follow-up was 70 months (r. psychoterapy with music therapy elements that consi-
6-115). A 3D conformal RT was performed in a prone sted in a weekly session conducted by an experienced
position. The clinical target volume (CTV) included the psychiatrist. Music therapy intervention was performed
primary tumor, the mesorectal space and pre-sacral, in small groups of 4-5 pts. At T0 (CT-simulation day),
internal iliac (up to the promontory) and obturator T1 (last RT day) and T2 (3-4 months after the end of
lymph nodes. The time to surgery was in a range of 6- RT) all pts performed blood samples to investigate
22 weeks (mean 8) after RT end. The surgical resection GSH, MDA, TNF-α, IL-6, PCR, phospholipase A2,
was: low anterior in 41 patients (73,2%), abdomino- gamma tocopherol, lycopene levels. Psychometric eva-
perineal in 12 (21,4%) and trans-anal in 2 (5,3%). luation was performed by Beck Depression Inventory,
Adjuvant CT (5-FU or capecitabine-based regimen) Montgomery-Asberg Depression Rating Scale, State-
was administered to 15 patients (26,7%) on the basis of Trait Anxiety Inventory 1-2, Resilience Scale for Adults
pathological stage. T and N histological down staging and Short Form-36 to assess depression, anxiety and
was reported in 35 patients (62,5%) and in 19 of the 38 resilience. Data of the two groups (TAU and PSY) were
cN+ (50%) respectively. One patient achieved patholo- analyzed and compared by t-Student test.
gic complete response. Grade 1-2 acute gastrointestinal Results: Twenty-seven pts were enrolled in the TAU
and genitourinary toxicity were found in 26% and 5.3% and twenty-four pts in the PSY group. At T1, lipidic
respectively. Early and late severe toxicities were not peroxidation markers were significantly reduced in
reported. Thirty four patients (60,7%) are alive without PSY group (p<0.05). At T2, IL-6 levels resulted signifi-
disease, Cancer related mortality and local recurrence cantly lower than T0 in the PSY group, while an increa-
rate were 17,8% and 21,4%, respectively. sing trend at T1 and T2 was observed in TAU group. A
Conclusions: Short-course RT with delayed surgery reduction trend of gamma tocopherol/cholesterol and
in unfit elderly patients may be a valid option in locally lycopene/cholesterol was observed at T2 in both grou-

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

ps. No significant difference of GSH and PCR levels (GR2) and high risk (GR3): to reduce RT dose delive-
was found between two groups. Psychometric tests are red after 4/6 cycles of CT in pts in CR (complete disap-
still under analysis. pearance, or ≥75% reduction of bulky masses, and
Conclusions: Music therapy elements was a feasible metabolic response) or PR (<75% reduction at conven-
and well accepted psycotherapy intervention in early tional imaging).
stage breast cancer pts during postoperative RT. A signi- Methods: GR1, stages I-IIA without M/T >0.33 or
ficant reduction in lipidic peroxidations markers at T1 >4 nodal regions or lung hilar adenopathy; GR2, pts not
and in IL 6 at T2 was observed in the PSY group. included in GR1 and GR3; GR3, stages IIIB-IV or pts
Psychometric data are expected soon to complete the with bulky disease (M/T>0.33). GR1 pts received 3
pts assessment. ABVD and 25,2 Gy only to PR pts after CT. GR2 pts
received 4 COPP/ABV + 14.4 Gy to involved nodal
regions if CR achieved; pts in PR received 2 further
cycles of IEP (Ifosfamide, Etoposide and Prednisone)
CO033
and RT (14,4 Gy if CR, 25.2 if PR). GR3 pts received 4
COPP/ABV and 2 additional COPP/ABV+RT if CR
AIEOP LH-2004 PROTOCOL FOR CHILDREN AND

was achieved; in PR pts, 2 cycles of IEP were admini-


ADOLESCENTS WITH HODGKIN LYMPHOMA:

stered and 14.4 Gy if CR was obtained. If not, pts recei-


RADIATION FREE AND LOW DOSE INFOLVED
ved 2 additional COPP/ABV and RT according to the
FIELD RADIOTHERAPY ARE SUFFICIENT IN COM-
quality of response. The response was evaluated after
PLETE REMISSION LOW AND STANDARD RISK
the 2nd and the 4th cycle and at the end of CT in GR3,
PATIENT
M. Mascarin1, G.Fiumana2, R. Rondelli3, G. Scarzello4, by conventional imaging and with PET in pts with
M. Pillon5, A. Sala6, S. Buffardi7, P. Quarello8, mediastinal mass.
P. Farruggia9, E. Facchini3, A. Mussano8, L. Vinti10, Results: From June 2004 to April 2017, 1115 pts
A. Garaventa11, S.Barra12, P. Muggeo13, M. Provenzi14, were eligible and 948 pts were evaluable for this analy-
F. Porta15, R.M. Mura16, G. Russo17, R. De Santis18, sis (M/F 1,24; median age 13 yrs; range 1,2-17,9) with
F. Casale19, T. Casini20, S.Bernasconi21, K. Perruccio22, a diagnosis by the end of December 2014. The median
R. Pericoli23, M. Cellini24, P. Bertolini25, S. Cesaro26, observation time is 56 months. NS is the most frequent
P. Pierani27, A. Sau28, C. Cosmi29, C. Consarino30, histological subtype (78%); 158 (17%) pts were in
D. Sperlì31, F. Verzegnassi32, E. Coassin1, C. Elia1, GR1, 206 (22%) in GR2 and 584 (61%) in GR3 (41%
M. Zecca33, R. Burnelli2 on behalf of the Italian of them due to bulky disease). The OS, EFS and FFP at
Association of Pediatric Hematology and Oncology 10 years are 93.8%, 76.7% and 80.5% respectively. The
1Centro di Riferimento Oncologico (CRO) IRCCS;
EFS at 10 yrs of GR1, GR2, GR3 are 84.4%, 80.3% and
2Azienda Ospedaliero-Universitaria Sant'Anna; 74.1%. The FFP at 10 yrs is 87.8% for GR1, 88.2% for
3Policlinico Sant’Orsola-Malpighi; 4IOV Istituto
GR2 and 75.4% for GR3. GR1: 69% of pts achieved
Oncologico Veneto; 5Azienda Ospedaliera CR after CT and spared RT, with no statistical differen-
Universitaria; Fondazione MBBM, Ospedale San
6
ce in FFP rates with pts who received RT because in PR
Gerardo; 7Ospedale Santobono-Pausilipon;8Ospedale (87,9% vs 87,8% at 10 yrs). GR2: 75,7% of pts received
Regina Margherita - Sant’Anna;9ARNAS Ospedali 14,4Gy because in CR at the end of CT, without any dif-
Civico Di Cristina e Benfratelli;10IRCCS Ospedale ferences in FFP (88% vs 90% at 10 yrs) compared to pts
Pediatrico Bambino Gesù;11IRCCS Istituto Giannina treated with higher dose of RT because in PR at the end
Gaslini; 12Ospedale Policlinico San Martino;13Az. of CT. In GR3, in PR pts additional CT and RT dose did
Ospedaliero-Universitaria Consorziale not succeed in overcome the gap (FFP 91,6% in CR pts
Policlinico;14Ospedali Riuniti; 15Ospedale dei Bambini vs 74,8% in PR pts at 10 yrs).
degli Spedali Civili; 16Ospedale Pediatrico Conclusions: This HL trial shows that GR1 or GR2
Microcitemico; 17Azienda Policlinico-Vittorio pts in CR after CT may be successfully treated with a
Emanuele; 18Casa Sollievo della RT-free regimen (11%) or with low dose IF-RT (45%)
Sofferenza;19Università degli Studi della Campania respectively. In GR3 pts the additional CT and RT did
Luigi Vanvitelli; 20Azienda Ospedaliero-Universitaria not overcome the gap between CR e PR.
Meyer; 21 Azienda Ospedaliero-Universitaria Pisana;
22Azienda OspedalieraUniversitaria S.M. della
Misericordia; 23Ospedale Infermi; 24Azienda Policlinico
Universitario; 25Azienda Ospedaliero Universitaria;
CO034

26Ospedale Donna Bambino, Azienda Ospedaliera


CARDIAC SUBSTRUCTURES DOSE SPARING IN
Universitaria Integrata; 27Azienda Ospedali Riuniti
PEDIATRIC HODGKIN’S LYMPHOMA
Presidio G. Salesi; 28Ospedale Spirito Santo; 29Azienda I.I. De Cumis, I. Solla, M.A. Deidda,
Ospedaliera Universitaria;30Azienda Ospedaliera R. Farigu, S. Loi, R. Barbara
Pugliese-Ciaccio;31Struttura Ospedaliera Annunziata; Dipartimento di Radioterapia Oncologica, Ospedale
32IRCCS Burlo Garofolo; 33IRCC Policlinico San Oncologico A. Businco AOB, Dipartimento di Fisica
Matteo; Italy Medica, Ospedale Oncologico A. Businco AOB, Italy
Aims: Low risk (GR1): to reduce treatment toxicity Aim: Pediatric Hodgkin’s Lymphoma (HL) survi-
avoiding RT in pts with CR after CT. Standard risk vors represent a group of patients at high risk for clini-

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Oral Communications

cal and subclinical cardiovascular (CV) disease. The of CS contouring.


incidence of CV events increases over time from the Conclusions: Mediastinal radiation dose is the most
diagnosis. Both chemotherapy and radiotherapy (RT) important risk factor for the appearance of late CV
are responsible for cardiotoxicity. Often RT target is disease in pediatric HL. Lower radiation doses for cur-
located near critical cardiac substructures (CS) such as rent protocols and IMRT BT treatment planning increa-
origin of coronary arteries and cardiac valves. Thus, se dose sparing for CS so that further reduction of car-
became important to assess the risk of long-term CV diac late effects may be expected.
complications after therapy. In this study, we analyzed
the dose received by different CS using intensity-modu-
lated radiation therapy (IMRT) “butterfly” technique
CO035
(BT).
Materials: Four pediatric HL (mean age 13) with
ADAPTIVE PROTONTHERAPY FOR PEDIATRIC

stage II-IV and mediastinal bulky disease at diagnosis


PATIENTS WITH HEAD AND NECK PARAMENIN-

were treated with involved-site radiotherapy (IS-RT).


GEAL RHABDOMYOSARCOMA
S. Vennarini1, G. Scarzello2, M. Cianchetti1,
Treatment plans were performed with TPS Pinnacle,
G.M. Milano3, I. Russo3, P.L. Di Paolo4, F. Fellin1,
planning a total dose range from: 14,4Gy in 8 fractions A. Mussano5, M. Amichetti1, S. Lorentini1
for patients enrolled in AIEOP LH 2004 protocol, and 1U.O. Protonterapia, APSS, Trento; 2U.O.C. di
28.8Gy in 16 fractions for patients enrolled in Euronet
PHL C2 protocol. We use Contrast CT (cCT) for seg- Radioterapia Istituto Oncologico Veneto, Padova;
3Dipartimento di Onco-Ematologia e Medicina
mentation of CS, than we performed deformable image
registration (DIR) in MIM Software to adapt organs at Trasfusionale, Ospedale Bambino Gesù (O.P.B.G.),
risk between cCT and Simulation CT. The following CS Roma; 4Dipartimento di Radiologia, Ospedale Bambino
were contoured: right and left atrium, right and left ven- Gesù (O.P.B.G.) Roma; 5AOU, U.O. Radioterapia, Città
tricle, aortic, pulmonary, mitral and tricuspid valves, della Salute e della Scienza, Torino, Italy
left main, left anterior descending, left circumflex and Introduction: Protontherapy (PT) is an established
right coronary arteries. IMRT plans were generated treatment for pediatric malignancies because of the
using 5 co-planar beams (3 anterior 330°- 0°- 30° and 2 optimal target coverage and surrounding normal tissue
posterior 160°-210°) BT. We analyzed PTV coverage sparing that can be achieved. This advantage can be lost
(mean dose -Dmean- and V95% -percentage volume if anatomical target changes occur, leading to alteration
receiving 95% of prescription dose-), and doses to CS of the initial dose distribution. Our purpose was to
(Dmax, Dmean). monitor with scheduled re-planning Ct scans, initial
plan dose alterations in selected complex pediatric
malignancies such as parameningeal head and neck
(H&N) rhabdomyosarcoma (PM-RMS).
Material and methods: At the Trento Protontherapy
Table 1 and Figure 1.

Center, from February 2018 to April 2019, 6 patients (pts)


(3 male, 3 female) affected by H&N PM-RMS ( 3
embryonal, 3 alveolar) were studied. Median age was 9
years (range: 4-16); 2 pts had localized disease, 4 had
neck lymph nodes metastases. Three pts required general
anesthesia. PT was definitive for all of them. Staging was
IRS III N1 for 4 pts and IRS III N0 for 2. Chemotherapy
was administered according to the EPSSG 2005 protocol.
PT dose to the low risk clinical target volume (CTV) was
50.4 Gy(RBE) delivered in 28 fractions of 1.8 Gy(RBE),
followed by a boost of 5.4 Gy(RBE) in three fractions of
1.8 Gy(RBE) to the high risk CTV. Neck CTV mean dose
was 43.6 Gy(RBE) (range: 41.4-50.4). Treatment plan
was multifield optimization (MFO) for low risk CTV and
single field optimization (SFO)for high risk CTV and
neck CTV. Pts were monitored with a CT-on-rail sited in
the treatment room. The nominal treatment plan was
recalculated on the re-planning CT and if significant
variations were found it was optimized again. The deci-
sion to re-optimize was taken in a case-by-case scenario
Results: Dose sparing of CS, especially origin of considering dosimetric and clinical parameters. Pts were
coronary arteries and cardiac valves, is achievable with re-scanned regularly once a week for the first three weeks
IMRT BT. In in case of overlap with target, priority is than accordingly to the clinical situation and to the fin-
assigned to target coverage. We met following PTV dings of the re-calculation.
coverage: V95%= 97±2% and Dmean =19Gy. Dose for Results: All pts completed their treatment as sche-
CS are reported in table. Image represents an example duled without unplanned breaks due to side effects. The

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

total number of re-planning CT was 27, mean number prescribed doses were 54 Gy for CNS tumors, 25.2 Gy
for pt was 4 (range: 3-6). Two out of 6 ps had their plan for lymphomas, 50.4 Gy for sarcomas, 66 Gy for H&N
optimized again 2 times each. Reason for re-optimiza- cancers, and 15-21 Gy for the remaining cases. The
tion was paranasal sinuses mucous filling; in one case cumulative incidence of SMN and radiation-induced
important weight loss contributed as well. benign tumors was 1% (1/87) and 2% (2/87), respecti-
Conclusions: Our study demonstrate the feasibility vely. At a median follow-up of 7.6 yrs (5.2-12.7), 68
and safety of prototherapy for pediatric H&N PM-RMS patients (78%) were alive in complete remission.
and the need for plan robustness close evaluation. Among these long-term survivors, a 13-y-o patient
developed a secondary fifth cranial nerve schwannoma
12 yrs after HT for recurrent supratentorial ependymo-
ma (Figure 1). A 17.5-y-o female affected by Hodgkin
CO036
lymphoma developed a recurrent fibromatosis of the
soft tissues of the breast region close to the central
INCIDENCE OF SECOND MALIGNANCIES AMONG

venous catheter insertion site within the irradiated area


PEDIATRIC PATIENTS TREATED WITH HELICAL

5 yrs after HT (14.4Gy/8fr). At a median follow-up of


TOMOTHERAPY
E. Coassin, A. Drigo, L. Barresi, C. Elia, G. Sartor,
7.2 yrs (5-8.9), 10 patients (12%) were died of disease.
G. Franchin, M. Mascarin
One patient died because of esophageal cancer 7 yrs
Centro di Riferimento Oncologico di Aviano (CRO) after total pleural irradiation for Ewing sarcoma of the
IRCCS, Italy thoracic wall (36Gy/20fr). The tumor arose within the
Aims: IMRT delivered with helical Tomotherapy high-dose volume. Nine patients (14%) were alive with
(HT) has been increasingly applied in young patients disease without evidence of SMN at the time of the
with cancer. Concerns about a potential increase of study.
radiation-induced malignancies (SMN) exist. The aim Conclusions: This is the first report of SMN risk in
of this study was to determine the incidence of SMN children undergoing HT. With a follow-up of up to 12
among pediatric patients treated with HT. yrs, HT resulted not associated with an increased risk of
Methods: We analyzed the incidence of SMN SMN due to low-doses to normal tissues as previously
among 153 patients less than 24 yrs of age treated with reported. Longer follow-up is required to determine
HT since its introduction in 2006 to May 2014 at our how this risk compares to other IMRT techniques and
Institution. proton therapy.

CO037
PITUITARY DEFICITS AFTER RADIOTHERAPY IN
PEDIATRIC PATIENTS AFTER LONG TERM FOL-
LOW-UP
E. Tornari1, C. Satragno1, A. Pastorino1, S. Barra2,
F. Giannelli2, M. Giaccardi3, L. Belgioia1,2,
M.L. Garrè4, M. Crocco3, R. Haupt5, N. Di Iorgi3,
R. Corvò1,2
1Dipartimento di scienze della salute (DISSAL)

Università degli studi di Genova; 2Radioterapia


Oncologica Ospedale Policlinico San Martino Genova;
3Dipartimento di Pediatria Istituto Giannina Gaslini

Università degli studi di Genova; 4Dipartimento di


Figure 1.
Neuro-oncologia Istituto Giannina Gaslini Genova;
5Epidemiologia e statistica Istituto Giannina Gaslini

Genova, Italy
Aims: To evaluate the risk of developing pituitary
deficits in pediatric patients (pts) with CNS tumors trea-
Results: Eighty-seven patients with a follow-up of ted with radiotherapy
at least 5 yrs after HT were included. The median fol- Methods: We retrospectively analyzed patients with
low-up was 7.6 yrs (5-12.7). The median age at HT was brain tumors, younger than 16 years, treated between
14 yrs (1.5-24). Patients were irradiated with HT alone 1996-2015 with a minimum follow up of 2 years after
or in combination with other radiation techniques for the end of radiotherapy. In this study, we evaluated
CNS tumors (n=39), lymphomas (n=23), sarcomas three deficits: GH deficiency (GHD), ACTHD and
(n=17), H&N cancers (n=5), or other histologies (n=3). TSHD. We registered the dose to the target and the
Treatment sites were brain (n=25, 2 whole ventricular), mean dose to the organs at risk (OARs) analyzing the
mediastinum (n=22), craniospinal (n=14), H&N (n=7), results related to hypothalamus and pituitary gland.
pelvis (n=6), thorax (n=5, 2 total pleural), limbs (n=4), Cumulative dosage for medulloblastoma, germinoma,
abdomen (n=3, 1 whole abdomen), spine (n=1). Median glioma and ependymoma was calculated by the sum of

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Oral Communications

the cranio-spinal dosage and the dose received from the lung, compression of the heart, ptosi of liver and right
boost. The population was divided into four (4) groups kidney and two subpleural micronodules on the left. He
depending on the dose of radiotherapy given: Group 1: underwent a thoracotomy and biopsy that showed PPB
0-14 Gy, Group 2: 15-29 Gy, Group 3: 30-39 Gy and type III. The patient received chemotherapy according
Group 4: ≥40 Gy. to the EpSSG-RMS high risk protocol (with ifosfamide,
Results: 88 patients have been identified: 20 pts vincristine, actinomycin, doxorubicine –IVaDo-for
were excluded because they presented hormone defi- three cycles). Restaging chest CT showed a residual
ciency before starting radiotherapy, and 4 pts because right disease and disappearance of the two micronodu-
they had an endocrinological follow-up of lower than 2 les.He underwent second gross total resection of the
years. Therefore, 64 patients were evaluated: 32 medul- superior and medium lobe of the right lung and biopsy
loblastomas (50.0%), 17 gliomas (26.5%), 7 germino- of the supraclavear pleura. Histological study confir-
mas (10.9%), 3 ependymomas (4.6%), and 5 other med residual PPB on the pleural tissue and necrosis on
histological types (7 8%) (2 Ewing sarcomas, 1 PNET, the lung. He received adjuvant chemotherapy ( for five
1 pinealoblastoma, 1 AT/RT). 61 pts also underwent to cycles with regimen IVA-ifosfamide, vincristine, acti-
chemotherapy and 42 to surgery. The mean pituitary nomycin D) that was well tolerated with no dose reduc-
dose in patients with GHD was 36.5±9.78 Gy (p 0.01), tion. Restaging TC didn’t show residual disease.
TSHD 38.0±6.0 Gy, ACTHD 34.6±10.5 Gy. Patients The colleagues of hospital Bambin Gesù contacted
treated with 3DRT had a higher risk of developing U.O. Radioterapia Oncologica Ospedale Policlinico
GHD, ACTHD, and TSHD if compare with IMRT tech- San Martino of Genova to ask a comparison between
niques (p<0,05).The "safe dose" under which no patient their VMAT treatment plan and a plan elaborated with
has shown GH deficiency is <10 Gy while for TSH and tomotherapy Hi-Art tecnology. The last one showed
ACTH deficit is <20 Gy. best results in term of target coverage and of organ at
Conclusions: The data of our study underline the
risk saving . So we decided together to treat the patient
role of the dose delivered to the pituitary in the different
with tomotherapy. He received radiotherapy to the pleu-
radiotherapy techniques in the development of neuroen-
ral cavity of the right hemythorax with 50,40 Gy in 28
docrine late toxicity.
Fractions (1,8 Gy/fx) with IMRT-IGRT technique using
Tomotherapy Hi-art system in helical modality (treat-
ment of 45 days). Plan was delivered in 650 seconds
and the patient was under anesthesia. Tomotherapy plan
CO038

was created with Field width 1,05, fixed and Pitch


RADIOTHERAPY IN A PLEURO-PULMONARY BLA-
0,287. The volume of PTV was 320 cc. The 95% of
STOMA OCCURING IN A 2-YEAR OLD MALE:
A CLINICAL CASE REPORT PTV is covered by 92% of dose.The difference between
N. Luca1, C. Satragno2, D.Tramontano2, A. Pastorino2, right lung and the PTV has an average dose of 35 Gy.
E. Tornari2, M.D. De Pasquale3, F. Cavagnetto4, To decrease left lung dose the “directional block” was
F. Giannelli5, S. Barra5, R. Corvò2,5 applied.
1Università degli studi di Palermo-ARNAS Civico; Results: Radiotherapy was well tolerated: he only
2Università degli studi di Genova DISSAL; had G1 erythema according to RTOG tox. Last brain
3Oncoematologia Ospedale Bambin Gesù IRCCS
and chest TC didn’t show recurrence of disease. The
Roma; 4Ospedale Policlinico San Martino Genova, patient today is alive in complete remission (10 months
UOC Fisica Medica; 5Ospedale Policlinico San after radiotherapy) and he is in maintenance chemothe-
Martino Genova, U.O.S. Radioterapia infantile e tecni- rapy. He didn't develop late side effects; he has a good
che speciali-Università degli studi di Genova, Italy respiratory function.
Aims: Pleuro-pulmonary blastoma (PPB) is a mali- Conclusions: PPB is a rare and aggressive mali-
gnancy of the lungs that accounts for 0,5% of all pedia- gnant tumor that arises from mesenchymal cells of the
tric malignancies. It occurs in children less than 6 years lung. The treatment is multimodal and includes surgery,
of age. PPB is classified into three main types: type I is chemotherapy and radiation therapy. In PPB the volu-
cystic, type II is mixed cystic and solid, and type III is mes that must be irradiated are large: with the help of
solid and aggressive sarcoma. Tipe I has the best pro- the new technologies (such as the tomotherapy) we can
gnosis; type II and III have a 5-years survival rate of treat the patients even if they are young.
53% , because of frequent relapse and distant metasta-
ses (brain, bone, liver, pancreas, kidney and adrenal
gland). The patients with PPB usually develop respira-
tory symptoms: dyspnea, chest pain, cough, respiratory
distress, pneumotorax, fever, persistent pneumonitis, ,
atelectasis.
Materials and Methods: A 2 year old male was
admitted to the hospital Pediatrico Bambin Gesù
(Rome) because of a hemorrhagic shock due to rupture
of a right pulmonary mass. A chest computed tomo-
graphy (CT) scan revelead a solid mass in the right

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9.5 mm at the distal tract) Table 1.


Results: Radiation therapy was well tolerated, with
CO039

no evidence of acute toxicity.


Conclusions: This is a very rare localization of the
IMPLEMENTATION OF A METHOD FOR HEART

Ewing’s Sarcoma, but with the use of specific Heart CT


IRRADIATION: A CASE REPORT OF INTERATRIAL

could be possible give Radiation therapy to a moving


EWING’S SARCOMA
A. Pastorino1, C. Satragno1, E. Tornari1, N. Luca2,
S. Barra3, F. Giannelli3, S. Seitun4, C. Manzitti5, organ.
A. Garaventa5, S. Garelli6, R. Corvò1,7
1Dipartimento di Scienze della Salute (DISSAL)

Università degli Studi di Genova; 2Università degli


Table 1.
Studi di Palermo – Arnas civico; 3Ospedale Policlinico
San Martino Genova, U.O.S. Radioterapia infantile e
tecniche speciali; 4Ospedale Policlinico San Martino
Genova, U.O. Radiologia Interventistica; 5Istituto
Giannina Gaslini, U.O.C. Oncologia; 6Ospedale
Policlinico San Martino Genova,U.O.C. Fisica Medica;
7Ospedale Policlinico San Martino Genova, U.O.C.

Oncologia Radioterapica, Italy


Aims: Primitive neuroectodermal tumor and
Ewing’s Sarcoma of cardiac origin are rare entities
among primary cardiac neoplasm.Ewing’s Sarcoma
occurs between the ages of 5 and 30. The tumor initially
develops most frequently in bone, particularly in the
pelvis.The disease has a high potential for metastases.
Methods: A 9 years old child went to the hospital for
orsening asthenia, loss of appetite and low-grade fever
in May 2018.A chest X-ray showed a significant increa-
CO040
se in cardiac shadow associated with severe pleuric and
pericardial effusion, with a “Swimming Heart” situa-
USE OF AUTOMATIC FEATHERING ALGORITHM

tion. The histological examination, performed at the


(ECLIPSE V.15) IN THE VOLUMETRIC-

Giannina Gaslini Institute in Genoa, of cardio-surgery


MODULATED ARC THERAPY (VMAT)

in extra-corporeal circulation with the implant of pace-


PLANNING OPTIMIZATION FOR CRANIOSPINAL

maker, showed the presence of a Sarcoma of the


IRRADIATION
G. Benecchi1, M. Maddalo1, C. Di Carlo2, C. Ghetti1,
Ewing/PNET family, with negativity for neoplastic cell P. Losardo2, R. Rossi1, C. Grondelli2, E. Calabri1,
research in pleural and pericardial effusions. The child F. Salaroli2, M. Manicone2, S. Gianni2, E. Lattanzi2,
was initiated into the EW1 protocol (modified arm A). N. D’Abbiero2
After chemotherapy, the child was given Radiotherapy 1Medical Physics Department of Parma Hospital;
at our Ospedale Policlinico San Martino. On the same 2Radiation Oncology Department of Parma Hospital,
day she underwent CT-scan with personalized thoracic-
abdominal immobilization system (Orfit) and heart CT Italy
at Radiology at our Institute, with images fusion in Aim: Craniospinal irradiation (CSI) is often the
order to plan treatment with maximum accuracy and treatment of choice for pediatric tumors like medullo-
minimise cardiac toxicity.The exam was done with CT blastoma or leukemia and lymphoma affecting the cen-
Definition Flash (128x2 layers) before and after rapid tral nervous system (CNS). However, matching the cra-
somministration iodinate contrast agent, with perfor- nial and spinal fields requires careful technical planning
med on a Dual-Flash perspective spiral technique in taking into account intra-fraction patient position inac-
diastole and systole and subsequent retrospective acqui- curacies that may cause cold and/or hot spots where the
sition with perspective beam modulation and recon- treatment fields overlap. The aim of this study is to
structions in multiple phases of the RR range (0-100%) compare the sensitivity of VMAT cranio-spinal techni-
with an average heart rate of 93bpm. After collegial que to set-up errors between Eclipse v.13 and Eclipse
discussion we decide to give the child radiotherapy of v.15 with its new Automatic Feathering (AF) algorithm
the interatrial septum, evaluating during and after each for craniospinal treatment planning.
session the heart rate. The child received 59.40 Gy in 33 Methods: AF algorithm was retrospective tested on
fractions, 5 times/week with daily IMRT-IGRT techni- two pediatric patients (1 medulloblastoma e 1 acute
que using Tomotherapy, from 08/04/2019 to 30/05/2019 lymphatic leukemia affecting CNS) treated in our
due to residual lesion after unradical surgery and Institute, in supine position, with standard VMAT tech-
Chemiotherapy.The PTV was defined with the Heart- nique using Eclipse v.13. Both treatments had 3 isocen-
CT considering the excursion of the right coronary., ters (1 cranial and 2 spinal) and 2 junctions of 5 cm.
(systo-diastolic movement 7.5 mm in the longitudinal Each plan was re-optimized using Eclipse v.15 with AF
axis at the proximal tract, 9 mm at the medium tract and algorithm. The sensitivity of AF feature was evaluated

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Oral Communications

by shifting the isocenters of the brain plan closer


towards the second isocenter by 1mm, 3mm and 5 mm
CO041

simulating different set-up errors. The impact of AF


algorithm was then evaluated by comparing maximum
THE FAST APPROACH AS ADJUVANT WHOLE

doses at fields junction. In order to asses field junction


BREAST IRRADIATION FOR FRAIL BREAST

dose more accurately, single and total field dose profiles


CANCER PATIENTS
M.A. Zerella1,4, S. Arculeo1,4, A. Casbarra1,4,
in CC direction were also compared for each simulated S. Dicuonzo1, V. Dell’Acqua1, M.A. Gerardi1,
set-up error. A. Morra1, C. Fodor1, F. Cattani2, V. Galimberti3,
Results: For both patients we compared average P. Veronesi3,4, R. Orecchia5, M.C. Leonardi1,
maximum doses of Eclipse v.13 and Eclipse v.15 for B.A. Jereczek-Fossa1,4
different simulated setup errors (shifts) at the field junc- 1Division of Radiation Oncology, European Institute of
tion. Respect to Eclipse v.13, Eclipse v.15 with AF Oncology, IEO IRCCS, Milan; 2Unit of Medical
algorithm reduced the average maximum dose for 3 mm Physics, European Institute of Oncology,IEO IRCCS,
shift of about 14% and for 5 mm shift of 22%. Figure 1 Milan; 3Division of Breast Surgery, European Institute
shows the dose profiles across the junction as a function of Oncology ,IEO IRCCS, Milan; 4Department of
of the different shifts for the most representative Oncology and Hemato-oncology, University of Milan,
patient. Eclipse v.13 yields in an high and sharp peak Milan; 5Scientific Direction, European Institute of
that falls outside of the junction, while Eclipse v.15 Oncology, IEO IRCCS, Milan, Italy
yields in a slight increase that spreads over the entire
junction. Aim: To evaluate the outcome in terms of toxicity,
Conclusions: This study proved that AF algorithm local control and survival of elderly breast cancer (BC)
is able to effectively optimize the dose distribution patients treated with adjuvant once-weekly hypofractio-
where the treatment fields overlap avoiding cold and nated radiotherapy (RT).
hot spots due to intra-fraction setup errors. Future deve- Methods and Materials: From 7/2011 to 7/2018,
lopments of this study will concern about the possibility 271 BC patients were given received 5.7 Gy once a
of further reducing hot and cold spots due to setup week for 5 weeks to the whole breast, without boost to
errors considering different junction extensions and a the tumor bed (total dose 28.5 Gy), after breast conser-
greater number of patients. ving surgery. Patients were eligible if affected by T1-T3
invasive BC, with no or limited axillary involvement.
The scheme was offered to elderly women (age thre-
shold of 65 years) and to those with commuting diffi-
culties or disabling diseases.

Table 1. Disease free survival for all the patients.

Results: Median age was 76 (45.5-86.4) years.


Median follow-up was 24.6 (6.2-65.7) months. Most of
BC were T1 (77%), while the remaining were T2
(22.2%), T3 (0.4%). Axillary status was negative in
68.3%, minimally involved in 14.4% (pN1) and not
Figure 1.

assessed in 17.3% of the cases (Nx). Most of the

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

women received hormonal therapy (84%), while 10.7% Methods: From June 2009 to December 2017, 734
received chemotherapy. The schedule was delivered ER-positive BC pts (stage pT1-T2, pNx-1, M0 and age
either with three-dimensional conformal RT (n=133) or over 65 years) receiving Hypo-RT and followed until
with intensity modulated RT (n=138). No statistically September 2018, were analyzed. Hypo-RT consisted of
significant difference was observed between the two 42.4 Gy in 16 daily fractions, a sequential boost was
techniques in terms of toxicity and efficacy. Maximum administered in cases of grade 3 tumor and close or
acute toxicity at the end of RT for 271 patients was as positive margins. Baseline comorbidities included in
follows: grade (G) 1, 2 and 3 erythema in 63%, 7% and the hypertension-augmented Charlson Comorbidity
0.4% of patients, respectively. G2 edema was detected Index (hCCI) were retrospectively retrieved. Baseline
in 10% of patients. Desquamation occurred in 4.4% as pts and tumour characteristics were analyzed in relation
G1 and 1.5% as G2 of cases. At median 2-year follow to HT status (never/discontinued, ongoing) at last con-
up, LENT-SOMA assessment was available for 137 tact by chi-2 test. Five-year disease-free survival (DFS)
patients. Fibrosis (G1 and G2 in 46.7% and 9.5%, and overall survival (OS) were estimated by Kaplan-
respectively) and skin changes (G1 and G2 hyper- or Meier method. The log-rank test was used to compare
hypo-pigmentation in 29.2% and 2.2% respectively, G1 groups. Adjusted hazard ratios (HRs) were estimated by
and G2 telangiectasia in 3 patients) were observed. A Cox proportional hazards models. In survival analysis,
minority complained pain of G1 (n=26) and G2 (n=2) HT use was treated as time-dependent variable. A sub-
intensity. Two-year oncologic outcome was assessed for group analysis was performed on pts aged ≥70 with a
257 patients. At the last follow-up examination, pT1 luminal A BC.
244/257 patients were alive and free from any event Results: The comorbidity was present in about 70%
(Table 1). There was a total of 5 (1.9%) isolated locore- of pts (median age: 74 years).HT has been prescribed in
gional recurrences: 4 involved the breast and 1 the axil- 88.9% pts. Most of them assumed the prescribed HT and
lary lymph nodes. At 3 years, disease-free survival and 7.8% discontinued the treatment. Current HT use was
overall survival were 100% and 99%. Predictive factors less frequent for pts aged ≥80 (p<0.001) and pts with
for toxicity were breast volume >500 cm3 for acute high comorbidity burden (hCCI≥2) (p=0.001). At the
toxicity, while none was correlated with severe late time of the analysis, 91.7% pts were still alive and 4.5%
toxicity. pts experienced a disease progression (local or nodal
Conclusions: Toxicity was mild and acceptable with recurrences and metastases). At a median follow-up 46.8
high patients’ satisfaction. Local control was accepta- months (range 4-115 months), the overall 5-year DFS
ble, none died of BC and overall survival was 99% at 3 was 86.8% varying between 89.5% for current HT use
years. and 76.6% for no/discontinued HT use ( p<0.001). The
prognostic effect of HT was confirmed for pts aged≥70
with a pT1 luminal A BC: 5-year DFS were 91.3% and
79% for ongoing HT user and no/discontinued HT user,
CO042
respectively ( p<0.018). The hazard of disease progres-
sion was significantly increased for pts with hCCI≥2 and
OLDER AGE AND COMORBIDITY IN BREAST CAN-

with tumour size ≥1 cm and strongly decreased for cur-


CER: IS RADIOTHERAPY ALONE THE NEW THE-

rently ongoing HT users. HT did not impact on OS in


RAPEUTIC FRONTIER?
E. La Rocca1,2, M. Dispinzieri1,2, E. Meneghini3,
A. Fiorentino4, F. Bonfantini5, S. Di Cosimo6, any of the analyzed groups.
M. Gennaro7, V. Cosentino5, M. Sant3, E. Pignoli5, Conclusions: This study shows that disease progres-
R. Valdagni1,8, L. Lozza2, M.C. De Santis2 sion was strongly increased for pts with hCCI≥2 and
1University of Milan, Department of Oncology and tumor size>1 cm and decreased for HT users. In elderly
pts, HT assumption did not showed a benefit in terms of
Hemato-Oncology; 2Fondazione IRCCS Istituto survival. Further studies (RT alone versus RT+HT ver-
Nazionale dei Tumori, Radiotherapy Unit 1; sus HT alone) are needed on elderly women with BC.
3Fondazione IRCCS Istituto Nazionale dei Tumori,

Analytical Epidemiology and Health Impact Unit;


4Regional General Hospital F Miulli, Department of

Radiation Oncology; 5Fondazione IRCCS Istituto


CO043

Nazionale dei Tumori, Medical Physics Unit; PROMOTER METHYLATION OF MGMT ASSOCIA-
6Fondazione IRCCS Istituto Nazionale dei Tumori, TED WITH NEGATIVE EXPRESSION OF
Department of Applied Research and Technological
Development DRAST; 7Fondazione IRCCS Istituto
EPIDERMAL GROWTH FACTOR RECEPTOR

Nazionale dei Tumori, Breast Surgery Unit;


SELECTED A SUB-GROUPS OF LONG SURVIVAL

8Fondazione IRCCS Istituto Nazionale dei Tumori,


GLIOBLASTOMA PATIENTS CANDIDATE TO A DE-

Director- Radiation Oncology 1 and Prostate Cancer


INTESIFICATION OF RADIOTHERAPY TREATMENT
G. Battaglia1, P. Pastina1, V. Nardone 2, G. Rubino1,
Program, Italy T. Carfagno1, M. Vannini1, M. Crociani1, L. Sebaste1,
Aims: To assess the impact of age, comorbidities L. Pirtoli3,4, P. Tini1
and hormonotherapy (HT) use in elderly breast cancer 1Unit of Radiation Oncology, University Hospital of

(BC) patients (pts) treated with hypofractionated Siena, Italy; 2Unit of Radiation Oncology, Ospedale del
radiotherapy (Hypo-RT). Mare, Naples, Italy; 3Sbarro Health Research

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Oral Communications

Organization, Temple University, Philadelphia, PA, Dipartimento di Medicina Specialistica Diagnostica e


USA; 4Department of Biology, College of Science and Sperimentale- DIMES, Azienda Ospedaliera-
Technology, Temple University, Philadelphia, PA, USA Universitaria S.Orsola-Malpighi; 4Fondazione

Giovanni Paolo II, UO di Radiologia, Università


Aim: To explore therapeutic results of de-escalated
radiotherapy (RT) dose schedules combined to Cattolica del Sacro Cuore; 5Fondazione Giovanni
Temozolomide (TMZ)-RT treatment in sub-group of Paolo II, UO di Oncologia Medica, Università Cattolica
patients with very favourable prognosis based on del Sacro Cuore; 6Fondazione Policlinico Universitario
MGMT and EGFR expression in newly diagnosed glio- A. Gemelli, IRCCS, UOC di Radioterapia, Dipartimento
blastoma (GB). di Scienze Radiologiche, Radioterapiche ed
Methods: Patients with newly diagnosed GB recei- Ematologiche, Italy
ved either standard (SDRT: 60-59.4 Gy) or reduced Aims: To assess the feasibility and safety of a repea-
(RDRT: 54-52 Gy) dose radiation therapy (RT) with ted SHort-course Accelerated RadiatiON therapy
concomitant and adjuvant TMZ between June 2010 and (SHARON) regimen in the palliative setting of H&N
October 2016. We retrospectively evaluated the thera- locally advanced or metastatic cancer in elderly
peutic effectiveness of the RT ranges schedules in terms patients.
of overall survival (OS) with univariate and multivaria- Methods: Patients with histological confirmed
te analysis, after analyzing the MGMT methylation sta- H&N cancers, age ≥80 years, expected survival >3
tus and EGFR protein expression.
months and Eastern Cooperative Oncology Group
Results: One hundred patients were selected for the
(ECOG) performance status of ≤3 entered the study.
present analysis. Clustering survival analysis for the
Patients were treated in cohorts of six patients: a total
methylation status of MGMT (methMGMT/
unmethMGMT) and EGFR expression (High EGFR: dose of 20 Gy was delivered in 2 consecutive days with
H-EGFR; Low EGFR: L-EGFR), identified three diffe- a twice daily fractionation (5 Gy per fraction) and at
rent prognostic groups(p = 0.001), as follows. Patients least 6-8 hour interval. If no Grade 3 toxicity was regi-
with unmethMGMT/H-EGFR had the shortest survival stered within 3 months from treatment, a second enrol-
time (median OS: 5months) and patients co-expressing lment started with another cohort of six patients to
methMGMT/L-EGFR had a very long prognosis whom were administered two cycles for a total dose of
(median OS: 35 months),as compared to the other two 40 Gy, with an interval between cycles of about one
sub-groups (methMGMT/H-EGFR; unmethMGMT/L- month. Primary endpoint was to evaluate feasibility of
EGFR), which had respectively median OS of 11 and two cycles. Secondary endpoint was to assess symp-
12 months. Twenty-seven patients were methMGMT/ toms-free progression time and survival.
L-EGFR in which 17 patients received the standard RT- Results: Nineteen consecutive patients (male/fema-
TMZ course (SDRT-TMZ) whereas the remaining ten le: 11/8; median age: 84 years; range: 80-97) were trea-
underwent the reduced dose schedule (RDRT-TMZ). ted. ECOG performance status was 3 in 9 patients
The survival analysis showed that in this sub-group of (48%). Primaries different cancer were included: oral
patients, SDRT-TMZ and RDRT-TMZ groups did not cavity (N°=4; 21%), larynx (N°=4; 21%), oropharynx
show different median OS (p=ns). Instead, a difference (N°=4; 21%), paranasal sinus (N°=3; 16%), lip (N°=2;
in survival outcomes was confirmed in all others 11%), salivary gland (N°=1; 5%), nasal cavity (N°=1;
MGMT-EGFR expressed patients with better survival 5%). Eleven patients were treated with one cycle. No
for patients undergoing to SDRT, experience of Grade 3 toxicity was registered: only one
Conclusions: In our experience, a reduction of patient (10%) reported a pharyngeal G2 toxicity. The
radiation dose schedule should be investigated in this dose was then escalated to 40 Gy and other 8 patients
subgroup of patients and could deserve prospective were treated: three G2 toxicity (38%) were reported
trials for validation. (one pharyngeal, one mucosal and one skin G2 toxi-
city). No G3 toxicity was reported. With a median fol-
low-up time of 3 months, the symptoms free progres-
sion-time in the first group was 3,8 months, whilst in
CO044
PALLIATION OF ADVANCED HEAD AND NECK second cohort was 8 months (Figure 1). The median
(H&N) CANCER IN ELDERLY PATIENTS: A overall survival time was 8 months. Overall palliative
response rate was 99%. Moreover, among 13 sympto-
matic patients for pain, 8 showed an improvement or
REPEATED SHORT-COURSE ACCELERATED

resolution with an overall pain response rate of 62%.


RADIATION THERAPY (SHARON) REGIMEN
M. Ferro1, M. Boccardi1, A. Ianiro2, G. Macchia1,
A. Re1, V. Picardi1, C. Romano2, A. Zamagni3, Conclusions: Repeated short-course accelerated
M. Ferioli3, A. Arcelli3, S. Cammelli3, M. Ferro1, radiotherapy in palliative setting of Head & Neck can-
M. Missere4, S. Mignogna5, M. Buwenge3, C. Pozzo5, cers is safe and well tolerated even in elderly patients.
S. Cilla2, V. Valentini6, A.G. Morganti3, F. Deodato1 A phase II clinical trial will be necessary to verify
1Fondazione Giovanni Paolo II, UO di Radioterapia, whether an increase in the number of cycles can safely
Università Cattolica del Sacro Cuore; 2Fondazione prolong the symptom-free progression time.
Giovanni Paolo II, UO di Fisica Sanitaria, Università
Cattolica del Sacro Cuore; 3U.O. di Radioterapia –

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CO045 CO046
UNCONVENTIONAL RADIOTHERAPY SBRT-PATHY SBRT WITH SIMULTANEOUS INTEGRATED BOOST
VS. STANDARD OF CARE FOR INOPERABLE AND PROTECTION: INCIDENCE AND PATTERN
BULKY LUNG CANCER OF RECURRENCE IN BORDERLINE RESECTABLE
S. Tubin AND LOCALLY ADVANCED PANCREATIC CANCER
KABEG Klinikum Klagenfurt, Institut für N. Simoni1, R. Micera1, G. Rossi1, S. Guariglia2,
Radioonkologie, Austria N.L.V. Cernusco1, M. De Liguoro1, A. Muraglia1,
M. Romano 1, M.G. Giri2, E. Zivelonghi2,
Aim: to report on the improved therapeutic ratio by C. Cavedon2, R. Mazzarotto1
newly developed SBRT exploiting the bystander (BE) 1Department of Radiation Oncology, 2Medical Physics
and abscopal effects (AE) for the treatment of either
Unit, University of Verona Hospital Trust, Italy
inoperable or unsuitable for radical radiotherapy bulky
lung cancer compared with standard of care. In a pre- Aims: To analyze incidence and pattern of recurrence
clinical phase of this translational research was proven and to define a dosimetric map of loco-regional failure
that the hypoxic tumor cells show higher potential for (LRF) after Stereotactic Body Radiation Therapy
tumoricidal BE and AE compared with normoxic tumor (SBRT) with Simultaneous Integrated Boost (SIB) and
cells. In order to improve the radiotherapy outcome by Protection (SIP) for pancreatic cancer (PC) patients (pts).
generating BE and AE those findings were translated to Methods: We retrospectively reviewed 51 consecu-
the clinic, and new SBRT-based PArtial Tumor irradia- tive pts (26 borderline resectable and 25 locally advan-
tion targeting HYpoxic segment (SBRT-PATHY) but ced disease) treated from November 2016 to August
sparing tumor immune-microenvironment was develo- 2018. All the pts received induction chemotherapy prior
ped. The hypothesis is that SBRT-PATHY can improve to SBRT. SBRT was delivered over 5 consecutive frac-
the local and distant tumor control inducing major tions using a SIB technique, prescribing 10 Gy/fraction
regression of partially irradiated bulky due to BE but to the region of vessel abutment/encasement and 6
also of unirradiated metastases due to AE. The primary Gy/fraction to the remaining Planning Target Volume
endpoint was bulky response rate. The secondary end- (PTV) tumor. SIP was generated prescribing 25 Gy on
points included: distant tumor control, survival, safety, the overlap area between the PTV and the Planning
symptom control. Organ at Risk Volume. Elective Nodal Irradiation (ENI)
Materials and Methods: 60 patients stage IIIB/IV was not performed. 27 pts underwent surgical tumor
bulky lung cancer considered inoperable or unsuitable resection after SBRT. For the analysis we defined 3 dif-
for radical radiotherapy were treated (Aug. 2013 - Aug. ferent site of failure: in field (inside the isodose 30 Gy),
2018) with: 1. Conventional RT only: 3Gy x 10 to the out field (area corresponding to the ENI) and distant
bulky (20 patients), 2. Standard CHT only (20 patients), failure. We realized for each location of LRF a dosime-
3. SBRT-PATHY only: 10 or 12Gy x 1-3 to 70% (based tric evaluation matching the computed tomography
on bulky site and volume) to a so called Bystander (CT) that showed LRF with the SBRT treatment plan
(hypoxic) Tumor Volume (BTV) defined using PET-CT CT. A deformable image registration (DIR) was perfor-
as a hypovascularized-hypometabolic (SUVmax<3) med to better compare the CT anatomy.
junctional zone between the central necrotic and Results: Median follow up time after SBRT was
peripheral hypervascularized-hypermetabolic bulky 10.1 months (range 4.2-27.6 months). Overall, a Local
segment, avoiding the tumor microenvironment (20 Control Rate (LCR) of 80% was obtained (85%, 23/27
patients). Immunohistochemistry was performed on the in surgical vs 75%, 18/24 in nonsurgical pts; p=0.32).
available tissue samples to explore for the modifica- Tumor relapse occurred in 30 pts (59%): distant alone
tions within the tumor microenvironment. in 20 pts, LRF only in 6 pts and a combination of distant
Results: 3 treatment groups were comparable in and LRF in 4 pts. Concerning LRFs, 7 were exclusively
terms of performance status, histology and disease in field and 3 a combination of in and out field failure.
stage. Table 1 summarizes the results. Median follow Median Local Progression Free Survival from SBRT
up was 12.7 months (range: 4-27), mean bulky diame- was 9 months (8.5 vs 9.7 months in surgical vs nonsur-
ter: 8.1 cm (range: 6-13.5). Histology: 39% squamous, gical pts; p=0.78). The dosimetric evaluation showed
51% adenocarcinoma, 10% other. that all in field failures occurred inside the area covered
Conclusions: Exploitation of the tumoricidal radia- by 95% of the prescribing isodose, with extent in the
tion-hypoxia-induced BE and AE by SBRT-PATHY area immediately close to the PTV. Interestingly, we
may potentially enhance the radiotherapy therapeutic didn’t observe isolated nodes recurrences in the ENI
ratio. area. At the last follow-up 34 pts (67%) were alive, with
a median Progression Free Survival of 16.3 months and
a median Overall Survival of 18.6 months from the time
of diagnosis.
Table 1. Summary of the results.

Conclusions: SBRT for PC pts pretreated with che-


motherapy was able to provide an acceptable LCR and
the lack of ENI didn’t significantly increase the rate of
failure in the regional nodes area.

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Oral Communications

CO047 CO048
THE PROGNOSTIC ROLE OF FDG PET/CT BEFO- ARE WE READY FOR A PARADIGM SHIFT FROM
RE COMBINED RADIO-CHEMOTHERAPY IN ANAL HIGH-DOSE CONVENTIONAL TO MODERATE
CANCER PATIENTS HYPOFRACTIONATED RADIOTHERAPY IN INTER-
S. Manfrida1, L. Leccisotti1, V. Privitera1, R. Barone2,
D. Ripani1,3, L. Tagliaferri1, V. Masiello1, F. Marazzi1,
MEDIATE-HIGH RISK PROSTATE CANCER? A

V. Frascino1 , M.A. Gambacorta1,3, V. Rufini1,3,


SYSTEMATIC REVIEW OF RANDOMIZED CON-

A. Giordano1,3, V. Valentini1,3
TROLLED TRIALS WITH TRIAL SEQUENTIAL

1Dipartimento di Diagnostica per Immagini,


ANALYSIS
L. Ferella1,3, E. Limoncin5, F. Vittorini2,
Radioterapia Oncologica ed Ematologia, Fondazione A. Chalaszczyk3, C. Sorce3, G. Grimaldi3, F. Rossi3,
Pol. Universitario A. Gemelli IRCCS Roma; 2Radius C. Bertoldo3, P. Franzese3, V. Ruggieri3, E. Varrassi3,
S.r.l.-Budrio, Bologna;  3Università Cattolica del Sacro M. Di Staso3, G. De Lorenzo Ramon2, F. Marampon6,
Cuore, Roma, Italy V. Tombolini6, C. Masciocchi4, G.L. Gravina3
1Radiotherapy Unit, Centro di Tomotherapy Aosta;
Aims: FDG PET/CT could be useful in the progno- 2University of L’Aquila, Service of Medical Physic;
stic stratification of anal cancer patients. Therefore, we 3University of L’Aquila, Division of Radiotherapy;
retrospectively assessed the prognostic value of FDG 4University of L’Aquila, Division of Radiology;
PET/CT parameters, including MTV and TLG measu- 5University of Tor Vergata, 6La Sapienza University
red within the primary tumour and the involved lymph
nodes, before definitive RCT in anal cancer patients. Aim: To evaluate efficacy and late toxicity of mode-
Methods: Anal cancer patients with positive baseli- rate hypofractionated (HFRT) over high-dose (>76 Gy)
ne FDG PET/CT who underwent combined RCT treat- conventional radiotherapy (CRT) in a non-inferiority
ment with curative intent from May 2011 to February perspective.
2018 were included. PET parameters were measured Methods: The study inclusion criteria were RCTs
within the primary tumours and the involved nodes: pri- involving patients with localized intermediate and high-
mary tumour (T)-SUVmax, T-SUVpeak, T-SUVmean, risk PCa and treated with moderately hypofractionated
T-MTV, T-TLG, whole body (WB)-MTV and WB- regimens (HRT) or high-dose CRT. High-dose CRT was
TLG. Kaplan-Meier curves, Cox-regression analysis, defined as a cumulative dose of 76 Gy or greater deli-
Mann-Whitney U test and logistic regression machine vered in conventional fractionations. The treatment
learning technique were used to test for associations volumes had to be the same for both arms and had to
between clinical data, metabolic parameters and outco- include the whole prostate, with or without the seminal
mes as overall survival (OS), disease specific survival vesicles or pelvic lymph nodes. All RCTs using dose
(DSS), metastatic free survival (MFS), disease free sur- per fraction greater than 4 Gy were excluded. HFRT
vival (DFS), local relapse free survival (LRFS) and regimens were deemed non-inferior to high-dose CRT
colostomy free survival (CFS). if the computed CI for the overall RR did not exceed the
Results: Fifty-nine patients were included in the non-inferiority margin of 7%.
study. Median follow-up was 28 months. Higher pre- Results: A total of 2481 men were enrolled in the
treatment WB-MTV, T-TLG and WB-TLG were associa- four RCTs included in this systematic review with 1249
ted with worse OS (p=0.025, 0.021 and 0.02 respecti- men receiving HFRT and 1232 receiving high-dose
vely). PET parameters resulted also statistically signifi- CRT, respectively. When the prespecified margin, cor-
cant for DSS, DFS and CFS (p=0.032, 0.043, 9×10-4 for responding to a critical RR of 0.930 for CCS, OS and
WB-TLG). Cox analysis showed that PET parameters BFS, was used all efficacy outcomes satisfied the crite-
are significant predictors of OS (for this outcome also ria for the non-inferiority analysis indicating the non-
age is significant), DSS, DFS, CFS and LRFS. On mul- inferiority of HFRT regimens over high-dose CRT in
tivariate analysis, age, stage, T-SUVpeak, WB-MTV and the medium term period. The analysis of the CIs boun-
T-TLG resulted significantly related to OS. In addition, a daries of the computed RRs indicated that they excee-
further stratification for patients with advanced stage ded the pre-specified margin indicating that the eviden-
(cT3-T4 any N or any T N+) showed that MTV and TLG, ce concerning the non-inferiority of HFRT regimens
measured within the primary tumour and the involved over high dose CRT was inconclusive. We deemed our
nodes, are significantly higher in patients dead for can- meta-analysis conclusive, in demonstrating that HRFT
cers in patients with relapse or colostomy. regimens were non-inferior over high-dose CRT, when
Conclusions: Pre-treatment metabolic parameters the required sample size is reached and the cumulative
measured within the primary tumour and the involved Z-curves cross the futility boundaries constructed by
nodes may represent additional new biomarkers for TSA. The required sample size to consider meta-analy-
estimating prognosis in anal cancer patients and for sis conclusive was based on an alpha error 5%, a beta
modulating the treatment. error 0.20-0.10 (study power in the range of 80%-90%)
Legend of acronyms and a non-inferiority margin 7%. TSA analysis indica-
maximum Standardized Uptake Value (SUVmax) ted that the accrued sample size (2481 patients) excee-
metabolic tumour volume (MTV) ded the required sample size (2007 patients for OS,
total lesion glycolysis (TLG) 2464 patients for CSS and 2416 patients for BFS) need

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

to confirm the non-inferiority of HFRT regimens in or Targeted Therapy (TT) for the treatment of brain
terms of efficacy parameters. metastases (BM) from Non Small Cell Lung Cancer
Conclusions: Noninferiority analysis indicates that (NSCLC). Aims of the study were Local Progression
moderate HFRT regimes are non-inferior over high- free Survival (L-PFS), Distant Progression Free
dose CRT in the medium-term. Inconclusive is the evi- Survival (D-PFS), Overall Survival (OS) and Safety.
dence for the late toxicity. Longer follow-up will provi- This a multicenter study by Brain and the Thoracic
de a more clear answer concerning the non-inferiority Oncology Group of Airo (Italian Association of
of HFRT regimens in the long-term period. Radiation Oncology).
Methods: Data about patients treated with concomi-
tant IT or TT and RS were retrospectively collected.
Concurrent time was considered a period of 4 weeks. L-
PFS and D-PFS were defined as the time from RS to
CO049
local progression of the treated lesions and to the appea-
rance of new BM, respectively. Patients should have at
RESULTS FROM THE TTIRS TRIAL: A RETRO-

least a follow up of 3 months. Safety results were repor-


SPECTIVE MULTICENTER ANALYSIS OF THE

ted according to the CTCAE v4.1. Kaplan Meyer analy-


ASSOCIATION BETWEEN CONCOMITANT

sis of survival was performed.


TARGETED THERAPY OR IMMUNOTHERAPY AND
RADIOSURGERY FOR THE TREATMENT OF BRAIN
METASTASES FROM NON SMALL CELL LUNG
CANCER ON BEHALF OF BRAIN AND THORACIC Table 1. Patients and treatments characteristics.
ONCOLOGY NATIONAL GROUP OF AIRO
S. Scoccianti1, E. Olmetto1, R. Di Franco2,
P. Anselmo3, G. Beltramo4, C. Mantovani5, M.F. Osti6,
V. Pinzi7, N. Giaj-Levra8, A. Bruni9, P. Matteucci10,
S. Pedretti11, E. Giudice12, P. Tini13, M. Krengli14,
P. Ciammella15, F. Pascqualetti16, M. Trignani17,
A. Merlotti18, V. Borzillo2, D. Franceschini19,
C. Delli Paoli1, E. Maranzano3, U. Ricardi5,
P. Navarria19, V. Scotti1
1Radiation Oncology Unit, Department of Experimental

and Clinical Biomedical Sciences “Mario Serio”, AOU


Careggi, University of Florence; 2Istituto Nazionale
TUMORI-IRCCS--Fondazione G. Pascale, Napoli;
3Radiotherapy Oncology Centre S. Maria Hospital,

Terni; 4Cyberknife Centro Diagnostico Italiano Milano;


5Department of oncology, Radiotherapy unit, University

of Turin; 6Uoc radioterapia Aou sant’Andrea facoltà


medicina e psicologia Universita Sapienza, Roma; 7Uo
radioterapia Fondazione IRCCS istituto neurologico
Carlo Besta, Milano; 8Dipartimento di radioterapia
oncologica avanzata, IRCCS Ospedale Sacro Cuore
Don Calabria, Negrar, Verona; 9Radiotherapy Unit,
Department of Oncology and Hematology, University
Hospital of Modena; 10Radioterapia Oncologica
Campus Biomedico Roma; 11ASST Spedali Civili di
Brescia e Università degli studi di Brescia, U.O.
Radioterapia oncologica, Brescia; 12Dipartimento di
Oncoematologia, UOC di Radioterapia, Policlinico
Universitario Tor Vergata, Roma; 13Radioterapy unit,
University of Siena; 14Radiation Oncology, University
Hospital Maggiore della Carità, Novara;
15Radioterapia Oncologica, AUSL-IRCCS Reggio
Results: Data of 254 NSCLC patients from 19
Emilia; 16Radiation Oncology, Azienda Ospedaliero
Italian radiotherapy centers were analyzed. Patients
Universitaria Pisana, Pisa; 17U.O.C. Radioterapia
were treated from 05/01/2007 to 29/11/2018. Median
Oncologica, Ospedale Clinicizzato SS Annunziata,
age was 65 years (range 33-86). A total of 499 BM were
Università G.D'Annunzio, Chieti; 18Radiation Oncology
treated: 184 (72%) patients were treated in a single frac-
A.S.O. S.Croce e Carle, Cuneo; 19Radiotherapy and
tion while 70 (28%) with Hypo-Fractionated radiothe-
Radiosurgery Department Humanitas Research
Hospital, Rozzano (MI), Italy
rapy. The most used drugs were Nivolumab (22%),
Pembrolizumab (16%), Erlotinib (15%), Gefitinib
Aims: To investigate the association between con- (13%) and Crizotinib (12%). Patients and treatments
comitant RadioSurgery (RS) and Immunotherapy (IT) characteristics are summarized in Table 1. Eleven

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Oral Communications

patients were lost during follow up (FUP). After a Methods: We collected the data of advanced
median FUP of 7 months L-PFS, D-PFS and OS were NSCLC pts treated with N for at least 24 months, after
48 months (range 30m-69m), 12 months (range 9m- a first-line therapy. Baseline characteristics, responses
16m) and 7 months (range 2m-15m) respectively. to treatment and adverse events were described. Data
Nivolumab compared to Pembrolizumab seemed to related to subsequent lines of therapy, previous and/or
show a better L-PFS (HR: 0.7 CI 95%: 0.14-3.04), D- concurrent treatments, including radiotherapy (RT),
PFS (HR 0.79 CI 95% 0.35-1.77) and OS (HR: 0.5 CI were available.
95% 0.2-1.7) without reaching a statistical significance. Results: From June 2015 to the time of analysis, 53
Among TT Erlotinb compared to Gefitinb and advanced NSCLC pts were selected. Median age was
Crizotinib showed a better OS while D-PFS showed a 68.2 years; males were 74%, females 26%; the majority
trend in favor of Gefitinib. Grade 2 and 3 Radionecrosis of pts (92%) were current or former smokers and 55%
were reported in 10 (4%) and 2 (1%) patients, respecti- had metastatic disease at diagnosis. Squamous histo-
vely. No other severe neurological toxicity were descri- logy was 47%, while non-squamous one 53%; none
bed. oncogene-addicted disease. 59% of pts had ≥2 metasta-
Conclusions: Our data suggest that RS and IT or TT tic sites at the start of N. Median number of N admini-
for the treatment of BM from NSCLC is feasible and strations was 62 (range 35-89). Median time to best
safe. Among IT Nivolumab seems to be associated with response was 6.4 months (range 2-20): 3 complete
a better intracranial control and OS compared to responses, 34 partial responses and 16 disease stabiliza-
Pembrolizumab, while there is not a clear difference in tions were observed. A half of pts (27) underwent RT:
terms of outcomes between different targeted agents. in 9 pts (17%) radical doses to locally-advanced thora-
Prospective data are needed to confirm our results. cic disease, in two pts post-operative RT, in 6 pts (11%)
radical doses to metastases, in 15 pts (28%) palliative
RT. RT was concomitant to N in 7 pts (13%): in all of
these N is still ongoing. At the time of the analysis, 90%
CO050
of pts are alive and 70% of pts are still on treatment
with N. N was interrupted in 16 pts for disease progres-
PRELIMINARY EVALUATION OF NIVOLUMAB

sions (7 pts), pulmonary or pancreatic severe adverse


LONG RESPONDING NSCLC PATIENTS:

events (2 pts) and for other causes in 7 patients. No


A REAL-LIFE DATA COLLECTION FROM 14

treatment-related deaths were observed. Median pro-


TUSCAN CENTERS
M. Perna, V. Scotti, C. Delli Paoli, E. Mini, G. Rossi,
L. Calabrò, A. Camerini, E. Vasile, A. Chella, S. Giusti, gression free survival was 30.7 months (range 16.8-
R. Petrioli, D. Pozzessere, F. Mazzoni, M. Turrini, 42.4). Median OS from the start of N was 31.9 months
G. Meoni, V. Fabbroni, G. Pasquini, F. Meacci, (range 18.9-42.4). Median OS from the diagnosis of
A. Lunghi, E. Baldini, L. Livi metastatic disease was 44 months (range 14.3-71.2).
After disease progression, 6 pts received further thera-
Radiation Oncology, AOU Careggi;Radiation pies.
Oncology, AOU Careggi; Oncology, San Luca Hospital; Conclusions: The present series of pts treated with
Medical Oncology, University of Florence, Careggi N for at least 2 years confirm the efficacy of this drug,
University Hospital; Oncology, Medical Oncology and showing durable responses in a subset of pts, mainly
Immunotherapy, Center for Immuno-Oncology, current or former smokers, without oncogene addiction,
University Hospital of Siena; Oncology, Medical squamous and non-squamous NSCLC. The half of pts
Oncology and Immunotherapy, Center for Immuno- needed RT. RT was delivered safely during immunothe-
Oncology, University Hospital of Siena; Medical rapy.
Oncology, Versilia Hospital; Polo Oncologico, AOU
Pisana; Unit of Respiratory Medicine, Department of
Critical Area and Surgical, Medical and Molecular
Pathology, University Hospital of Pisa; Medical
CO051

Oncology, Azienda USL Toscana Sud-Est; Medical TOLERANCE AND SAFETY OF STEREOTACTIC
Oncology Unit, University of Siena; Medical Oncology RADIOTHERAPY (SBRT) IN STAGE IV NON
Unit, Prato Hospital; Medical Oncology, AOU Careggi;
Medical Oncology, Valdarno Hospital; Medical
SMALL LUNG CANCER (NSCLC) PATIENTS

Oncology, San Giovanni di Dio Hospital; Medical


DURING IMMUNOTHERAPY (IT): A MULTICEN-

Oncology, Borgo San Lorenzo Hospital; ,Polo


TRIC RETROSPECTIVE ANALYSIS ON BEHALF

Oncologico, AOU Pisana; Radiation Oncology, AOU


OF AIRO THORACIC ONCOLOGY STUDY GROUP
M. Andolina1, A. Bruni1, P. Ciammella2, L. Falcinelli3,
Careggi; Oncology, San Luca Hospital; Oncology, San C. Greco4, N. Giaj-Levra5, D. Franceschini6,
Luca Hospital; Radiation Oncology, AOU Careggi, Italy M. Taraborrelli7, E. D’Angelo1, M. Perna8, A. Taddeo9,
Aims: Two randomized phase III trials showed A. Fozza10, R. Rossi2, M.L. Bonù9, A.R. Filippi11,
improved overall survival (OS) for Nivolumab (N) ver- P. Borghetti9, V. Scotti8
sus Docetaxel in pre-treated advanced NSCLC. A sub- 1Radiotherapy Unit, University Hospital of Modena,

set of these patients (pts) benefits of N for long term, Modena; 2Radiation Oncology Unit, AUSL - IRCCS di
with an impressive durable response. Aim of current Reggio Emilia; 3Radiation Oncology Section, Perugia
analysis is to describe a selected series of these pts. General Hospital, Perugia; 4Radiation Oncology,

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Campus Bio-Medico University of Rome; 5Radiation potential, synergystic effects on local and systemic
Oncology, IRCCS Sacro Cuore Don Calabria Hospital, disease in stage IV NSCLC pts. Ongoing studies set out
Negrar-Verona; 6Radiation Oncology Department, to understand the optimal timing, RT doses and ideal
Humanitas Research Hospital and Cancer Center, combination between RT and IT in this setting.
Milan-Rozzano; 7Radiotherapy Unit, SS Annunziata
Hospital - G. D'annunzio University, Chiet; 8Radiation
Oncology Unit, Department of Biomedical, CO052
Experimental, and Clinical Sciences, University
Hospital Careggi, University of Florence; 9Radiation
THE PROGNOSTIC SIGNIFICANCE OF

Oncology Department, ASST Spedali Civili, Brescia;


NEUTROPHIL-TO-LYMPHOCYTE RATIO IN THE
10Department of Radiation Oncology, SS. Antonio e
ERA OF HPV STATUS FOR OROPHARYNGEAL
Biagio e C.Arrigo Hospital Alessandria; 11Department
CANCER PATIENTS: SOMETHING WE NEED TO
of Medical Sciences and Infectious Diseases, Unit of
FINALLY CONSIDER?
Radiation Oncology, Fondazione IRCCS Policlinico G. Fanetti1, D. Alterio2, G. Marvaso2, S. Gandini3,
San Matteo, Pavia, Italy D. P. Rojas2, C. Gobitti1, E. Minatel1, A. Revelant1,
A. Caroli1, C.M. Francia1, O. Alessandro2,4,
Aims: IT has recently enhanced the treatment arma- A. Starzyńska5, J. Polesel6, E. Vaccher7, M.C. Rocca8,
mentarium for stage IV NSCLC as well as SBRT. M. Tagliabue9, M. Ansarin9, V. Lupato10,
Radiobiological studies and initial clinical reports sug- V. Giacomarra10, A. De Paoli1, R. Orecchia11,
gest a potential synergistic effect of SBRT and IT even G. Franchin1, B.A. Jereczek-Fossa2,4
if the mechanism is not yet completely clear. Aim of 1Division of Radiation Oncology, Centro di Riferimento
this study is to retrospectively analyze the safety, tole-
Oncologico di Aviano (CRO) IRCCS, Italy; 2Division of
rance and clinical outcome of SBRT plus IT
Radiation Oncology, IEO, European Institute of
(Nivolumab [NIVO], Pembrolizumab [PEM] or
Oncology IRCCS, Italy; 3Department of Experimental
Atezolizumab [ATE]) in advanced NSCLC patients
Oncology, IEO, European Institute of Oncology IRCCS,
(pts).
Italy; 4Department of Oncology and Hemato-oncology,
Methods: We retrospectively analyzed 49 consecu- University of Milan, Italy; 5Department of Oral Surgery,
tive pts affected by stage IV NSCLC treated with SBRT Medical University of Gdańs, Polonia; 6Unit of Cancer
given concurrently with IT from 2015 to January 2018. Epidemiology, Centro di Riferimento Oncologico di
Twenty-nine pts were male and 20 female. Mean age Aviano (CRO) IRCCS, Italy; 7Division of Medical
was 66. Adenocarcinoma was diagnosed in 79% of pts, Oncology and Immune-related Tumors, Centro di
while squamous cell carcinoma in 21%. At diagnosis, Riferimento Oncologico di Aviano (CRO) IRCCS, Italy;
16 pts had locally advanced NSCLC, while 33 stage IV. 8Division of Uro-genital and Head and Neck Medical
Thirty-three pts were submitted to chemotherapy before Oncology, IEO, European Institute of Oncology IRCCS,
receiving IT, while 16 pts received IT as first line. Italy; 9Division of Otolaryngology and Head and Neck
NIVO was administered to 26 pts, PEM to 19 and Ate Surgery, IEO, European Institute of Oncology IRCCS,
to 4 pts. Twenty six pts received SBRT concomitantly Italy; 10Division of Otolaryngology, Santa Maria degli
to IT, 15 before starting IT (within 30 days from first Angeli General Hospital; 11Scientific Direction, IEO,
cycle) and 8 after progression during IT (within 30 days European Institute of Oncology IRCCS, Italy
from the last cycle) due to oligoprogression. SBRT was
delivered to brain metastases in 38 pts, to bone lesions Aim: To evaluate the role of baseline neutrophil-to-
in 6, to the mediastinum in 2 and to other sites in 3. lymphocyte ratio (NLR) and other haematological bio-
Results: All pts were submitted to SBRT using dif- markers such as neutrophil, lymphocyte, platelet and
ferent doses and schedules: 22 pts received 12-25 Gy in monocyte count as prognostic markers in locally advan-
single fraction (Fx), 16 pts received 24-54 Gy in 3-5 Fx ced squamous cell carcinoma of the oropharynx (OPC)
and 1 pt received 40 in 8 Fx. Overall response rate was treated with definitive chemo-radiotherapy (CRT) in the
78.7%. At a median FUP of 17 months 1- and 3 year- era of HPV status.
Overall Survival were 80.5%±5.5%ES and Patients and Methods: A retrospective analysis of
42.4%±8.5%ES respectively, Cancer Specific Survival 125 patients (pts) affected with locally advanced OPC
86.6%±ES5.1% and 45.7%±8.9%ES respectively and and treated between 2010 and 2015 at two tertiary can-
progression free survival 67.7%±6.1%ES and cer centres in Northern Italy (European Institute of
28.5±8.1%ES. During FUP 30 pts experienced disease Oncology, Milan and Centro di Riferimento
progression with a mean duration time of IT of 6.1 Oncologico di Aviano, Aviano) was performed.
months (range 1-24,1); mean time to progression was Inclusion criteria were: age>18 years, stage III or IV
5.1 months. No pt had to interrupt systemic therapies (TNM 7th ed.), definitive CRT. Multivariate Cox pro-
and no severe toxicities (>G2) were found due to SBRT portional hazard models were applied to assess the
treatment. Known systemic side effects from IT were independent role of haematological markers of for pro-
observed in 10 pts: 3 pts had diarrhea, 1 pulmonitis, 2 gression-free survival (PFS) and overall survival (OS),
liver toxicity, 2 pneumonitis and 2 thyroiditis. adjusting for other prognostic factors and confounders.
Conclusion: SBRT and IT with the checkpoint inhi- Logistic models were used to assess the association
bitor represent a safe, well tolerated and efficient multi- with downstage in TNM 8th ed.
modal treatment, with the available data suggesting also Results: Median age was 61 (42-77) years and 94

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(75.2%) pts were male. HPV status was available in 102 expression of immune checkpoints (IC) (CD39, PD-1,
(81.6%) pts and among them 77 (61.6%) pts had CTLA-4, TIM3). These parameters were correlated
HPV/p16+ related OPC. Therapeutic choice consisted with response to treatment, also in the context of the
in sequential and concurrent chemo-radiotherapy as p16 status.
well as induction followed by concurrent CRT schedu- Results: Median follow up was 8 months (range: 2-
le, and it was delivered to 43 (34.4%), 71 (56.8%) and 18). Median age was 65 years (range: 35-83). 11 (55%)
11 (8.8%) pts, respectively. Median follow-up was 50 and 9 (45%) pts had a HPV + and HPV – tumors,
months (range 5-95 months). All haematological bio- respectively. Four pts (20%) underwent radical
markers significantly changed after CT/RT. A value of radiotherapy, while 16 (80%) pts received a combined
NLR≥3 was associated with poorer OS with more than treatment (12 CDDP, 4 Cetuximab). At last re-evalua-
double increased risk of death: HR=2.5 (95%CI: 1.1, tion, 13 (65%) pts presented a complete response, 1
5.5; p=0.03, adjusted for age, stage and HPV status). (5%) pt a progression disease (PD) and 6 (30%) pts
Two-year OS was 91% and 81% in pts with NLR<3 and were dead (3 PD, 2 toxicity and 1 for non-cancer related
≥3, respectively. No correlation was found between causes). CD3 TILs were more represented in tumor bio-
other haematological parameters and prognosis. psy compared to peripheral blood. There was no signi-
Prognostic value of NLR has been confirmed restaging ficant difference among TILs in responders vs non
our cohort of pts with the new TNM staging (8th ed.). responders pts (p=0.10- Figure 1A) but there was a
Conclusion: In our cohort, a baseline NLR≥3 at higher CTLA-4 expression on TILs of HPV+ vs HPV –
treatment initiation represented a negative prognostic pts (median value: 30% vs 10% - Figure 1B).
marker for OPC treated with definitive CRT. Our results Interestingly, categorizing TILs according to PD1
are in line with literature data and are confirmed after expression (PD1-, PD1 intermediate, PD1 bright) we
re-staging with last TNM. Therefore, this inexpensive observed a significant higher expression of other IC
and readily available marker could be considered for (TIM-3, CD 39) in those cells with the highest PD1
risk stratification of pts with locally advanced OPC. level (Figure 1C-1D). Intratumoral CD4+ Treg fre-
quency resulted statistically increased in cancer speci-
mens with respect to blood (Figure 1E) and Treg exhi-
bited an active functional phenotype (high FoxP3,
CO053
CTLA-4 and CD39 expression and high expression of
immune checkpoints as PD1 and TIM3); moreover
IMMUNOLOGICAL PROGNOSTIC BIOMARKERS IN

CD4+ Treg were more represented in HPV – tumours


RELATION TO HPV STATUS AND CLINICAL OUT-

compared to HPV + tumours (p=0.02- Figure 1F).


COMES IN OROPHARYNGEAL CANCER

Conclusions: The results highlight the co expres-


PATIENTS: PRELIMINARY RESULTS OF A PRO-

sion of different IC on a subset of TILs that might sug-


SPECTIVE INVESTIGATION
L. Belgioia1-2, A. Bacigalupo2, F. Missale3, S. Negrini4,
G. Filaci4, D. Fenoglio4, S. Vecchio5, G. Peretti3, gest the develop of new combinatorial protocols in
R. Corvò1-2 selected pts. The higher expression of Treg cells in HPV
1Health Science Department (DISSAL), University of
– tumours might explain the worse prognosis but
further investigation is recommended.
Genoa; 2Department of Radiation Oncology, IRCCS
Ospedale Policlinico San Martino; 3Department of
Otorinolaringology - Head and Neck surgery,
University of Genoa; 4U.O. Immunologia Clinica -
Centro di Eccellenza per le Ricerche Biomediche
(CEBR) dell’Università degli Studi di Genova e U.O.
Clinica di Medicina Interna ed Immunologia Clinica
dell’IRCCS Ospedale Policlinico San Martino;
5Department of Medical Oncology, IRCCS Ospedale

Policlinico San Martino


Background: To perform a comprehensive analysis
of the circulating and intratumoral T cell compartments
in patients affected by Oropharyngeal Squamous Cell
Carcinoma (OSCC) to search for new prognosticators
and to get insights on new possible immunotherapeutic
strategies.
Methods: From May to October 2018 we prospecti-
vely enrolled 20 patients (pts) affected by locally
advanced OSCC and treated by radiotherapy or
chemo/bio-radiotherapy. Peripheral blood and tumor
Figure 1.

biopsies were collected before treatment and evaluated


by multiparametric flow cytometry panels to delineate:
tumour-infiltrating lymphocytes (CD4+ and CD8+
TILs), frequency of CD4+ T regulatory cells (Treg),

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2 years OS nomogram. Covariates that show negative


impact on 2y OS were positive nodal status, presence of
CO054

metastasis, PS ECOG >1, Age, dose < 66Gy and inter-


ruption days of radiotherapy >3. ROC AUC for training
DEVELOPMENT OF OVERALL SURVIVAL PREDIC-

set, testing set and whole dataset for OS at 2, 3 and 5


TIVE NOMOGRAMS IN PATIENTS WITH LOCALLY

years are shown in Table 1.


ADVANCED OROPHARYNGEAL CANCER COMING

Conclusions: A large multidimensional database


FROM ITALIAN PRO.M.E.THE.O. GROUP
S. Longo1-2, A. Pesce1, G. Chiloiro1-2, P. Bonomo3,
A. Bacigalupo4, A. Merlotti5, E. D'Angelo6, P. Franco7, allow the creation of a multifactorial OS prediction
I. Desideri8, L. Belgioia9, N. Denaro10, B. Meduri5, model in LAOC treated by RT-Cet. An external valida-
F. Arcadipane11, J. Lenkowicz2, R. Autorino2, tion should be needed to confirm the robustness of the
M. Massaccesi2, F. Miccichè2 model for a possible clinical application for a perso-
1Università Cattolica del Sacro Cuore, Rome;
nalyzed approach.
2Fondazione Policlinico Universitario A. Gemelli

IRCCS – Rome; 3Azienda-Ospedaliero-Universitaria
Table 1.

Careggi- University of Florence, Department of


Radiation Oncology, Florence; 4Policlinico San
AUC Train Test Overall

Martino, Radioterapia, Genova; 5S. Croce and Carle 2 years 0.787 0.763 0.793
Teaching Hospital, Department of Radiation Oncology, 3 years 0.763 0.706 0.767
Cuneo; 6Azienda Ospedaliero Universitaria- Policlinico 5 years 0.741 0.852 0.771
di Modena., Radioterapia, Modena; 7University of
Turin, Department of Oncology- Radiation Oncology,
Turin; 8Azienda-Ospedaliero-Universitaria Careggi-
University of Florence, Radiation Oncology, Florence;
9Dip. Scienze della salute DISSAL Università di

Genova, Radioterapia, Genova; 10S. Croce and Carle


Teaching Hospital, Department of Oncology, Cuneo;
11AOU Citta' della Salute e della Scienza, Department of

Oncology- Radiation Oncology, Turin, Italy


Aims: Treatment of oropharyngeal cancer is
moving toward a tailored treatment based on stratifica-
tion of risk group, which requires patient-specific esti-
mates of survival outcomes. Aim of this study is to
develop a predictive model of overall survival (OS) for Figure 1.
patients (pts) with locally advanced oropharyngeal can-
cer (LAOC) treated with radiotherapy (RT) in associa-
tion with Cetuximab (Cet), coming from
PRO.M.E.THE.O. (PRedictiOn Models in Ent cancer
CO055

for anti-EGFR based THErapy Optimization) italian OCCURRENCE OF SYMPTOMATIC CARDIAC


multicentric dataset. EVENTS IN EARLY BREAST CANCER PATIENTS
Methods: Pts with LAOC treated with RT-Cet RECEIVING CHEMOTHERAPY, TRASTUZUMAB,
coming from 6 centres (Cuneo, Firenze, Genova,
Modena, Roma, Torino), were considered for this
OR THEIR COMBINATION WITH OR WITHOUT

analysis. We take into account different variables: age at


RADIOTHERAPY: AN ANALYSIS OF REAL WORLD

diagnosis, gender, PS ECOG, TNM stage, total dose at


DATA
S. Di Cosimo1,#, M. Carmen De Santis2,#, A. Trama3,
CTV High Risk, fractionation, overall treatment time, C. Giandini2, P. Minicozzi4, L. Lozza2,
RT interruption days. Follow-up times (2, 3, and 5 R. Valdagni2,5,6, G. Corrao7, G. Apolone8, M. Franchi7
years) for the OS were used as the model outcome. Pts #Equally contributed
were randomly divided into a training set (group A) cor- 1Biomarker Unit, Department of Applied Research and
responding to 80% of dataset and validation set (group Technological Development, Fondazione IRCCS Istituto
B) representing the remaining 20%. A binary logistic Nazionale dei Tumori, Milan; 2Radiation Oncology 1,
regression model was trained on group A with stepwise Fondazione IRCCS Istituto Nazionale dei Tumori,
feature selection based on Akaike's information crite- Milan; 3Evaluative Epidemiology Unit, Fondazione
rion (AIC). The model was then performed on testing IRCCS Istituto Nazionale dei Tumori, Milan;
set. ROC AUC and confusion matrix statistics at 5 thre- 4Analytical Epidemiology and Health Impact Unit,
shold were used as performance criteria. Nomograms Fondazione IRCCS Istituto Nazionale dei Tumori,
were performed at 2, 3 and 5 years. Milan; 5Prostate Cancer Program, Fondazione IRCCS
Results: Overall 218 pts were collected and 183 had Istituto Nazionale dei Tumori, Milan; 6Oncology and
the selected variable and were analyzed in this study. Hemato-oncology, Università degli Studi di Milano,
OS predictive models were developed and represented Milan; 7Laboratory of Healthcare Research &
by nomograms at 2,3 and 5 years. Figure 1 represent the Pharmacoepidemiology, Unit of Biostatistics,

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Oral Communications

Epidemiology and Public Health, Department of starting treatment with T+/-CT. RT-adjusted HR for
Statistics and Quantitative Methods, University of SCEs versus non SCEs in the whole patient cohort was
Milano-Bicocca, Milan; 8Scientific Directorate, 1.32, CI 0.35-4.92 during the first year of F/U. KM of
Fondazione IRCCS Istituto Nazionale dei Tumori, SCEs during the 9-year observational period in T- and non
Milan, Italy T-users treated or not with RT during the first year from
starting treatment with T are reported in the Figure 1.
Aims: To assess symptomatic cardiac events (SCEs)
Conclusions: Pts receiving T+/-CT are less likely to
in a large and unselected cohort of early breast cancer
be irradiated. Nevertheless, RT does not affect the
(BC) patients (pts) treated with Trastuzumab (T)+/-che-
occurrence of early SCEs, which are instead associated
motherapy (CT)+/-radiotherapy (RT).
with T+/-CT exposure. The occurrence of late SCEs in
Methods: Starting from healthcare administrative
irradiated T- and non T-users deserve further analysis.
database, ie clinical discharge records and drug pre-
scriptions available in the Lombardy region (Italy), we
surveyed a cohort of pts diagnosed with BC between
01/2008 and 12/2011, treated with T+/-CT+/-RT, and
CO056

monitored until 12/2016. The effect of RT on the occur- DEFINITIVE DATA OF TOGETHER STUDY
rence of SCEs, including heart failure and cardiomyo-
pathy as per ICD9-CM codes, in pts treated with CT or
TREATMENT OUTCOME OF METASTATIC LESIONS

T+/-CT with or without RT was estimated using the


FROM RENAL CELL CARCINOMA UNDERGOING

Kaplan-Meier (KM) method, and RT independent pre-


EXTRA-CRANIAL STEREOTACTIC BODY

dictive value was assessed by the Cox regression


RADIOTHERAPY
E. Lattanzi1, S. Buti2, M. Bersanelli2, M. Manicone1,
model. F. Salaroli1, S. Gianni1, C. Grondelli1, A. Viansone2,
A. Leonetti2, C. Masini3, R. Ratta4, G. Procopio4,
F. Maines5, R. Iacovelli6, C. Ciccarese6, M.G. Vitale7,
U. De Giorgi8, C. Mucciarini9, M. Maruzzo10,
G. Prati11 S. Andreani1, C. Di Carlo1, N. D’Abbiero1
1Radiotherapy Unit, University Hospital of Parma;
2Medical Oncology Unit, University Hospital of Parma;
3Medical Oncology Unit, AUSL-IRCCS Reggio Emilia

3; 4Medical Oncology Unit, Istituto Nazionale Tumori


Milano; 5Medical Oncology Department, Santa Chiara
Hospital, Largo Medaglie d'Oro, Trento; 6Medical
Oncology, Fondazione Policlinico Universitario A.
Gemelli IRCCS, Roma; 7Department of Oncology and
Haematology and Respiratory Disease, University
Hospital of Modena, Modena; 8Department of Medical
Oncology, Istituto Scientifico Romagnolo per lo Studio e
la Cura dei Tumori IRCCS, Meldola; 9Medical
Oncology Department, General Hospital of Carpi,
Carpi; 10Medical Oncology Unit 1, Istituto Oncologico
Veneto, IOV-IRCCS, Padova,Day Hospital Oncology,
Ospedale Civile di Guastalla, Reggio Emilia, Italy
Aims: stereotactic body radiation therapy (SBRT)
use has increased overtime for metastatic renal cell car-
cinoma (mRCC) patients management, with a likely
good control of irradiated lesions. Recently, a wide
range of retrospective reports contributed to configure
the landscape of the current clinical practice in this
Figure 1.

field. We planned a retrospective multicenter Italian


Results: RT was not associated with increased risk study, with the aim of investigating the outcome of
of SCEs among 2,927 BC pts treated with T+/-CT and treatment with SBRT for non-brain secondary lesions in
7,908 pts treated with CT alone, Hazard Ratio (HR) mRCC patients. Methods: all consecutive metastatic
1.00, 95% Confidence Interval (CI) 0.74-1.34. After 1:2 non-brain and non-only-bone lesions from mRCC
matching for age, date of treatment start, and pre-exi- underwent SBRT at five Italian institutions from
stent cardiovascular risk factors (CRFs), we found that January 2015 to June 2017 were considered. The pri-
pts treated with T+/-CT (T-users=2,809) were less mary endpoint of the study was the lesion-PFS, calcula-
likely to receive RT as compared to those treated with ted from SBRT initiation to the local progression of the
CT alone (non T-users=5,618), 69% versus 72.3%, p= irradiated lesion. The techniques used for treatment
0.002. A total of 140 pts experienced a SCE, 52 (1.8%) planning and delivery of SBRT were quite homoge-
and 88 (0.2%) were T- and non T-users, respectively. neous, according to the local clinical practice of each
Most of these events occurred during the first year from center. To execute simulation patients were accommo-

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

dated in setup position using specific personalized scription dose (PD); D2cc of bladder <80% PD. For the
immobilization systems. CT scan was performed using urethra: the dose received by 1% of volume (D1%)
2 mm slice thickness with or not intravenous contrast. <115% PD and D10% <110% PD. The prescription for
Gross Tumor Volume (GTV) and regional Organs at the target was D90% >95% PD. Results: After a
Risk (OaR) were delineated by a Radiation Oncologist. median follow-up of 6 years (range=6-160 months)
GTV was defined using simulation CT scan fused with overall survival and cancer-specific survival rates were
MRI and/or PET-CT. PTV was created with an expan- 90% and 97% respectively. Biochemical disease-free
sion around the GTV that depends by the lesion’s cha- rate resulted 78%; for low and intermediate risk bioche-
racteristic and the patient’s compliance. A 5 to 10 mm mical free disease rate was 85%, whereas for high risk
isotropic or not margin was added to the GTV. The dose disease was 62%. Regarding dosimetric aspects, we
prescription was to the PTV or to an isodose line, obtained satisfactory dose distributions in terms of
making an inhomogeneities inside the target. RT techni- planning target volume (PTV) coverage (D90%>100%
que was Intensity Modulated Radio Therapy (IMRT), PD), with a strict respect of OAR constraints.
mainly Arc Therapy. RT schedules used by the five trea- Genitourinary (GU) and gastrointestinal (GI) acute
ting centers were quite homogeneous. Patient position toxicity > G2 was observed in 28% of patients. Late
was evaluated daily with cone beam CT before each toxicity > G2 was very low (2.2 %), while only 3
treatment session. patients reported G3 late toxicity (0.8%), which consi-
Results: 57 extracranial metastatic lesions from 48 sted in GU toxicity. Conclusions: With a median fol-
patients with primary mRCC underwent SBRT. The low-up of 6 years, HDR BRT was shown as a valid
72.4% of lesions were progression-free at 40 months, treatment modality for patients with localized prostate
with significantly better lesion-PFS for small metastatic cancer in terms of both biochemical and local control,
lesions. SBRT was safe and the local disease control as well as toxicity. Future studies can be addressed to
was 87.7%. After SBRT 37.5%of patients permanently evaluate the quality of life in this subset of patients.
interrupted systemic therapy.
Conclusions: consistently with the previous literatu-
re, our findings support the use of SBRT in selected
CO058
mRCC patients. EFFICACY AND TOXICITY FOLLOWING SALVAGE
HIGH-DOSE-RATE BRACHYTHERAPY FOR
CO057 LOCALLY RECURRENT PROSTATE CANCER
AFTER RADIOTHERAPY: A SINGLE CENTER
A 13 YEAR EXPERIENCE OF PROSTATE HDR RETROSPECTIVE ANALYSIS
BRACHYTHERAPY: ANALYSIS OF OUTCOME AND F.A. Pounou Kamga1,2, P. Blanchard3, M. Edouard4,
TOXICITY K. Fizazi5, J. Irani6, B.A. Jereczek-Fossa1,2,
C.P. Soatti1, R. D'amico1, D. Delishaj1, H. Baumert7, A. Bossi3
I.C. Fumagalli1-3 , G. Sangalli 2, F. Gherardi1, 1Oncology and Hemato-Oncology, University of Milan,
F. Bonsignore2, G. De Nobili1, A. Cocchi1, A. Vola1, Milan, Italy; 2Radiation Oncology, IEO European
F. Declich2, C. Frigerio2, A. Colombo1 Institute of Oncology IRCCS, Milan, Italy; 3Radiation
1Department of Radiation Oncology, ASST LECCO,
Oncology, Gustave Roussy, Villejuif, France; 4Medical
Lecco; 2Medical Physics Unit, ASST LECCO, Lecco; Physics, Gustave Roussy, Villejuif, France; 5Cancer
3Department of Radiation Oncology, University of
Medicine, Gustave Roussy, Villejuif, France; 6Urology,
Milano-Bicocca, Milan, Italy Hôpital Bicêtre, Le Kremlin-Bicêtre, France; 7Urology,
Groupe hospitalier Paris Saint-Joseph, Paris, France
Aim: To evaluate clinical outcomes, toxicity and
dosimetric aspects in patients affected by localized pro- Aims: According to the NCCN guidelines, Salvage
state cancer treated with 3D conformal high dose rate Brachytherapy is a treatment option for pathologically
(HDR) brachytherapy (BRT) as monotherapy (1,2,3). confirmed local recurrence after EBRT or brachythe-
Materials and Methods: From March 2004 to October rapy. We retrospectively evaluated the feasibility and
2017, 277 patients with prostate cancer (T1c- the toxicity of high dose rate (HDR) brachytherapy at
T2cN0M0) were treated in our institute using 3D our institution.
conformal HDR brachytherapy as monotherapy with a Methods: Between November 2013 and February
temporary implant. The mean age was 67 years with a 2018, 30 consecutive patients with biopsy proven intra-
range of 47-81 years. Of them, 116 patients were low prostatic recurrence of cancer after definitive radiation
risk, 145 at intermediate risk, and 15 at high risk. therapy underwent a salvage re-irradiation using HDR
Overall, 154 patients received 38 Gy in 4 fractions (2 brachytherapy. Treatment regimen was 24 Gy delivered
fractions/day in 2 days), 36 patients received 27 Gy in to the whole gland in 2 implants of 12 Gy performed 2-
2 fractions (1 fraction/day), and 87 patients received 19 4 weeks apart. All patients had had no severe side effect
Gy in 1 fraction. The treatment plan was elaborated of the previous radiotherapy course and underwent a
using CT based software to perform 3D conformal dose rectoscopy to ascertain the absence of radiation proctitis
planning aided by an inverse planning algorithm using prior to salvage procedure. Biochemical control was
these dosimetric constraints for organ at risk (OAR): assessed according to the Phoenix definition.
dose received by 2 cc of rectum (D2cc) <75% of pre- Secondary outcomes included survival and toxicities.

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Results: Median age at the salvage brachytherapy Version 4.0 (CTAE v4) by the National Cancer
was 68.5 years (range 61.3-83.2). The median Gleason Institute.
score at diagnosis was 7 (7-7) and at the time of bra- Results: The median age was 73.5 years. The
chytherapy 8(7-9). The median interval between salva- median gland volume was 39 cm3. Of the 30 patients,
ge HDR brachytherapy and the first radiotherapy course 22(73.3%) had a T2 disease, 28(93.3%) had a Gleason
was 9.1 years (range 0.8-22.4). The median PSA at sal- score ≤7, the median pre-treatment prostate-specific
vage brachytherapy was 4.9 ng/mL (range 1.3-40) , 14 antigen level was 8.31 ng/mL. 10 pts (33.3%) were
pts (38,9%) had hormone therapy after EBRT, 8 pts classified at high risk, 17(56.7%) intermediate and
(22,2%) had hormone therapy during brachytherapy 2(6.7%) low risk. A total of 17 patients (56.7%) recei-
and 6 pts (20%) were castration-resistant. After a ved hormonal therapy of whom 8(26.7%) were classi-
median follow-up of 1.7 years, a total of 19 pts (63%) fied at high-risk, 6(20%) were favorable intermediate
presented a biochemical relapse with a median time of and 3(10%) unfavorable intermediate, for a median
1.3 years (range 0.2-3.9) and 16 a clinical relapse (4 duration of 3 months. All pts tolerated the implantation
local only, 2 local and regional, 5 regional and metasta- procedure very well with minimal discomfort. No
tic and 5 metastatic only). Local relapses occurred after intraoperative or perioperative complications occurred.
a median time of 2.7 y (range 0.9-4.7). Overall toxicity The median Follow up was 20 months (range: 2-31)
profile was good, with no severe grade 3 or higher acute after treatment. 1 patient (pt) died for causes unrelated
or late gastrointestinal or genitourinary toxicity recor- to prostate cancer. Acute genitourinary toxicity grade 1
ded. (hematuria) was observed in 4 (13.8%) patients. Acute
Conclusions: Salvage HDR brachytherapy for Grade 2 urinary retention requiring the temporary use
locally recurrent prostate cancer after radiotherapy is of a catheter in the immediate postoperative period was
feasible and associated with an acceptable toxicity pro- observed in 1 (3.4%) pt. No acute or late toxicity in
file. The high rate of clinical relapse warrants further term of gastrointestinal toxicity such as anal pain, rectal
investigation to define the subgroup of patients who bleeding, diarrhea, anal ulcer and/or rectourethral fistu-
will benefit from salvage local therapy. la has been observed after treatment. Four patients had
a biochemical relapse, with a median time of 20 months
(range: 16-28), representing a 2-years actuarial relapse
rate of 82,6%. No clinical relapse or death from prostate
CO059
cancer occurred.
Conclusions: In our series, 19Gy HDR-BRT
EFFICACY AND TOXICITY OF HIGH-DOSE-RATE

demonstrates low rates of toxicity, and encouraging


SINGLE FRACTION BRACHYTHERAPY FOR

efficacy but longer follow-up is warranted before this


LOCALIZED PROSTATE CANCER: A SINGLE
treatment can be recommended more widely.
CENTER RETROSPECTIVE ANALYSIS
F.A. Pounou Kamga1,2, P. Blanchard3,
M. Edouard4, K. Fizazi5, J. Irani6, B.A. Jereczek-
Fossa1,2, H. Baumert7, A. Bossi3 CO060
1Oncology and Hemato-Oncology, University of Milan,

Milan, Italy, 2Radiation Oncology, IEO European


IMPLEMENTATION OF COMBINED INTRACAVI-
Institute of Oncology IRCCS, Milan, Italy, 3Radiation
TARY AND INTERSTITIAL BRACHYTHERAPY IN
Oncology, Gustave Roussy, Villejuif, France, 4Medical
THE TREATMENT OF LOCALLY ADVANCED
Physics, Gustave Roussy, Villejuif, France; 5Cancer
CERVICAL CANCER
Medicine, Gustave Roussy, Villejuif, France;6Urology, F. Piccolo¹, B. Pappalardi¹, M. Carrara¹, C. Tenconi¹,
Hôpital Bicêtre, Le Kremlin-Bicêtre, France, 7Urology, T. Giandini¹, E. Mazzarella¹, C. Fallai¹, A. Cerrotta¹
Groupe hospitalier Paris Saint-Joseph, Paris, France 1Fondazione I.R.C.C.S. Istituto Nazionale Tumori di

Milano S.C. Radioterapia 2, Italy


Aims: To report the efficacy and toxicity of high-
dose-rate (HDR) brachytherapy (BRT) delivered as a Aims: To improve target volume coverage with the
single fraction of 19 Gy for men with localized prostate implementation of combined intracavitary and intersti-
cancer. tial brachytherapy (ICIS-BT) in the locally advanced
Methods: From October 2015 to march 2018, 30 cervical cancer treatment.
patients with histologically proven and clinically locali- Methods: Traditionally intracavitary brachytherapy
zed prostate cancer were treated in our institution with in addition to external-beam radiotherapy (EBRT) is a
19Gy single fraction HDR-BRT. Patients were classi- standard treatment for locally advanced cervical cancer.
fied into risk group according to the NCCN guidelines. In patients with large-volume tumors at the time of bra-
All patients had a staging MRI. Treatment was delive- chytherapy, with minor parametrial response, and/or in
red using transrectal Ultrasound (TRUS) planning, with the case of unfavorable topography, intracavitary tech-
19Gy prescribed to the prostate with no margins. nique is not optimal choice. In these situations additio-
Follow up (FU) was performed at 1, 3 and 6 months nal interstitial brachytherapy has been applied to impro-
after implantation, and every 6 months afterwards. ve target coverage. In our department, from October
Biochemical failure was defined according to the 2017 to October 2018, eleven patients were treated
Phoenix definition. Toxicity was reported according to using combined ICIS-BT for primary cervical cancer.
the Common Toxicity Criteria for Adverse Event, The morphological and/or dimensional features of the

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target volume (i.e. ≥30 cc) drove our choice. All Conclusions: Brachytherapy is a part of the stan-
patients received EBRT (VMAT) with concomitant che- dard treatment for cervical uterine cancers in the locally
motherapy and sequential brachytherapy boost. The advanced stage. In patients with large-volume tumors at
prescribed dose was 45 Gy in 25 fractions over 5 weeks. the time of brachytherapy, with minor parametrial
Chemotherapy regimen was weekly Cisplatin response, and/or in the case of unfavorable topography,
(40 mg/m2). Image-guided adaptive brachytherapy the implementation of the interstitial technique alongsi-
(IGABT) based on magnetic resonance imaging (MRI) de the intracavity technique allows to guarantee an ade-
was performed for all 11 patients. Imaging technique quate coverage of the target, with a consequent better
and volume definition were in accordance to the recom- local control of the disease.
mendations from the Gynecological (GYN) GEC
ESTRO working group. GTV, High Risk CTV (HR-
CTV), Intermediate Risk CTV (IR-CTV), bladder, rec-
CO061
tum and sigmoid were delineated at the time of each
brachytherapy fraction on para-axial MR images with
ACTINIC VAGINITIS IN PATIENTS TREATED WITH

the applicator in place. Dose-volume histograms were


VAGINAL HDR BRACHYTHERAPY IN POST-

calculated to evaluate doses to tumor target and organs


OPERATIVE ENDOMETRIAL CANCER FIGO STAGE

at risk. The total dose prescribed was 28 Gy in 4 frac-


I: ROLE OF HYALURONIC ACID AND AMINO ACID

tions. EBRT and brachytherapy cumulative doses were


VAGINAL CREAM
V. Chiofalo, A. Mussano, S. La Sala, M. Bai, F. Perez
evaluated by calculation of a biologically equieffective
Playan, A. Samaria, S. Gribaudo
dose in 2 Gy per fraction (EQD2) using the linear-qua-
dratic model with α/β = 10 Gy for tumor effects and Department of Oncology, Radiation Oncology,
α/β = 3 Gy for late normal tissue damage. Acute geni- University of Turin, School of Medicine, A.O.U., Città
tourinary, gastro-enteric and vaginal toxicity was moni- della Salute e della Scienza di Torino; Department of
tored at each fraction and recorded according to the Oncology, Radiation Oncology, A.O.U., Città della
CTCAE criteria version 4.03. The planning aims, accor- Salute e della Scienza di Torino- P.O. Sant'Anna - S.S.
ding to the EMBRACE II protocol, have been achieved Radioterapia, Italy
for all 11 patients (i.e. D90 for the HR-CTV should be Aims: Actinic vaginitis is the most common Vaginal
between 90 and 95 Gy and for D98 for the GTV above Brachytherapy (VBT) related toxicity, often heavily
95 Gy). Also the hard constraints for the organs at risk affecting women’s sexual QoL due to additional altera-
were never exceeded (D2cm³ of the bladder below 80 tions as symptomatic inflammation and dyspareunia. A
Gy, D2cm³ of the rectum below 65 Gy, D2cm³ of the hyaluronic acid and aminoacids (HA+AA) vaginal
sigmoid/bowel below 70 Gy). To demonstrated that the cream is a medical device acting as anti-inflammatory,
implementation of interstitial component was essential recommended in prevention of actinic vaginitis caused
to improve target dose coverage, the treatment of the 11 by the radiotherapy of the pelvic district. Aim of this
patients were rescheduled avoiding interstitial needles work was to evaluate the efficacy of HA+AA vaginal
dose contribution. The D90 to HR-CTV obtained with cream in prevention of vaginal mucositis after adjuvant
ICIS-BT and without the use of needles were compared. HDR-VBT.
Results: Brachytherapy treatment was well tolera-
ted by all 11 patients. Patients didn’t show G3 toxicities
or higher. Figure 1 shows the variation of the D90 CTV-
HR for each of the eleven patients and one treatment
fraction, with and without the contribution of the inter-
stitial needles. The average gain in terms of target cove-
rage was of 25% in favor of the ICIS-BT treatments.

Figure 1. Figure 1.

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Methods: A prospective observational study was spective study with the purpose of evaluate feasibility,
conducted over a 26-month accrual period. From acute and late toxicity and preliminary outcome of a
January 2014 to March 2016 we enrolled 120 women single institution experience of accelerated partial brea-
(aged 53-80 years) who underwent surgery for endome- st re-irradiation with adjuvant interstitial HDR bra-
trial carcinoma stage I and adjuvant HDR-VBT (30 chytherapy (BT).
Gy/5 fractions), divided in 2 groups. Treatment Group: Material and Methods: Between January 2011 and
60 women treated with HA+AA vaginal cream twice September 2015, 31 consecutive patients with histolo-
daily for 4 weeks, starting simultaneoulsy to VBT. gically confirmed recurrent breast cancers after conser-
Control Group: 60 patients did not undergo any treat- vative surgery and conventional whole breast radiothe-
ment during and after VBT. No concomitant medication rapy were retreated with a second conservative surgical
was allowed over the period of treatment and observa- resection and reirradiated by adjuvant HDR-BT. A dose
tion. Patients were examined at the time of admission of 34 Gy in 10 fractions, 2 fractions per day with a
(T0), one month, 3 months and 1 year after treatment. minimal interval of 6h was delivered.
Subjective parameters, including CTCAE 4.03 scale for Results: Follow-up is available for 29 patients. The
AEs and objective assessment, including inflammatory procedure was well tolerated in all patients. No acute
signs inspected by the physician, were investigated. epidermitis or soft tissue side effects higher than grade
Results: 3 months after VBT, the treated group 2 were recorded, with good cosmetic results in all
showed a statistically significant improvement (P<0.05
patients. Local recurrence occurred in 2 patients (6.8%)
vs. control) on subjective symptoms of inflammation,
after 32 and 42 months from BT, distant metastases
dryness and pain. One year after VBT, further statisti-
were observed in 10.3% of women. After a median fol-
cally improvement was observed, especially in the sub-
set of patients evaluated for stricture. Rates of G0 vagi- low-up of 59.8 months (range, 17.3-96.8) the overall
nal stricture were 78% vs 52%, respectively in the treat- survival was 100%. 5-years local control and 5-years
ment group vs control and 3% vs 6% G3. G0 dryness progression free survival rate is 91% and 84%, respec-
was 80% (vs 51%) in the treatment group and G3 was tively.
only 2% (vs 6%). We observed 83% G0 vaginal pain in Conclusions: Our preliminary analysis showed that
the treatment group (vs 65%) with 0 G3 (vs 1%). HDR-BT is a feasible treatment for partial breast reirra-
Conclusions: Application of HA + AA vaginal dation offering very low-complications rate and a fast
cream on the irradiated vagina during VBT was shown procedure. Higher patient number are warranted in
to postpone the first signs of acute vaginal discomforts order to define the role of this treatment modality in the
and reduce the severity of mucosal reactions. Moreover, breast conservative management of local recurrence.
time to recover was longer, especially for exudative
epithelises, in the control group. This indicates that HA
was effective as a prophylactic but also as a therapeutic
Table 1. Patient characteristics.

measure. The results of this prospective study suggest


an interesting role of the HA+AA vaginal cream as sup-
Characteristic (31 pts) Classification number (%)

portive treatment to improve compliance and QoL in Age at the time of BT <50 years 7 (23)
patients undergoing VBT. 50-60 years 9 (29)
>60 years 15 (48)

Time to IBTR < 5 years 4 (13)


CO062
5-10 years 9 (29)
10-20 years 14 (45)
ACCELERATED PARTIAL BREAST RE-IRRADIA-

> 20 years 4 (13)


TION USING INTERSTITIAL HIGH-DOSE-RATE
BRACHYTHERAPY FOR LOCAL RECURRENCE:

Recurrence site Same quadrant of primary cancer 11 (35)


5-YEAR RESULTS
A. Vavassori1, G. Riva1,2, R. Spoto1, C. Fodo1,
Other quadrant of primary cancer 16 (52)
S. Comi3, F. Cattani3, M.C. Leonardi1, S. Dicuonzo1,
Missing data 4 (13)
R. Lazzari1, A. Luini4, R. Orecchia5,
B.A. Jereczek-Fossa1,2
1Department of Radiotherapy, IEO European Institute
BT: brachytherapy; IBTR = ipsilateral breast tumor recurrence.

of Oncology IRCCS, Milan; 2University of Milan,


Department of Oncology and Hemato-oncology, Milan;
3Unit of Medical Physics, IEO European Institute of

Oncology IRCCS, Milan; 4Breast Surgery Department,


IEO European Institute of Oncology IRCCS, Milan;
5Scientific Directorate, IEO European Institute of

Oncology IRCCS, Milan, Italy


Background and Purpose: BALESTRA
(Brachytherapy as Adjuvant Local rE-irradiation for
Salvage Treatment of Recurrent breAst cancer) is a pro-

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Conclusions: Data from our trial suggest that sin-


gle-dose IOERT in early stage breast cancer can be deli-
CO063

vered safely and with excellent results. Our long-term


recurrence rates are very low. 5 OS and DFS rate are
LONG-TERM OUTCOMES USING ELECTRON IORT

results comparable with literature data on EBRT thus


APBI FOR EARLY STAGE BREAST CANCER: THE

encouraging the use of IOERT in subset of low risk


VERONA UNIVERSITY HOSPITAL EXPERIENCE
N.Z.L. Cernusco, P. Del Bianco, N. Simoni,
M. de Liguoro, R. Micera, A. Muraglia, G. Rossi, patients with early stage breast cancer.
M. Romano, M.G. Giri, S. Guariglia, F. Pellini,
D. Lombardi, G. Pollini, C. Cavedon, R. Mazzarotto
AOUI Verona, Italy
CO064

Purpose/Objective(s): Intraoperative radiotherapy


IORT FOLLOWED BY ACCELERATED HYPOFRAC-

(IORT) it is a type of accelerated partial breast irradia-


TIONATED WHOLE-BREAST IRRADIATION

tion (APBI) and consists in the administration of radia-


VERSUS ACCELERATED HYPOFRACTIONATED

tion therapy on the tumour bed at the time of surgery.


WHOLE-BREAST IRRADIATION FOLLOWED BY

Patients deemed at low risk of locale recurrence (LR) or


SEQUENTIAL BOOST: PROPENSITY MATCHING
those deemed suitable for partial breast irradiation,
ANALYSIS OF LONG-TERM TOXICITY AND
according to the GEC-ESTRO and ASTRO recommen-
COSMETIC OUTCOME
dations,could be considered as ideal candidates for G. Grimaldi1, P. Bonfili2, C. Sorce1,
IORT. Several published studies of electron intraopera- A. Chalaszczyk1, I. Mihoci1, F. Rossi1, C. Bertoldo1,
tive radiation therapy, when delivered as APBI, have F. Vittorini3, P. Franzese4, V. Ruggieri4, M. Di Staso4,
demonstrated low recurrence rates (1.5-2.5%) at 5-year E. Varrassi4, F. Marampon5, R. Gimenez De Lorenzo3,
follow-up in ASTRO Suitable or ESTRO Good women. V. Tombolini5, C. Masciocchi1, G.L. Gravina1
1Division of Radiotherapy, Department of
We evaluated our patient cohorts treated with IORT
APBI, with follow-up up to 10 years, to answer the que- Biotechnological and Applied Clinical Sciences,
stion of long-term control. University of L'Aquila; 2Division of Radiotherapy,
Materials/Methods: From July 2006 to December Spirito Santo Hospital, Pescara; 3Division of Medical
2015, 295 patients suitable for breast-conserving the- Physics, San Salvatore Hospital, L’Aquila; 4Division of
rapy entered a single-arm phase II study and were trea- Radiotherapy, San Salvatore Hospital, L’Aquila;
5Division of Radiotherapy, Department of Radiological,
ted with IOERT, as radical treatment, immediately after
surgical resection using a single dose of 21 Gy to Oncological and Pathological Sciences, Policlinico
Dmax. Patient inclusion criteria were mostly ASTRO Umberto I, Sapienza, University of Rome, Italy
Suitable Group except for G3 grade. All patients recei- Aims: To compare the 6-years late toxicity and
ved IOERT with a mobile electron linear accelerator. cosmetic outcome in women treated by Intraoperative
Results: With a median follow-up of 84 months, 6 Radiotherapy (IORT), as anticipated boost, followed by
women (2.03%) experienced a true local recurrence hypofractionated radiotherapy (HRT) versus HRT fol-
(reappearance of the tumor in the same quadrant). None lowed by sequential boost (SB) in women with stages I-
of the patients had a new ipsilateral carcinoma (reap- II breast cancer.
pearance of cancer in another quadrant of the same Methods: Two-hundred and ninety-four women
breast). In addition, 5 women (1.69 %) developed were retrospectively studied. HRT (42.40 Gy in 16
distant metastases, 2 (0.67%) a contralateral breast can- daily fractions of 2.65 Gy) was delivered in all patients.
cer, and 9 (3%) other cancers. 22 patients (7.46%) died. Ninety-eight of them underwent IORT (10 Gy in single
Patients that recurred underwent mastectomy. 5-year fraction) during surgery and before HRT. These
overall survival (OS) was 96% (95% CI 92.9;97.8). We subjects were matched by propensity analysis with 196
analyzed characteristics associated with a high risk of women treated by HRT followed by SB (10 Gy in four
local relapse such as: age, grading, hormone profile. In daily fractions of 2.5 Gy). Late skin and subcutaneous
univariable analysis, age > 70 years (HR 2.40, 95% CI toxicity as well as cosmetic outcome were measured at
2.40;17.71 p 0.002), grading G2 (HR 9.93, 95% CI 3 and 6 years after treatments. The acute and the late
1.25;69.16 p 0.0294), and negative hormone testing skin and subcutaneous toxicity were rated according to
(HR 2.29, 95% CI 1.00;5.93 p 0.0602) have been asso- the Radiation Therapy Oncology Group (RTOG) scale
ciated with a lower 5-year OS. In multivariable analysis for early and late side effects. The cosmetic outcome,
no statistically significant value were reported except was assessed with the European Organization for
age >70 (p 0.0004). 5-year disease free survival (DFS) Research and Treatment of Cancer (EORTC) Cosmetic
was 94.3% (95%CI 90.6;96.6). Even in this case we Rating System. Differences in the incidence of toxici-
analysed characteristics associated with a high risk of ties between the two groups were evaluated by the
local relapse such as age, grading, hormone profile. In Fisher’s exact test. The analysis significance level was
univariable analysis, age > 70 years (HR 4.18, 95%CI adjusted by the Bonferroni method. According to this
1.96;8.91 p 0.002), grading G2 (HR 9.93, 95% CI correction an α error <0.0125 was considered statisti-
1.30;14.14 p 0.0167), and negative hormone testing cally significant.
(HR 2.06, 95% CI 0.94;4.54 p 0.0602) have been asso- Results: Acute Grade 2 (G2) or greater skin toxicity
ciated with a lower 5-DFS. was 31.6% in the HRT+SB group and 11.2% in the

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Oral Communications

IORT+HRT group (p=0.001). Three-years after radia- AJCC/UICC stage was: III in 36 pts and IV in 107 pts.
tion treatments, G2 or more skin late toxicity were 54 pts received neoadjuvant CHT before CTRT (2 cycle
observed in 1% vs. 10.8% (p=0.01) women treated by with CDDP-5FU schedule in 10 pts, 2-3 cycles with
IORT+HRT and HRT+SB, respectively. The rate of late TPF schedule in 44 pts) with partial response >50% of
subcutaneous toxicity was 16.7% in the HRT+SB group primary tumor (T) and Patological Nodal (PN) in 61%
and 18.4% in the IORT+HRT group (p=0.72). At 6 and 65%, respectively. IMRT-SIB dose prescription
years after radiotherapy, women treated by IORT+HRT was 70 Gy, 63 Gy and 54 Gy in 35 daily fractions to the
experienced a comparable rate of G2 or greater skin and planning target volume (PTV) of Gross tumor volume
subcutaneous late toxicity with respect to women trea- (GTV T) and PN, high risk nodes (HRN), and low risk
ted by HRT+SB (0% vs. 2.4% and 3.7% vs. 6.5% with nodes (LRN), respectively. Concurrent CT was given
p=0.57 and p=0.74). The percentage of women with a for all pts: cisplatin (CDDP) 100 mg/m2 i.v. per day
fair or poor cosmetic outcome was 15.8% in the every 3 weeks (wks) in 38 pts, CDDP 75-100 mg/m2 i.v
IORT+HRT group and 15.7% in the HRT+SB group at every 4 wks in 99, cetuximab 250 mg/mq i.v. wks in 6.
3 years (p=1.0) and was 5,6% vs. 5,4% (p=1.0) at 6 During treatment, pts received pain therapy and nutri-
years. tional support.
Conclusions: IORT as anticipated boost seems not Results: The median treatment duration was 50
adversely affect 6-years late toxicity and cosmetic out- days. Mean delivered doses were: PTV GTV T and PN
come compared with HRT followed by SB. 71.2 Gy ± 1,8 SD; PTV HRN 64,4 Gy ± 2,3 SD; LRN
Randomized controlled trials will be necessary to con- 57.1 Gy ± 1,1 SD; controlateral parotid 22,2 Gy ± 4,24.
firm our findings. Acute toxicity (according to RTOG/EORTC scales)
consisted in: mucositis G2 in 52% of pts and G3 in
35%; Xerostomia G2 in 51% and G3 in 7%, dysgeusia
in 90%, Dermatitis ≥ G2 in 62%. Mean weight loss was
Table 1. Acute Toxicity assessed by the RTOG–EORTC Acute Radiation Morbidity

3,6 Kg. RT was interrupted in 20 pts, mean 3.8 days


Scoring Criteria.

(range 1-10). Toxicity 6 months (mos) after RTCT


were: mucosal edema in 63% of the pts, Xerostomia G2
in 23%, dysgeusia in 30%, hearing loss in 7%. Late
reactions, after ≥12 mos, were: Xerostomia G1-2 in
10%; hearing loss in 7%; dysphagia in 3%; mucosal
edema in 12%. One pt underwent tracheotomy for
edema post RT and another one needed PEG for
pharyngeal necrosis. Complete response rate was
81.8% . Median follow up was 35 mos (range 2-108).
At time of this analysis : 68 pts are alive free of desease;
15 are alive with desease; 60 are died. Median Disease
free-survival and Overall Survival were 27 and 35 mos.
Conclusions: in our analysis IMRT-SIB concurrent
to CT is feasible, well tolerated with a good clinical
response.
CO065
RETROSPECTIVE ANALYSIS OF INTEGRATED
CHEMORADIATION TREATMENT OF HNSCC WITH CO066
IMRT-SIB: LONG TERM TOXICITY AND OUTCOME
A. Prisco1, V. Buoro2, M. Polsinelli1, M. G. Rugiu3, LONGITUDINAL ASSESSMENT OF WEIGHT LOSS
A. Magli1, M. A. Signor1, C. Rossetto2, M. Trovò1 AND PATIENT’S REPORTED DYSPHAGIA AFTER
1Department of Radiation Oncology, University RADIATION TREATMENT FOR HEAD AND NECK
Hospital of Udine, ASUIUD, Udine; 2Department of
CANCER
Oncology, University Hospital of Udine, ASUIUD, G. Costantino, S.M. Magrini, M. Buglione, L. Pegurri,
Udine; 3Department of Otolaryngology, University L. Costa, D. Greco, A. Alghisi, L. Maruca, A. Premi,
Hospital of Udine, ASUIUD, Udine, Italy J. Imbrescia, A. Taddeo, M. Maddalo
Radiation Oncology Department, University and ASST-
Aims: to evaluate the long term results in terms of
Spedali Civili, Brescia, Italy
toxicity, response rate and survival in patients (pts) with
advanced head and neck squamous cell cancer Aims: To analyze the factors associated with weight
(HNSCC), treated with intensity-modulated radiothe- loss and “patient-reported dysphagia” after radical or
rapy with simultaneous integrated boost (IMRT-SIB) adjuvant radiotherapy (with or without concurrent che-
schedule with concurrent chemotherapy (CHT). motherapy) treatment for Head and Neck Cancer
Methods: Between April 2010 and December 2017, (HNC).
143 consecutive pts (109 males and 34 females; mean Methods: 238 consecutive patients (pts) treated for
age 62 years) with HNSCC (88 oropharynx, 12 larynx, HNC at a single Institution (from July 2015 to
31 hypopharynx, 12 nasopharynx) were treated at our December 2017) were retrospectively analyzed.
institute with concurrent chemoradiotherapy (CTRT). Disease was localized in oropharynx (63, 26.5%),

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hypopharynx (21, 8.8%), larynx (38, 16%), oral cavity Conclusions: Weight changes and subjective
(53, 22.3%), nasopharynx ( 29, 12.2%), nose and para- dysphagia were significant in relation to many clinical
nasal sinuses (17, 7.1%) and salivary glands (10, 4.2%); and therapeutic variables analyzed. Patients reported
thyroid, skin and tumors of unknown primitiveness (7, outcomes are inexpensive and easy to use in daily prac-
2.9%) were. The longitudinal assessment of patient- tice. They can help clinicians to identify pts who need
reported dysphagia was performed only for those pts early intervention. WL after EOT highlights the need of
(58) that completed the Vanderbilt Head and Neck more intensive nutritional support in selected pts.
Symptom Survey - Italian Version 2.0 (VHNSS-IT) at
3, 6, 12, and 18 months after treatment. Maximum sco-
res of the ""swallow-solid"" (SS), ""swallow-liquid""
CO067
(SL) and ""nutrition"" (N) subscales of the VHNSS-IT
and the weight loss (WL) were correlated with clinical
PATTERNS OF FAILURE IN HIGH-RISK

and therapeutic variables and acute and late toxicities


OROPHARYNGEAL CANCER PATIENTS TREATED

(CTCAE v4).
WITH IMRT: COMPARISON OF TWO DIFFERENT

Results: Of the 238 pts analyzed only 58 completed


CTV EXPANSION MODALITIES
M.A. Teriaca, G. Stocchi, C. Bellini, G. Caramia,
the VHNSS-IT throughout the follow up. The average
A. Peruzzi, V. Maragna, C. Becherini, I. Desideri,
WL at the end of treatment (EOT) was -4,54% of basal P. Bonomo, L. Livi
weight (p=0,000). Pts kept to lose weight up to 6 months
after EOT (p=0,001 and p=0,062 at 3 and 6 months Department of Biomedical, Experimental, and Clinical
respectively). Basal weight was not reached until 18 Sciences, University of Florence; Radiation Oncology
months after EOT. Moreover WL was significantly higher Unit, Oncology Department, Azienda Ospedaliero-
in relation to concurrent chemotherapy (CC), Universitaria Careggi, Florence, Italy
enteral/parenteral (NET/NPT). In the same way acute Aims: The aim of our work was to assess the impact
(AD) and late (LD) high grade dysphagia, acute (AH) and of two different delineation approaches (anatomical vs
chronic (CH) high grade hyposcialia affected WL. SL geometric expansion) on the clinical outcome and pat-
max scores were significantly higher in elderly pts and in terns of failure of patients with oropharyngeal cancer
those with alcohol consumption. Both SS and N were (OPC).
significantly higher in relation to NPT/NET use, to AD, to Methods: We performed a retrospective analysis of
CD and to trismus. Moreover N value was significantly consecutive patients treated at our institution for OPC
higher in relation to CC, to acute mucositis, to AH and CH between January 2010 and April 2018. In 2014, our
and to chronic laryngeal edema. Table 1. local policy to delineate high risk CTV for both primary
(CTV-p) and nodal (CTV-n) GTVs shifted from an ana-
tomical expansion (AE) to a geometric expansion (GE)
modality, described as follows: - AE: CTV-p consisted
of the primary GTV plus the whole oropharyngeal ana-
Table 1. Weight, Swallow solid, Swallow liquid and Nutrition correlated to clinical

tomical compartment, edited for air cavities and anato-


and therapeutic variables and acute and late toxicities.

mical barriers; CTV-n consisted of the nodal GTVs plus


the corresponding lymph node level (delineated accor-
ding to Gregoire’s classification), including also the
level immediately adjacent to it; - GE: CTV-p consisted
of the primary GTV plus an isotropic 5 mm margin,
manually edited for air cavities and anatomical barriers;
CTV-n consisted of the nodal GTVs plus an isotropic 7
mm margin, manually edited to take into account anato-
mical barriers. Of note, an additional 5 mm margin to
the CTV-p was not added. All patients received IMRT
with 3 dose levels: the high, intermediate and low risk
CTVs received 70, 60 and 50 Gy or 69.9, 59.4 and 52.8
Gy in 35 or 33 fractions, respectively, depending on
whether a sequential or SIB technique was employed. A
3-5 mm PTV margin was added to CTV’s (3 mm in case
of daily image guidance). HPV status was not routinely
available until 2015. Median locoregional control
(LRC), PFS and OS were calculated. The relative esti-
mates of LRC and PFS at 24 months were estimated by
the Kaplan-Meier method.
Results: A total of 116 patients were included (table
1). At a median follow-up of 36 months (range: 5-108),
88 patients were alive (75.8%). The median PFS and
OS for the whole group were 74 (95% CI: 45-74) and
72 (95% CI: 64-81) months, respectively. There was no

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Oral Communications

difference between the AE and GE cohorts in terms of with simultaneous integrated boost intensity modulated
2-year LRC (86.9% vs 94.3%; median not reached; p= Radiation Therapy (SIB-IMRT) in our radiation onco-
0.28). 15 locoregional relapse were observed (13 in- logy centre. The median age was 60 years (range 43-
field and 2 marginal) with no influence of contouring 86), 83% males and 17% females, ECOG PS 0-2. The
policy adopted. primary tumor sites were 40% oropharynx, 23% larynx,
Conclusions: The adoption of a GE expansion 17% hypopharynx, 7% oral cavity, 6% unknown pri-
modality with resulting smaller high risk CTVs was not mary cancer, 4% nasopharynx, 3% others; 98% (69 pts)
associated with a detrimental impact on outcome in squamous cells cancer; PET-staged 67% IV a-b, 19%
OPC. Contouring approach did not influence the risk of III, 10% II, 4% I (AJCC-7 th edition). 52 pts received
marginal relapse. SIB-IMRT with concurrent platinum-based chemothe-
rapy or cetuximab (51 and 1 respectively), and 18 pts
underwent SIB-IMRT alone. Levels of dose were
67.5Gy (2.25Gy/fr), 60 Gy (2Gy/fr), 54 Gy (1.8Gy/fr)
for the high risk, intermediate risk and low risk PTVs
Table 1. Weight, Swallow solid, Swallow liquid and Nutrition correlated to clinical

respectively in 30 daily fractions in 40 days. The


and therapeutic variables and acute and late toxicities.

median follow-up of patients still alive was 21 months


(range 4-96). OS and PFS were estimated by using the
Kaplan-Meier method.
Results: 67 pts (96%) completed the planned sche-
dule. The median overall treatment time was 46 days
(range 40-62). Response was assessed in 66 pts (94%).
In according to the RECIST criteria, 60% of pts achie-
ved a complete response (CR), 21% a partial response,
10% experienced a progression disease, 1% showed
stable disease. 15/41 pts with CR had a progressive
disease: 7 locoregional recurrences (4/7 underwent sal-
vage surgery/radiotherapy), 8 distant recurrences. At
the time of data analysis (May 2019), 21/70 were alive
and with no evidence of disease. For all pts, the median
OS was 5.5 years and the 3-years OS resulted 61%. The
3-years OS were 54.5% in oropharynx and
hypopharynx, 75% oral cavity, 77% larynx, and 100%
nasopharynx (Figure 1). The 3-years survival were
90%, 43%, 61% and 40% for stage I-II, III, IVa and
IVb, respectively. Actuarial 3-years PFS was 41%,
median PFS was 2.2 years. Meanwhile, 3 years Local
Recurrence-PFS resulted 67%. No significant differen-
ces between the subgroups of pts were found; the pri-
mary cancer site and overall treatment time (more than
10 days over 40 days scheduled) do not correlate with
OS and PFS.
Conclusions: In our analysis, moderate hypofractio-
nated SIB-IMRT for locally advanced HNSCC not
selected pts with or without chemotherapy produced
good results in term of response rate, PFS and OS.
CO068
CLINICAL OUTCOME IN LOCALLY ADVANCED
HEAD AND NECK CANCER PATIENTS TREATED
WITH MODERATE HYPOFRACTIONATED SIB-IMRT
F. Sanna , F. Cabras, A. Carai, S. Marogna, A.R. Musu,
E. Orefici, G. Piredda, P.L. Pittau, C. Sini, M. Urpis,
S. Campoccia
Radioterapia Oncologica Ospedale San Francesco
Nuoro, Italy
Aims: To retrospectively evaluate the clinical out-
come in patients (pts) treated curatively with a modera-
te hypofractionated regime for locally advanced head
and neck squamous cell carcinoma (HNSCC).
Methods: From 2011 to 2017, 70 pts were treated Figure 1.

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

had a negative impact on OS (P = 0,0011). This finding


was confirmed on multivariate analysis (P =0,0262)
CO069

(Figure 1)
Conclusions: Different RT techniques had no
COMPARISON OF 3D-CONFORMAL RADIOTHE-

impact on patterns of failure and outcome in LA-OSCC


RAPY (3DCRT) VERSUS SIB-IMRT ON PATTERN

patients. RT interruption remains a crucial prognostica-


OF FAILURE IN PATIENTS AFFECTED BY LOCAL-

tor in this setting.


LY ADVANCED ORAL CAVITY SQUAMOUS CELL
CARCINOMA (LA-OCSCC)
C. Bellini, M.A. Teriaca, G. Caramia, G. Stocchi,
C. Ciabatti, L.P. Ciccone, C. Becherini, I. Desideri,
P. Bonomo, L. Livi
CO070

Radioterapia Oncologica AOU Careggi, Università


A MONO-INSTITUTIONAL ANALYSIS OF
degli Studi di Firenze, Italy
COMBINED MODALITY TREATMENT FOR

Aims: The main treatment modalities for LA-


OESOPHAGEAL CANCER
S. Martini1, GC. Iorio1, F. Arcadipane2, G. Catalano3,
OCSCC are surgery and radio(chemo)therapy. Loco- E. Mazza3, P. Rubiolo1, P. Silvetti1, C. Fiandra1,
regional relapse represent the predominant pattern of R. Ragona1, U. Ricardi1, P. Franco1
failure in this setting. The aim of our study was to 1Department of Oncology, Radiation Oncology,
analyze the impact different RT techniques on pattern of
University of Turin; 2Department of Oncology,
failure and outcome.
Radiation Oncology, AOU Citta' della Salute e della
Methods: We performed a retrospective cohort
Scienza, Turin; 3Department of Surgery, General
analysis of consecutive patients treated at our institution
Surgery 2U and Liver Transplantation Center,
for LA-OSCC between March 2010 and January 2018
University of Turin, AOU Citta’ della Salute e della
with 3DCRT vs IMRT-SIB technique with adjuvant Scienza, Turin, Italy
intent with or without chemotherapy. By definitions,
3DCRT consisted of sequential shrinking field techni- Aims: To evaluate clinical outcomes, toxicity and
que (60-66Gy to high-risk CTV and 50Gy to low-risk postoperative complications of a consecutive series of
CTV) whereas in IMRT-SIB cohort low-risk CTV was patients affected with oesophageal cancer (both squa-
irradiated with 1,6-1,8Gy dose per fraction. mous cell - SCC and adenocarcinoma – ADK histology)
treated with trimodality strategy (TM).
Methods: We describe a retrospective cohort of 53
patients who received multimodality treatment at our
Institute (2014-2019). Radiotherapy (RT) was delivered
employing volumetric-modulated arc therapy (VMAT).
The more common RT schedules used were 41.4 Gy/23
fractions(fr) and 45 Gy/25 fr in ADKs and in SCCs,
respectively. The protocol contemplated RT with con-
current chemotherapy (CT, mainly, Carboplatin/
Paclitaxel and Cisplatin/5-fluorouracil in ADKs and in
SCCs, respectively) and subsequently surgery.
Results: Detailed patients, tumor, treatment charac-
teristics regarding both treatment volumes and organs at
risk, toxicity profile and grade of postoperative compli-
cations are provided in Table 1. In ADK cohort (25
patients), tumors were mostly located in distal esopha-
gus (22.7%) and gastroesophageal junction (22.7%).
Middle (22.6%) and lower thoracic (20.7%) esophageal
location were more common in SCC group. The most
frequent stage at diagnosis was cT3(90%), cN2(48%) in
Figure 1.

Results: A total of 94 patients were included in the ADK group and cT3(89.2%), cN1(64.2%) in SCC
study (48 M, 46 F). Median age was 63,1 y. 62,8% of cohort. Maximum acute RT-CT toxicities were lympho-
the study population had PS 0. 22,3% of patients had penia≥G3(83%), leukopenia≥G3 (22.5%), anorexia-
stage III, 67% had stage IVa and 3% had stage IVb. G3(22.7%), esophagitis-G3(13.2%) and asthenia-
Primary tumour location was mobile tongue. 37 G3(13.2%). Thirty-seven patients underwent surgery.
patients were treated with 3DCRT and 57 were treated Disease progression was the most frequent reason to
with IMRT-SIB. Median interval between surgery and deem patients as unoperable (21%). Subtotal esopha-
the start of adjuvant treatment was 77 days. The median gectomy was the most frequent surgical procedure
number of days of interruption of RT treatment was 3.2. performed (81%). Eighteen patients reported acute sur-
At a median F-UP of 2,5 years actuarial DFS and OS gical complications and in 6 patients Clavien–
were 10.7 and 29.7 months respectively. In terms of pat- Dindo≥G3 were observed. Globally, 22 patients had
tern of failure, no difference between the two groups grade 1 and grade 2 pathological tumor regression
was observed. On univariate analysis, RT interruption (TRG) according to Mandard classification (18.9% in

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ADKs and 40.5% in SCCs). A pN0-pN1 stage was


reported among 32 patients (40.5% in ADKs and 46%
in SCCs). Two-year overall survival was 48% in SCC
group and 40% in ADK cohort, while 2-year cancer-
specific survival was 58% and 42% in SCCs and in
ADKs, respectively. For details regarding treatment-
response and clinical outcomes see Figure 1.
Conclusions: Our clinical results support the TM
approach, employing VMAT as RT technique, in
oesophageal cancer patients. A mild toxicity profile was
reported. Short-term oncological outcomes are in line
with those reported in the literature.

Table 1. Patients, tumor, treatment characteristics, radiotherapy toxicity profile and


grade of postoperative complicationsand treatment response.

Figure 1. Clinical outcomes.

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Methods: From January 2011 to May 2018 we


retrospectively analyzed 111 patients (pts) with LACC
CO071

FIGO IB2-IVa. Pts treatments schedule were CT and


EBRT with IMRT or Tomotherapy, followed by BRT.
EVIDENCE FOR AN IMPROVED THERAPEUTIC

BRT treatment was planned with MRI or CT scan.


INDEX WITH IMAGE GUIDED ADAPTIVE

Toxicity was scored according to CTCAE v4.0. Our pri-


RADIOTHERAPY PLUS BRACHYTHERAPY IN

mary end point is to evaluate clinical acute and late


LOCALLY ADVANCED CERVICAL CANCER
I. Chiola1, E. Olivetta1, L. Carmisciano3, L .Belgioia1,2,
S. Callegari1, G. Polizzi1, V. Marullo1, A. Pastorino1, toxicity, secondary endpoint is overall survival.
C. Satragno1, E. Tornari1, D. Tramontano1, L. Trapani1, Results: Pts treatments schedule were the fol-
F. Giannelli 2, M. Marcenaro2, R.Corvò1,2 lowing: concomitant CT with (only 16 pts didn’t recei-
1DISSAL Università degli studi di Genova; 2U.O.C.
ve CT because of age or comorbidity) and EBRT with
IMRT or Tomotherapy with median total dose 45 Gy
Radioterapia Oncologica Policlinico San Martino (range 42-50.4) on pelvic +/- median dose 57.5 Gy
Genova; 3Department of Health Sciences, University of (range 16-61.1) on node if there were positive, followed
Genoa, Italy by BRT (median dose 28 Gy (range 28-30) in 4-5 frac-
Aims: Traditional standard treatment for locally tion. Median follow up is 2,5 years (IQR 1,4-3,7 years),
advanced cervical cancer (LACC) includes external and OS is 87% (95% CI 80-95) at 2,5 yy.
beam radiotherapy (EBRT) with concomitant che- Conclusions: As reported in literature we experien-
motherapy (CT) followed by intracavitary brachythe- ced that introduction of image guided adaptive
rapy (BRT). Introduction of image guided adaptive radiotherapy has increased the therapeutic index
radiotherapy has improved disease outcome and redu- (improved disease outcome and reduced toxicity) in
ced toxicity in LACC. Aim of this study is to evaluate LACC. In our experience symptoms score registered
clinical outcome of chemoradiotherapy and acute and were low and the major of pts considered acceptable
late toxicity in patients with LACC treated with their QoL.
EBRT+/-CT follow by BRT. The majority of treatment
were planned using MRI for the best dose optimization
to the target and OARs at time of treatment.
CO072
ADJUVANT VOLUMETRIC MODULATED ARC THE-
RAPY (VMAT) COMPARED TO THREE DIMENSIO-
NAL CONFORMAL RADIATION THERAPY (3DCRT)
FOR NEWLY DIAGNOSED EXTREMITIES SOFT
TISSUE SARCOMA PATIENT. OUTCOME AND
TOXICITY EVALUATION
L. Di Brina1, P. Navarria1, G. D'Agostino1, I. Renna1,
A. Tozzi1, T. Comito1, C. Iftode1, F. De Rose1,
C. Franzese1, D. Franceschini1, M. Scorsetti2
1Humanitas Clinical and Reasearch Hospital,
Radiotherapy and Radiosurgery Department;
2Biomedical Sciences, Humanitas University, Rozzano

(MI), Italy
Introduction and Purposes: To assess the impact of
adjuvant volumetric modulated arc therapy (VMAT)
compared with three dimensional conformal radiation
therapy (3DCRT) in terms of toxicity and local control
in patients with soft tissue sarcoma (STS) of the extre-
mities treated with radical surgery and adjuvant
radiotherapy.
Materials and Methods: From 2004 to 2016, 109
patients were treated, initially using 3DCRT and subse-
quently with VMAT. Clinical outcome was evaluated
by contrast-enhanced MRI, thoracic and abdominal CT
3 months after treatment and then every 6 months.
Toxicity was evaluated with Common Terminology
Criteria for Adverse Events (CTCAE) scale version 4.3.
Results: The vast majority of patients had stage I-
III STS disease (95%), liposarcoma (57%) histology,
localized at the lower extremity (87%). Surgical resec-
tion was performed in all patients, followed by adjuvant
3DCRT in 38, and VMAT in 71. The median total dose
Figure 1.

was 66 Gy/33 fractions (range 60-70 Gy;25-35 frac-

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tions). More successful bone sparing was recorded Anterior rectocele was observed in 15 patients, mostly
using VMAT (p<0.01). Median follow-up was 68 in women (9 vs 6). A reduced or poor contraction or
months. The 2,5-year LC were 95.3%±0.02, and inhibition of the pubo-rectal muscle in DRE performed
87.4%±0.03 for the whole cohort, 92%±0.05, within 2 years was reported in the 73% whereas it resul-
82.9%±0.06 for 3DCRT, 97.1%±0.02, 89.6%±0.04 for ted of 44% in DRE performed after 2 years (8 patients
VMAT (p=0.2). On univariate and multivariate analysis for each group). Regarding functional assessment, 5
the factors recorded as conditioning LC were the status (45%) and 7 (39%) patients showed incontinence at rest
of the surgical resection margins and the total dose deli- at DRE performed within or after 2 years, respectively.
vered. Overall, MSKCC score overestimated functional asses-
Conclusions: The availability of modern RT techni- sments in 5 (17%) patients. Table 1 reported DRE cha-
que permits a better conformity on the target with maxi- racteristics and the MSKCC score for each patient.
mum sparing of normal tissue and acceptable side Conclusions: Despite the small number of analysed
effects. Our data underline that VMAT is a safe and fea- patients and the dose intensification schedule, sphincter
sible treatment with limited rate of toxicity, compared dysfunctions rate was in line with literature. DRE resul-
to 3DCRT. Results on local control of VMAT are ted an important tool to evaluate anorectal function,
encouraging. giving information regarding not only sphincter
morphology but also functionality. It resulted useful to
evaluate incontinence during Valsalva, completing a
qualitative evaluation of the MSKCC score. For an
CO073
accurate evaluation both DRE and MSKCC could be
considered.
ABSTRACT WITHDRAWN

CO074 Table 1.
DEFECOGRAPHY FOR ANAL SPHINCTER FUNC-
TION EVALUATION IN RECTAL CANCER PATIENTS
TREATED WITH PELVIC RADIOTHERAPY
C. Rosa1, B Seccia2, A. Delli Pizzi2, R. Cianci2,
R Basilico2, M. Taraborrelli1, M. Di Tommaso1,
L. Caravatta1, D. Genovesi1
1U.O.C. Radioterapia Oncologica, Ospedale
Clinicizzato SS Annunziata, Università G. D’Annunzio,
Chiet; 2Dipartimento di Radiologia, Ospedale
Clinicizzato SS Annunziata, Università G. D’Annunzio,
Chieti, Italy
Aims: Locally advanced rectal cancer patients trea-
ted with neoadjuvant chemoradiotherapy (CRT) and
sphincter saving surgery could suffer from sphincter
function disorders when recanalised. Defecography
(DRE) evaluates the transport of a semi-solid barium
column to outside during a simulated defecation, inve-
stigating the two component of this process, both ana-
tomically and functionally. The aim of this study was to
evaluate the sphincter functionality with DRE.
Methods: Twenty-nine locally advanced rectal can-
cer patients (M:W=18:11) underwent neoadjuvant dose
CO075

intensification treatment up to 5500 cGy (220 cGy/die) ADJUVANT INTENSITY-MODULATED HYPOFRAC-


and sphincter saving surgery. DRE was performed eva-
luating the characteristics of contraction or inhibition of
TIONATED IMAGE-GUIDED RADIOTHERAPY

the pubo-rectal muscle and the type of incontinence (at


(IGRT) CONCOMITANT TO CHEMOTHERAPY IN

rest/during Valsalva). The Memorial Sloan Kettering


BILIARY TRACT CARCINOMA
N. Slim, R. Tummineri, P. Passoni, A. Fasolo,
Cancer Center (MSKCC) Score was used to evaluate A.M. Deli, L. Aldrighetti, N. Di Muzio
the number of evacuations per day, including inconti- San Raffaele Scientific Institute, Milano, Italy
nence. A comparison of both methods was reported.
Results: All patients completed the prescribed treat- Background/Aims: Adjuvant (adj) radiotherapy
ment and underwent anterior rectal resection with com- (RT)/chemotherapy (ChT) is controversial in patients
plete pathological response rate of 51%. With a median (pts) with bile duct carcinoma (ca) but suggested in R1,
follow-up of 3.4 years, local control was recorded in all lymph nodes (LNs) positive or stage ≥ T2. We previou-
patients, with distant metastases reported in 6 (21%). sly tested Hypo-IGRT in pts with locally advanced pan-
Twenty-nine patients underwent DRE: 11 patients creatic ca (Int J Rad Onc Biol Ph, Vol. 87, 2013). We
within 2 years, 18 after 2 years from the end of CRT. report our experience using the same RT schedule in adj

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setting in biliary tract ca. patients treated with chemoradiation (CRT), employing
Methods: pts with intra, extra-epatic or gallbaldder a tailored IMRT approach in order to spare hematopoie-
ca were treated. Simulation consisted in contrast-enhan- tic bone marrow (BM) identified with (18F)-FDG posi-
ced computed tomography (c-e-CT) or FDG CTPET or tron emission tomography (18FDG-PET)
4D c-e-CT, CTV consisted in surgical bed and regional Methods: A one-armed two-stage Simon’s design
LNs considering tumor site. PTV was defined adding was selected to test the hypothesis that BM sparing
standard margins to CTV or 5 mm in pts who approach would improve by 20% the rate of G0–G1 (vs
underwent 4D c-e-CT. Prescription dose was 40- 44.25 G2-G3) HT from 27% of RTOG 0529 historical data to
Gy (40-50 Gy) in 15 fr with SIB up to 50 Gy to R1 or 47% (α=0.05 and the β=0.20). At the first stage, among
positive CTPET sites respecting dose constraints to 21 enrolled patients, at least 9 should have been scored
OAR delivered with VMAT or tomotherapy concomi- as G0– G1 acute toxicity to further proceed with the
tant to capecitabine (cape). trial. At the second stage, another 18 patients will be
Results: From 05/2009 to 04/2018, 40 pts (25 M; 15 accrued for an overall sample size of 39 patients. The
F) were treated. Median age: 69 years (45-83). Twenty- first step was conducted in 21 patients eligible for con-
one pts (52.5%) had Klatskin tumor, 11 pts (27.5%) current CRT following Nigro protocol, dose and con-
common or distal bile duct ca, 5 pts (12.5%) intrahepa- straints of RTOG 0529 trial. We employed 18FDG-PET
tic ca and 3 pts (7.5%) gallbladder ca. After surgery 28 to identify active BM within pelvic structures (active
pts (70%) were R1, 12 pts (30%) were R0 (3: N+, 4: PBM) detached in 3 subsites: active iliac bone marrow
pT3N+, 2: pT4, 1: hepatic hilus infiltration, 2: after sur- (IBM), active lumbosacral bone marrow (LSBM), acti-
gery for local relapse). Four pts were previously treated ve lower pelvis bone marrow (LPBM). Active BM was
with neoadj ChT (3: GEM+CDDP, 1: cape). Fourteen defined according to the segmentation identifying
pts received adj ChT (7: CDDP+GEM, 2: GEMOX, 2: regions within the pelvis with higher SUV than the
PEXG, 1: GEM, 1: cape, 1: CBDCA+ VP16). Twenty- mean SUV for that bony region, for each patient. Dose
seven pts (67.5%) received concomitant ChT. constraints were: V10< 90% and V20<75% for active
Simulation was performed with c-e-CT and CTPET in PBM, V40< 41% and mean dose <32 Gy for active
16 pts (40%), with 4D c-e CT in 6 pts (15%) and with LSBM. Acute HT events and non-hematologic toxicity
c-e-CT in 18 pts (45%). Twelve pts (75%) were PET were recorded.
positive. Twenty-four pts (60%) were treated with Results: From December 2017 to March 2019, 21
tomotherapy and 16 (40%) with VMAT. All pts were patients met the eligibility criteria and were enrolled
evaluable for acute toxicity, it was G1-G2: 3 pts (7.5%) onto the protocol. Six patients (28%) had stage II disea-
diarrhea, 19 (47.5%) nausea/vomiting, 8 (20%) abdo- se and 15 (72%) stage III. The median age was 64 years.
minal pain, 3 (7.5%) cholangitis, 1 (2.5%) gastric ulcer. Six out of 22 patients were male. Four patients expe-
Only 2 pts (5%) had G3 late toxicity (gastric ulcer and rienced grade 3–4 HT,19% versus 58% of historical
stenotic fibrosis). Responses were evaluated in 39 pts (1 results; 17 patients had ≤G2 HT and 9 patients ≤G1 HT.
lost): 22 pts (56%) had PD (7 distant, 6 local, 9 local None of the patients showed grade 4 thrombocytopenia.
and distant). Median TTLP and TTDP from end of RT Figure 1 shows hematological values trends over the 8
were 12.5 and 13.7 months, respectively. At a median weeks from the start of CRT. A total of 55% of patients
follow up of 31 months (11.8- 110.6 m) 50% of pts were had G0-G1 gastroenteric toxicity and 73% had urogeni-
alive; 1 and 3 years OS were 72% and 36%, respecti- tal toxicity <G2 (27% G2-G3), while G2-G3 acute skin
toxicity was experienced by 75% of patients.
vely.
Conclusion: PET-guided BM sparing IMRT was
Conclusions: Adjuvant Hypo-IGRT concomitant to
able to reduce acute HT in anal cancer patients treated
capecitabine in pts with biliary tract carcinoma is feasi-
with CRT. These results prompted us to continue with
ble with a good toxicity profile and promising outcome.
the second part of this prospective phase II trial.

CO076
BONE-MARROW SPARING IMRT FOR ANAL CAN-
CER PATIENTS: A PROSPETICVE PHASE II TRIAL
F. Arcadipane1, P. Silvetti2, C. Fiandra3, E. Gallio3,
F. Giglioli3, S. Martini2, G.C. Iorio2, F. Olivero2,
A. Gastino2, V. De Luca2, U. Ricardi2, P. Franco2
1Department of Oncology, Radiation Oncology, AOU

Citta' della Salute e della Scienza; 2Department of


Oncology, Radiation Oncology, University of Turin;
3Department of Medical Physics, Radiation Oncology,

University of Turin; 4Department of Medical Physics,


Radiation Oncology, AOU Citta' della Salute e della
Scienza, Turin, Italy
Aims: This study was aimed at decreasing the acute
Figure 1.

hematologic toxicity (HT) profile in anal cancer

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By maintaining, during the inverse planning process,


the doses to the scalp lower than the dosimetric thre-
CO077

sholds that were identified, reduction of the risk of hair


loss may occur. Furthermore, these data may assist
DOSIMETRIC PREDICTORS OF ACUTE AND

radiation oncologists to predict the risk of alopecia


CHRONIC ALOPECIA IN BRAIN CANCER

during patient counselling.


PATIENTS TREATED WITH VOLUMETRIC
MODULATED ARC RADIOTHERAPY (VMAT)
V. Salvestrini1, S. Scoccianti1, G. Simontacchi1,
M. Perna1, F. Terziani1, R. Grassi1, M. Mariotti1,
D. Dei1, B. Guerrieri1, L.P. Ciccone1, D. Greto1,
M. Mangoni1, P. Bonomo1, C. Talamonti2,
CO078

A. Compagnucci2, S. Pallotta2 L. Livi1 FINAL RESULTS OF A PHASE I STUDY ON ACCE-


1Radiation Oncology Unit, Azienda Ospedaliera LERATED RADIOTHERAPY WITH SIB VMAT TECH-
Universitaria Careggi, University of Florence; NIQUE AND CONCOMITANT TEMOZOLOMIDE IN
2Department of Experimental and Clinical Biomedical

Sciences Mario Serio, Medical Physics Unit, Azienda


GLIOBLASTOMA PATIENTS (ISIDE-BT-2)
M. Ferro1, A. Ianiro2, G. Macchia1, A. Re1, V. Picardi1,
Ospedaliera Universitaria Careggi, University of S. Cilla2, M. Ferro1, M. Boccardi1, C. Romano2,
Florence, Italy S. Cammelli3, M. Buwenge3, S. Bisello3, G. Giglio4,
S. Mignogna5, P. Farina5, E. Cucci6, C. Pozzo5,
Aims: Radiation-induced hair loss is a side effect of V. Valentini7, A.G. Morganti3, F. Deodato1
relevant importance, given the huge psychological 1Fondazione Giovanni Paolo II, UO di Radioterapia,
impact of alopecia and its negative effects on patient’s
quality of life. This work aims to define the dosimetric Università Cattolica del Sacro Cuore, Campobasso;
2Fondazione Giovanni Paolo II, UO di Fisica Sanitaria,
parameters that correlate with temporary and permanent
hair loss following a radiation treatment for brain can- Università Cattolica del Sacro Cuore, Campobasso;
3Department of Experimental, Diagnostic and Specialty
cer in patients treated with conventionally fractionated
VMAT for brain tumors. Analysis of time to recovery Medicine - DIMES, University of Bologna, S. Orsola-
and definition of factors impacting on recover probabi- Malpighi Hospital, Bologna; 4UO di Oncologia Medica,
lity are described. PO Cardarelli Campobasso; 5Fondazione Giovanni
Methods: Patients treated for primary brain tumor at Paolo II, UO di Oncologia Medica, Università Cattolica
our Institute with a conventionally fractionated VMAT del Sacro Cuore, Campobasso; 6Fondazione Giovanni
were included. Factors that may have an impact on alo- Paolo II, UO di Radiologia, Università Cattolica del
pecia such as age, smoking history, use of antiepileptic Sacro Cuore, Campobasso; 7Fondazione Policlinico
Universitario A. Gemelli, IRCCS, UOC di Radioterapia,
drugs (AEDs) and chemotherapy were registered. Dose
Dipartimento di Scienze Radiologiche, Radioterapiche
received by 0.1 cc (D0.1cc), mean dose (Dmean), volu-
ed Ematologiche, Roma, Italy
mes receiving different doses (V16Gy, V20Gy, V25Gy,
V30Gy, V35Gy, V40Gy and V43Gy) were registered Aim. To determine the maximum tolerated dose
for the scalp. Alopecia was assessed according to (MTD) of Volumetric Modulated Arc Therapy (VMAT)
CTCAE version 4.0. Receiver operating characteristics with standard concurrent and sequential dose temozolo-
(ROC) curve analysis was used to identify parameters mide (TMZ) in patients with resected glioblastoma
associated with hair loss. multiforme.
Results: A total of 101 patients were included. At Methods. A Phase I clinical trial was performed.
the end of radiotherapy, 5 patients did not develop alo- Patients with histological proven glioblastoma
pecia (Dmean to the scalp 3.1 Gy). The scalp of the underwent VMAT dose escalation. VMAT was delive-
patients with G1 (n=11) and G2 (n=85) alopecia recei- red over 5 weeks with the simultaneous integrated boost
ved Dmean of 10.6 Gy and 11.8 Gy, respectively. At (SIB) technique to the two planning target volumes
ROC curve analysis, V16Gy ≥16.7 cc and V20Gy ≥5.2 (PTVs) defined by adding 5-mm margin to the respec-
cc were the strongest predictors of risk of acute alope- tive clinical target volumes (CTVs). CTV1 was the
cia. Trichological follow-up was available for 74 tumor bed + MR enhancing residual lesion with a 10-
patients: 65 patients (92.8%) completely recovered mm margin; CTV2 was CTV1 plus 20-mm isotropic
from alopecia. Median time to recovery was 5,9 margin.
months. The actuarial rate of hair regrowth was 98.1% VMAT was delivered in 25 fractions. Only the dose
at 18 months after the end of radiotherapy. At ROC for PTV1 was escalated while maintaining the same
curve analysis, V40Gy ≥5.4 cc and V43Gy ≥2.2 cc dose for PTV2 (45 Gy/1.8 Gy). Four PTV1 dose levels
were the strongest predictors of risk of chronic alope- were planned: Level 1 (77.5/3.1 Gy), Level 2 (80/3.2
cia. Kaplan Meier analysis and Cox regression showed Gy), Level 3 (82.5/3.3 Gy) and Level 4 (85/3.4 Gy).
that age, D0.1cc, Dmean, V30Gy, V35Gy, V40Gy and Patients were treated in cohorts of between three
V43Gy are related to recovery probability. and six per group using a Phase I study design. The
Conclusions: Volumes that receive relatively low recommended dose was exceeded if one of the three
doses (V16Gy and V20Gy) and those that receive rela- patients in a cohort experienced dose-limiting toxicity
tively high doses (V40Gy and V43Gy) are the strongest within 3 months from treatment. Concurrent and
predictors for acute and chronic hair loss, respectively. sequential TMZ chemotherapy was administered accor-

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ding to Stupp’s protocol. Two arc techniques were used Results: The coverage of the PTV is adequate with
to cover at least 95% of the target volume with the 95% all techniques in study allowing the average value of
isodose line. Dose-limiting toxicity (DLT) were defined V95% to be higher than 95% (V95% on PTV(%) 3D
as any treatment-related non-haematological adverse 94,1±1.9; IMRT 95.4±0.5; Tomotherapy
effects rated as Grade > 3 or any haematological toxi- 97.9±1.1;VMAT 95.2±0.7); however, Tomotherapy
city rated as > 4 by Radiation Therapy Oncology Group achieves the best results with an average of V95%
(RTOG) criteria. higher and with a more homogeneous dose distribution.
Results. Twenty-one consecutive glioblastoma The LAD is spared in an equivalent way with IMRT,
patients (male/female: 14/7; median age: 66 years) were VMAT and Tomotherapy, which obtain maximum and
treated. Dose to the PTV1: 10 patients 77.5 Gy; 9 avarage doses lower compared to 3DCRT (average and
patients, 80 Gy; 2 patients, 82.5 Gy,; 0 patients, 85 Gy. maximum doses(Gy): 3D 31.8±10.9, 51.4±1.8; IMRT
Median follow-up time was 10 months (range: 1-23.3 18.4±7.1, 39.7±6.5; Tomotherapy 23.5±10.4, 39.8±7.1;
months). Grade 1-2 treatment-related neurological and VMAT 20.4±9.1, 38±11). VMAT and Tomotherapy
cutaneous toxicities were registered (6 and 16 patients, obtain a V10 Gy of breast and lung right higher compa-
respectively). Two patients experienced DLT to dose of red to the other techniques (V10 breast and lung right
82.5 Gy (1 neurological toxicity grade 3, 1 haematolo- (%): 3D 4.1±5.7, 0.4±0.4; IMRT 1.2±1.4, 0.09±0.10;
gical grade 4). Tomotherapy 24.2±22.2, 1.7±1.4; VMAT 17±8,
Conclusions. DMT was reached at the dose level of 6.5±6.0).V20 of the ipsilateral lung is higher with
82.5 Gy. Volumetric Modulated Arc Therapy in patients 3DCRT (V20(%): 3D 26±8; IMRT 17.1±2.8;
with resected glioblastoma multiforme to a dose of 80 Tomotherapy 16.6±3.8; VMAT 21.8±4.9).
Gy in 25 fractions is well tolerated with TMZ at a daily Conclusions: Tomotherapy and VMAT allow better
dose of 75 mg/mq. sparing of LAD and PTV coverage, but at the price of a
higher V10 of contralateral organs.
CO079
CO080
A DOSIMETRIC COMPARISON OF LEFT-SIDED
BREAST RADIOTHERAPY TECHNIQUES TO TREAT ABSTRACT WITHDRAWN
CHEST WALL AND REGIONAL NODES AND
HEART SPARING
M. De Liguoro, N.L.V. Cernusco, M.G. Giri,
CO081

N. Simoni, R. Micera, A. Muraglia, M. Romano, LONG TERM RESULTS OF IG-IMRT IN PROSTATE


C. Cavedon, R. Mazzarotto CANCER PATIENTS WITH HIGH-RISK OF RELAPSE
AOUI Verona, Italy N.G. Di Muzio¹, C.L. Deantoni¹, C. Fiorino²,
C. Cozzarini¹, F. Zerbetto¹, P. Mangili², R. Tummineri¹,
Purpose: Radiation therapy is an essential compo- I. Dell'Oca¹, S. Broggi², M. Pasetti¹, A. Chiara¹,
nent in the treatment of breast cancer, reducing the risk M. Azizi¹, F. Borroni¹, L. Perna², R. Calandrino²,
of local recurrences after surgery in the absence of rele- A. Fodor¹
vant side effects. There is a potential risk of cardiotoxi- 1Department of Radiotherapy; 2Medical Physics, San
city in patients undergoing radiation therapy on the left Raffaele Scientific Institute, Milano, Italy
chest wall; this risk appears to be correlated with the
dose received by the anterior descending artery (LAD). Aims: To evaluate long-term results in patients (pts)
The aim of the study is to evaluate which radiation tech- with unfavourable intermediate-, high- and very high-
nique allows to obtain an adequate coverage of the PTV risk prostate cancer (PCa) (NCCN 2019 classification),
sparing as much as possible the organs at risk (OARs) treated with image guided- intensity modulated
with attention to the LAD. The techniques used are: radiotherapy (IG-IMRT).
conformal radiotherapy (3DCRT); IMRT; VMAT Methods: From 12/2006 to 05/2011, 100 PCa pts
radiotherapy; Helical Tomotherapy. were treated with radical moderately hypofractionated
Method: 10 treatment plans for patients with left IG-IMRT in a phase I-II prospective study. All pts
breast cancer undergone to mastectomy and reconstruc- underwent prophylactic pelvic irradiation to 51.8 Gy in
tion with expansor and adjuvant radiotherapy are cho- 28 fractions (EQD2 52.2 Gy, for α/β=1.5), with simul-
sen and replanned retrospectively using 4 different taneous integrated boost up to 65.5 Gy (EQD2 77.7 Gy)
treatment techniques. PTV includes left chest wall and to seminal vesicles and 74.2 Gy (EQD2 88 Gy) to pro-
regional lymph nodes. OARs include heart, LAD, state. Neoadjuvant and/or adjuvant androgen depriva-
lungs, right breast. LAD is delineated according to tion therapy (ADT) was prescribed in 90/100 pts for a
Lorenzei et al. For each treatment plan we evaluated: median of 28.9 months (3-120 months). All pts were
maximum dose and volume of PTV receiving at least treated with helical IMRT (Tomotherapy®, Accuray,
95%(V95%) of prescribed dose and average of V95%; Wisconsin) and daily IGRT (MVCT). Pts’ characteri-
average dose and maximum dose of LAD; average dose stics are reported in Table 1.
of the heart; volume of the left lung receiving 20Gy Results: Median follow up was 94 (23-215)
(V20); breast and right lung volume receiving months. Cumulative late gastro-intestinal (GI) toxicity
10Gy(V10). were: 13% G2 and 6% G3 (rectal bleeding), the latter

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requiring Argon Plasma Coagulation (APC). At the last irradiated with 6MV VMAT technique. Dose prescrip-
follow up none of the pts presented G3 GI toxicity. tion was 2.7Gy/fr to prostate and 2.3Gy/fr to seminal
Cumulative late genito-urinary (GU) toxicities were vescicles for 26 fractions. Patients underwent a daily
15% G2 and 13% G3-G4; 11 pts presented G3 urinary CBCT verification. Bladder and rectal volumes had
stenosis and in 7 the G3 toxicity was solved with ureth- been contoured on each CBCT and dose-volume histo-
rectomy, thus only 4% of pts presented G3 GU toxicity gram (DVH) for every single fraction had been genera-
at the last follow up. Two patients presented G4 events ted. The variables derived from DVH were as follows:
(1 urethrostomy, due to repeated urethrectomies, and 1 volume (VB), mean dose (DB) and % of volume recei-
cystectomy, due to hyperactive bladder). Thirty pts ving ≥ 65Gy (V65Gy) for the bladder [Pervez et al.
were dead at the last follow up, but only 5 due to PCa IJROBP 76 (1) 57-64 2010], volume (VR), mean dose
progression. Eleven pts experienced biochemical rela- (DR) and % receiving ≥ 35-55-61Gy (V35Gy, V55Gy,
pse, 1 of whom also with an intraprostatic relapse and 2 V61Gy) for the rectum (from Pollack et al. IJROBP 64
with bone metastases. Fifty-nine pts are alive and free (2) 518-526 2006, Peeters et al. IJROBP 64 (4) 1151-61
from biochemical progression. Median biochemical 2006 and our constraints). Variables distributions are
relapse-free survival (bRFS) and distant progression- described by mean and standard deviation. The presen-
free survival from the last day of RT were 91.2 and 93.5 ce of statistically significant differences in term of
months, respectively. mean variables doses between two groups was assessed
Conclusions: IG-IMRT in PCa pts with high-risk of by the Welch’s two sample t-test.
relapse allows dose escalation, with very good 8 year-
outcomes: 89% bRFS, 1% local relapse, 2% distant
relapse and 95% cancer specific survival. Rectal G3
Table 1.

toxicity was acceptable, and solved in all pts with APC.


Genito-urinary G3 toxicity was fair, limited by the pre-
sence of the urethra in the field, and solved in 7 out of
11 pts.

Table 1. Patients' characteristics.

Results: In the bladder DB was significantly higher


in TGGU than in CGGU (35.3Gy vs 27.2Gy, p-value
CO082 0.024); VB and V65Gy did not show statistically signi-
ficant differences between groups (p-value > 0.05)
although VB was lower while V65Gy higher for TGGU
TOXICITY ASSESSMENT AND CORRELATION

than CGGU [Table 1]. In the rectum VR, V35Gy and


WITH VOLUME EFFECTS AFTER RADIOTHERAPY
V61Gy were significantly increased in TGGU compared
FOR PROSTATE CANCER
P. Tabarelli de Fatis, M. Liotta, E. Abate, A. Malovini, to CGGU (p-value < 0.05), while no statistically signifi-
I. Meaglia, G.B. Ivaldi cant difference was observed in terms of DR and V55Gy
Istituti Clinici Scientifici Maugeri, Pavia, Italy between the two groups (p-value > 0.05) Table 1.
Aims: To identify dosimetric parameters derived Conclusions: different volume effects were found
from bladder and rectal dose distributions that correlate for various acute GU and late GI toxicity. These con-
with acute genitourinary (GU) and late gastrointestinal straints can be used to evaluate and reduce the risk of
(GI) toxicity in patients treated for prostate cancer who toxicity in patient treated for prostate cancer, as repor-
underwent daily IGRT with Cone Beam CT (CBCT). ted in literature.
Methods: A retrospective analysis to investigate
dosimetric predictors for acute GU and late GI toxicity,
scored with RTOG scale, has been performed on 28
patients at I.C.S. Maugeri (Pavia). 16 patients (toxicity
group TGGU) presented G1-G2-G3 GU toxicity during
treatment or within 3 months after RT, while 12 (control
group CGGU) did not report any toxicity. 15 patients
(toxicity group TGGI) presented G1-G2 GI toxicity
from 6 months after RT, while 13 (control group CGGI)
have not reported any disease. All the patients have
been simulated with full bladder and empty rectum and

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CO083 Table 1.
THE ADDING VALUE OF IMAGE-GUIDED VMAT ON
THE GASTROINTESTINAL AND GENITOURINARY
TOLERANCE IN THE TREATMENT OF PROSTATE
CANCER WITH A MODERATE HYPOFRACTIONA-
TED SCHEDULE
G. Grimaldi1, F. Rossi1, A. Chalaszczyk1, C. Sorce1,
I. Mihoci1, C. Bertoldo1, F. Vittorini2, P. Franzese3,
V. Ruggieri3, M. Di Staso3, E. Varrassi3,
F. Marampon4, R. Gimenez De Lorenzo2,
V. Tombolini4, C. Masciocchi1, G.L. Gravina1
1Division of Radiotherapy, Department of
Biotechnological and Applied Clinical Sciences,
University of L'Aquila; 2Division of Medical Physics,
San Salvatore Hospital, L’Aquila; 3Division of
Radiotherapy, San Salvatore Hospital, L’Aquila;
4Division of Radiotherapy, Department of Radiological,

Oncological and Pathological Sciences, Policlinico


Umberto I, Sapienza University of Rome, Italy
Aims: To compare the acute and 1-year post-RT GI
and GU toxicity of men undergoing curative hypofrac-
tionated-RT (HFRT) and treated by three-dimensional
conformal radiation therapy (3DCRT) or VMAT with
daily IGRT.
Methods: A retrospective cohort of 101 men with
low/intermediate risk prostate cancer (Pca) was selected
according to the NCCN criteria. Patients were treated
with a moderate HFRT schedule (60 Gy delivered in 20
daily fractions). A cone-beam based IGRT strategy was
adopted in all treated patients according to the latest cli-
nical indications (NCCN guidelines). Men were treated
with VMAT (n=31) or with 3DCRT (n=70). Acute toxi-
city was assessed during treatment and at 2 and 4 weeks
after the end of radiotherapy and every 12 weeks the-
reafter . Late toxicity, was analyzed 12 months after RT
completion. The GI and GU toxicities were rated accor-
ding to the Radiation Therapy Oncology Group
(RTOG) scale for early and late side effects. Differences
in the incidence of toxicities between the two groups
were evaluated by the Fisher’s exact test. A p-value
lower than 0.05 was considered statistically significant.
Results: Two weeks after RT a lower rate of Grade
2 or higher acute toxicity was observed in the group of Conclusions: Men undergoing HFRT with image-
men treated by VMAT. Grade 2 or higher GI and GU guided VMAT experienced a significantly lower acute
toxicity was observed in 41.4 % vs. 9.7% (p=0.001) and GI and GU toxicity with respect to men treated by
in 40% vs. 6.5% (p=0.0007) of men treated by 3DCRT 3DCRT. VMAT did not provide advantages on 1-year
or VMAT, respectively. One month after RT, the redu-
GI toxicity while provided a trend toward significant
ced toxicity observed in the study group treated with
difference in the rate of late GU toxicity. Longer fol-
VMAT was confirmed. The incidence of Grade 2 or
higher GI and GU toxicity was 28.6% and 20% after low-up and increased sample size will provide more
3DCRT and 9.7% and 3.2% after VMAT (GI toxicity: definitive evidence concerning this important topic.
p=0.04; GU toxicity: p=0.03). At 12 months after RT,
G2 or higher late GI toxicity was comparable between
3DCRT (4/70; 5,7%) and VMAT (2/31; 6,4%) (p=1.0)
while a trend toward significant difference in the rate of
late GU toxicity was observed between VMAT (29/2;
6,4%) and 3DCRT (54/16; 22,8%) (p=0.053).

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CO084 CO085
PRELIMINARY RESULTS OF HYPOFRACTIONATED HYPOFRACTIONATED WHOLE BREAST IRRADIA-
POST-MASTECTOMY RADIOTHERAPY (PMRT-HF): TION AND SIMULTANEOUS INTEGRATED BOOST
DOSIMETRY, LOCO-REGIONAL CONTROL AND IN LARGE-BREASTED PATIENTS: LONG-TERM
TOXICITY TOXICITY AND COSMESIS OF A PROSPECTIVE
F. Pati1, AL Vasconcelos2,3, J. Hernandez2,3, SERIES
A. Soares2, A. Martins2, F. Cardoso3, C. Greco2,4 F. De Rose1, A. Fogliata1, D. Franceschini1, C. Iftode1,
1Unità Operativa Complessa di Diagnostica per G.R. D’Agostino1, T. Comito1, C. Franzese1, A. Tozzi1,
Immagini e Radioterapia, AOU Federico II; 2Radiation L. Di Brina1, E. Clerici1, P. Navarria1, W. Gatzemeier3,
Oncology Department – CCU, Champalimaud A. Testori3, C. Tinterri3, F. Lobefalo1, S. Tomatis1,
Foundation; 3Head of the Breast Unit – CCU, M. Scorsetti1,2
1Radiotherapy and Radiosurgery Department,
Champalimaud Foundation; 4Head of the Radiation
Oncology Department – CCU, Champalimaud Humanitas Clinical and Research Hospital;
2Department of Biomedical Sciences, Humanitas
Foundation
University; 3Department of Breast Surgery, Humanitas
Aims: Post-mastectomy radiation therapy (PMRT) Clinical and Research Hospital, Rozzano, (MI), Italy
with conventional fractionation is typically delivered in
5 to 6 weeks. Data supporting hypofractionated PMRT Purpose: To evaluate the impact of breast size on
is limited. This study aims to determine whether a short long-term toxicity and cosmesis in breast cancer
course of hypofractionated schedule in 15-16 fractions patients treated with hypofractionation and simulta-
is safe and effective. neous integrated boost using volumetric modulated arc
Methods and Materials: Eligible patients with stage therapy (VMAT).
IA to IIIB primary breast cancer received hypofractio- Materials and Methods: Three cohorts were identi-
nated PMRT with fixed beam IMRT or VMAT techni- fied: small-breasted patients (<600 cc), medium-brea-
que to the chest wall (CW) with or without loco-regio- sted patients (between 600 and 1000 cc) and large-brea-
nal lymph nodes. Prescription dose was 40.5 in 15 and sted patients (>1000 cc), according to the 33^ percentile
42.5Gy in 16 fractions daily, with an optional simulta- in our database. Two groups were analyzed: small-
neous integrated boost (SIB) of 3.2 Gy /fraction to medium breasted patients (<1000 cc, 596 patients) and
48Gy. The primary endpoint was loco-regional recur- large breasted patients (>1000 cc, 256 patients). All
patients undergoing breast-conserving surgery were
rence free survival (LRFS); secondary endpoints were
treated with hypofractionated VMAT to the whole brea-
acute and late skin toxicity, overall survival (OS) and
st (40.5 Gy in 15 fractions) and concomitant boost dose
disease free survival (DFS).
to the tumor bed (48 Gy in 15 fractions). Skin toxicity
Results: Between 2012 and 2018, 83 patients with a
and cosmetic data were analyzed as acute and late (at 2,
median age of 51 years old were retrospectively analy-
3, 4 and 5 years follow-up). Multivariate logistic regres-
sed. All patients received adjuvant hypofractionated sion analyzed, as covariates, the variables with p<0.10
PMRT: 90,3% with 40,5Gy/15 frs /2.7Gy per fraction on univariate analysis. P values <0.05 were considered
and 9,5% with 42,56Gy/16 frs /2,66Gy. SIB with significant.
3.2Gy/fr was adopted in only 5 cases. Bolus 5 mm was Results: From August 2010 to March 2017, a total
used in 33 patients (40%). CTV- PTV volumes included cohort of 1160 patients have been treated with VMAT
CW in 8 patients (9,5%) and CW + regional LN in 75 and SIB in 3 weeks treatment. Of those, 852 patients
patients (90,5%). At a median follow-up of 34 months, had at least 2 year follow-up, and were included in the
2 patients developed loco-regional recurrence (locally, analysis. Breast size was highly significant predictor for
one in the scar and one in-field regional lymph node). acute grade 2 or greater skin toxicity (12.9% vs 20,7%;
10 patients developed distant metastatic disease, inclu- p=0.004). Late skin toxicity was significant for breast
ding the 2 patients with loco-regional relapses. LRFS size from 2 to 5 year FU (4.7% had grade 1 or more late
and distant metastasis free survival were 98.6% (95% skin toxicity in the group <1000 cc at 5 years, respecti-
CI 0.89 – 1.00) and 89.0% (95% CI 0.89 – 1.00), vely, to compare with 15.9% of the large breast group,
respectively. The hypofractionated regimen was well p=0.001). No Grade 3 of late skin toxicity was recorded
tolerated with 24.1% (20/83) G2 and 3.6% (3/83) acute in both cohorts. Regarding breast pain, the breast size
skin toxicity. So far no cases of G3 late skin toxicity kept significance in multivariate analysis from 2 to 4
have been observed. The 3-year actuarial OS and DFS year FU. For cosmetic outcome, the multivariate analy-
were 94.3% (95% CI 0.88 – 1.00) and 89.0 (95% CI sis confirmed the significance only of the breast size at
0.88 – 0.90), respectively. 2 years. No dosimetric or size related parameters were
Conclusions: Hypofractionated PMRT is well tole- significant for cosmesis nor breast pain at 5 year FU.
rated. Median follow-up in is still insufficient to assess Conclusions: Although increasing breast size leads
long-term loco-regional control and late toxicity. Our to increased maximum skin dose, the incidence of ove-
experience suggests high local control rates and toxicity rall skin toxicity, acute and late, was comparable to that
outcomes aligned with those already reported in litera- reported in the literature. At 5 years of follow up we did
ture with longer follow-up. not record significant differences in terms of cosmesis

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or breast pain between large and small-medium brea- que used and aimed to specific end-points. Modern
sted patients. These data suggest that hypofractionated TPSs should promote, even more, the use of either
radiation therapy using VMAT is a viable therapeutic radiobiological DVHs or algorithm optimization and
modality in large-breasted patients. gEUD metric, especially in the era of hypofractiona-
tion.

CO086
PREDICTIVE PARAMETERS FOR LONG-TERM
CARDIAC MORTALITY EXCESS RELATED TO
LEFT-SIDED BREAST RADIOTHERAPY
N. Pasinetti, F. Rottoli, V. Morandini, S. Berlinghieri,
E. Castrezzati, S. Pedretti, L. Spiazzi, L. Grimaldi
Servizio di Radioterapia - ASST Valcamonica - Esine
(Bs), Università degli Studi di Brescia, Italy
Aims: The risk of long-term secondary cardiac
effects in left breast radiation cannot be considered
negligible, mainly when it is may sum with those indu-
ced by chemotherapy schedules containing anthracycli-
nes and/or trastuzumab. Although a risk of cardiac
death <1% after breast RT is considered acceptable,
QUANTEC constraint V25Gy<10% is not sufficient to
limit the excess cardiac mortality risk for each patient
and for every RT schedule of tangential beams left
sided breast RT: evaluation of the heart-absorbed dose
is necessary. Aim of this work is to analyze the heart
dosimetric parameter of a group of patient for which
QUANTEC constraint is respected but cardiac morta-
lity probability results greater than 1%. Correlation
with further derived “predictive” dosimetric parameters
and cardiac mortality risk was then verified on a control
group of patients. Figure 1.
Methods: About 300 women, from 2013 to 2019,
underwent left sided breast tangential beams RT in our
department. The analysis showed that heart constraint
V25Gy<10% was respected in almost all patients. From
CO087

a qualitative analysis of the differential heart DVHs, RISK OF RADIATION-INDUCED SECONDARY


some high dose peaks emerged, then a direct calculation
of long term cardiac mortality risk was performed
LUNG CANCER AND ISCHEMIC HEART DISEASE

applying the relative seriality model (α/β=3Gy, s=1,


AFTER THE INTERNAL MAMMARY CHAIN IRRA-

D50=52.4Gy, g=1.28). For each heart absorbed dose


DIATION IN LEFT BREAST CANCER: COMPARATI-

distribution the EQD2 was used and the gEUDs were


VE ANALYSIS BETWEEN IMRT AND 3DCRT
V. Figlia1, S. Corradini2, S. Naccarato1, G. Sicignano1,
also evaluated (a=5.2). A. De Simone1, G. Napoli1, R. Mazzola1, F. Ricchetti1,
Results: In 25% of patients the probability of long- R. Ruggieri1, F. Alongi1,3
term cardiac mortality was found >1% despite 1Advanced Radiation Oncology Department, IRCCS
V25Gy<10% for heart volumes. The dosimetric con-
Sacro Cuore Don Calabria Hospital, Negrar-Verona,
straints V40Gy, D2%, and gEUD showed a good correla- Italy; 2Department of Radiation Oncology, LMU
tion (R=0.97, R=0.90 and R=1.00 respectively) with the University, Munich, Germany; 3University of Brescia,
risk of cardiac death. To keep the probability lower than Italy
1%, the cut off levels were determined by the simulta-
neous occurrence of the conditions: V40Gy <2% and Aims: To comparatively estimate the risks of radia-
D2% < 38Gy or gEUD < 23 Gy. On a control group of 50 tion-induced secondary lung cancer and ischemic heart
other patients (for whom V25Gy <10 was satisfied) these disease for different radiotherapy techniques (IMRT
parameters were tested: if simultaneously V40Gy and versus 3DCRT) in women with node-positive left-sided
D2% parameters or single gEUD were satisfied, the long breast cancer, candidates for breast and regional node
term cardiac mortality probability resulted <1%. The irradiation (RNI), including the internal mammary
parameter a in the gEUD was fixed at 5.1. chain (IMC).
Conclusions: Our additional “predictive” parame- Methods: For this risk modelling study, computed
ters, are a calculation and not an observation of morta- tomography datasets of ten women with node-positive
lity and are closely connected to the irradiation techni- left-sided breast cancer were used for IMC contouring

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and re-planning with a dose of 50Gy in 25 fractions. Radiotherapy and Oncology 111: 366–373.
Four different treatment plans were generated for each doi:10.1016/j.radonc.2014.05.004.
2. Darby, Sarah C, Marianne Ewertz, Paul McGale, Anna M
patient: for both techniques (3D-CRT and IMRT) two Bennet, Ulla Blom-Goldman, Dorthe Brønnum, Candace
treatment plans were created, based on the inclusion of Correa, et al. 2013. Risk of ischemic heart disease in women
IMC. We calculated estimates of excess relative risk after radiotherapy for breast cancer. The New England jour-
(ERR) and excess absolute risk,(EAR) for lung cancer nal of medicine 368: 987–98. doi:10.1056/NEJMoa1209825.
3. Budach W. , Bölke E. , Kammers K. , Gerber PA. , Nestle-
and major coronary events, as following: ERRlung= Krämling C. , Matuschek C. Adjuvant radiation therapy of
δGrantzau∙OEDlinear (δGrantzau=0.085Gy-1, regional lymph nodes in breast cancer - a meta-analysis of
Grantzau et al.1 with an excess relative risk of 8.5% per randomized trials- an update. Radiat Oncol. 2015 Dec
Gy of radiation-induced secondary lung cancer; 21;10:258. doi: 10.1186/s13014-015-0568-4.
OEDlinear=mean lung dose, MLD) and ERRheart=
δDarby∙ OEDlinear (OEDlinear=mean cardiac dose,
MCD; δDarby=0.074Gy-1 derived from dose-response
CO088
relationship reported by Darby et al.2). Statistical analy-
ses were conducted using Wilcoxon signed-rank tests to
LEFT SIDED BREAST CANCER PATIENTS AND

estimate statistical significance.


ADVANCED RADIATION THERAPY TECHNIQUES.

Results: The IMC irradiation increased significan-


A CARDIAC SPARING APPROACH
F. Cucciarelli1, S. Di Biase1, S. Costantini1,
tly the MCD and the ipsilateral MLD in both, 3DCRT M. Parisotto2, M. Valenti 2, L. Fabbietti1, F. Fenu1,
and IMRT plans (p=0.002), with a consequently signifi- M. Montisci1, L. Vicenzi1, M. Giacometti 2,
cant increase of the relative risk of secondary lung can- L. Reversi2, V.E. Morabito2, S. Maggi2, M. Cardinali1,
cer (64% vs 38%) and ischemic heart disease (41% vs G. Mantello1
27%). As compared to 3DCRT, the use of IMRT signifi- 1SOD Radioterapia, AOU Ospedali Riuniti di Ancona;
cantly reduced the MCD in IMC plans (p= 0.002) and 2SOD Fisica Sanitaria, AOU Ospedali Riuniti di
in plans not including the IMC (p=0.02). Similarly, the
MLD was significantly reduced in IMC plans (p=0.004) Ancona, Italy
and non-IMC plans (p=0.04), resulting in significant Aims: To improve target coverage and reduce dose
reduction of ERRlung in IMC plans (75% vs 58%, to heart and left anterior descending artery (LAD) in
p=0.002) and no-IMC plans (51% vs 44%, p=0.02). left breast cancer patients (pts) with comorbidities and
Higher ERR and 10-year EAR for major coronary unfavorable anatomy using volumetric modulated arc
events were showed for 3D-CRT as compared to IMRT therapy (VMAT) with or without deep inspiration
plans in boths, IMC-plans(64% vs 41%, p=0.002) and breath hold (DIBH).
no-IMC plans(38% vs 27%, p=0.02, Figure 1). Methods: Between July 2015 and April 2019 52
Conclusions: Despite IMC irradiation has been consecutive patients affected by left breast cancer with
shown to increase survival rates in women with nodal comorbidities and unfavorable anatomy underwent
positive breast cancer, Budach et al.3, the addition of radiotherapy (RT) with VMAT techniques. 29 pts recei-
IMC to RNI also increases heart and lung doses, resul- ved RT to whole breast in 15 fractions (total dose 40.05
ting in a significant increase in 10-year secondary lung Gy) and 23 pts to whole breast or chest wall plus regio-
cancer and ischemic heart disease risk. In this setting, nal lymph nodes in 25 fractions (total dose 50 Gy). A
the adoption of IMRT is advantageous when compared
sequential boost to the tumor bed of 10-16 Gy was
to 3DCRT.
performed, if indicated. In 6 cases DIBH technique was
performed. VMAT plans in free breathing (FB) were
generated using 3 arcs (180-220°), in order to reduce
the interplay effect due to dynamic delivery and brie-
fing motion, while VMAT plans in DIBH were obtained
using 6 partial arcs with a width of 12-15 degrees to
limit the time of delivery per arc; a virtual 10 mm bolus
helped extending the dose fluency outside the body to
compensate for small changes in shape and volume due
to respiration or edema. Most pts received anthracycli-
ne and taxanes regimen before RT, followed by trastu-
zumab. In all patients, echocardiography was perfor-
med before starting RT and after 1- and 6-months. Dose
constraints to heart were: Dmean ≤ 5 Gy, V5Gy ≤ 40%,
V25Gy ≤ 8% in FB and conventional fractionation
(CF); Dmean ≤ 4 Gy, V8Gy < 30%, D5% < 16 Gy in
FB and hypofractionation (HF); Dmean ≤ 3Gy, V25 ≤
5% in DIBH. Dose constraints to the LAD were Dmean
Figure 1.

References ≤ 20-25 Gy in FB, Dmean ≤ 15 Gy in DIBH.


Results: The treatment was well tolerated in all
1. Grantzau, Trine, Mette Skovhus Thomsen, Michael Væth,
and Jens Overgaard. 2014. Risk of second primary lung can- patients. Median V95% to breast/chest wall CTV was
cer in women after radiotherapy for breast cancer. 96% and median V95% to lymph nodes CTV was 98%,

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both in FB and in DIBH. In FB we obtained a heart Results: Of the 65 prospectively enrolled patients,
Dmean= 3 Gy in HF treatment and Dmean= 5 Gy in CF. 49 T2W-MRI sequences fulfilled the inclusion criteria.
LAD Dmean was 10.5 Gy and 16 Gy, respectively. In For each patient, 1058 radiomic features were identified
DIBH treatment we reported a heart V25=2% and a and then grouped in 30 clusters to reduce dimensiona-
mean LAD dose of 7 Gy. The 1- and 6-months echocar- lity. A logistic regression (machine learning) classifier
diographic control after RT completion showed unchan- was trained to predict clinical outcomes. Results are
ged cardiac functioning parameters. shown in Table 1. Radiomic signature for prediction of
Conclusions: The VMAT technique +/- DIBH is high Gleason score included only GLCM3 texture fea-
useful in the treatment of left breast cancer pts (espe- tures. Radiomic signature for prediction of cT2 stage as
cially with cardiac comorbidities and unfavorable ana- well as for 3/4 ECE score included first-order statistics
tomy) by ensuring an excellent target coverage and spa- intensity features. A GLCM3 texture feature was the
ring heart and LAD. Long-term follow-up data are nee- most predictive feature for 4/5 PIRADAS score, with
ded to assess late toxicity and clinical outcomes for this excellent predictive accuracy. Finally, radiomic signatu-
subset of patients. re for prediction of intermediate risk class included both
GLCM3 texture and first-order statistics intensity featu-
res, with good predictive accuracy.
CO089 Conclusions: MRI-based radiomics in PCa for the
prediction of tumour phenotype is a feasible and promi-
sing approach. It might lead to a semi-automated defi-
ASSOCIATION OF MRI-BASED RADIOMIC FEATU-

nition of tumour characteristics and thus reduce the


RES WITH PROGNOSTIC FACTORS IN PROSTATE
intra/inter-operator variability in the radiologic image
CANCER
G. Marvaso1, D. Ciardo1, S.G. Gugliandolo1, M. Pepa1, interpretation. We plan to increase the dataset dimensio-
S. Raimondi2, S. Volpe1,3, F. Botta4, L. Bianchini4, nality in order to strengthen the statistical power and to
G. Riva1,3, D. P. Rojas1, G. Petralia5, S. Alessi5, validate results.
P. Pricolo5, J.L. Isaakson1,6, R. Orecchia6,
M. Cremonesi4, M. Bellomi3,5, B.A. Jereczek-Fossa1,3
1Department of Radiation Oncology, IEO, Istituto
Table 1. Predictive accuracy of radiomic signature.*

Europeo di Oncologia IRCCS, Milan; 2Division of


Epidemiology and Biostatistics, IEO Istituto Europeo di
Oncologia IRCCS, Milan; 3Department of Oncology
and Hemato-oncology, Università degli Studi di Milano,
Milan; 4Unit of Medical Physics, IEO, Istituto Europeo
di Oncologia IRCCS, Milan; 5Division of Radiology, AUC=Area Under the receiving operator characteristic Curve;
IEO Istituto Europeo di Oncologia IRCCS, Milano; CI=Confidence Intervals;
6European School of Molecular Medicine (SEMM),
GLCM=GrayLevelCooccurenceMatrix;
Milan; 7Scientific Direction, IEO, Istituto Europeo di GLRLM=GrayLevelRunLengthMatrix;
Oncologia IRCCS, Milan, Italy GOH=GradientOrientHistogram;
ID=Intensity Direct.
Aims: To decode tumor phenotype in prostate can-
*obtained by unconditional logistic regression models with stepwise selection of the cluster
cer (PCa) using a radiomic approach based on multipa-
representative radiomic features for each outcome. ^95% CI obtained by the De Long
rametric magnetic resonance imaging (MRI).
method (ref). ° per 1000 unit increase.
Methods: Give-me-five trial is a prospective phase
II study designed for the treatment of PCa patients with
ultra-hypofractionated radiotherapy scheduled in 5
fractions with 36.25 Gy delivered to the whole prostate
CO090

and a concomitant boost of 37.5 Gy to the dominant INTRODUCING INFORMATION ON SALIVA


intraprostatic lesion (DIL) identified by multiparame- MICROBIOTA INTO TOXICITY MODELING:
tric MRI. T2-weighted (T2W) MRI sequences acquired PRELIMINARY RESULTS FROM A TRIAL
with homogenous characteristics (0.59x0.59x3 mm3 N.A. Iacovelli1, A. Cavallo 2, T. Rancati 3,
voxel size, XX Te, YY Tr) on a 1.5T Magnetom L. De Cecco4, E. Mancinelli 4, M.S. Serafini4,
Avantofit scanner (Siemens) were selected and the pro- A. De Vecchi4, N. Facchinetti1, T. Di Florio3,
state gland contours were analyzed. The extraction of E. Ivaldi1, D.A. Romanello1, S. Alfieri5, L. Licitra6,
radiomic features (shape, first-order statistics and textu- C. Fallai1, R. Valdagni7, E. Orlandi1
ral features) was performed using the IBEX software. 1Fondazione IRCCS Istituto Nazionale dei Tumori,
We tested association of each radiomic features with Radiation Oncology Unit 2, Milan; 2Fondazione IRCCS
Gleason score (GS, 3+3 vs 3+4 vs 4+3), extracapsular Istituto Nazionale dei Tumori, Medical Physics Unit,
extension (ECE, 1/2 vs 2 vs 3) score, Prostate Imaging Milan; 3Fondazione IRCCS Istituto Nazionale dei
– Reporting and Data System (PIRADS, 2/3 vs 4 vs 5) Tumori, Prostate Cancer Program, Milan; 4Fondazione
score and risk class (intermediate vs low), and selected IRCCS Istituto Nazionale dei Tumori, Platform of
the feature with the lowest p-value in each cluster as Integrated Biology- Department of Applied Research
representative. Statistical analysis was performed with and Technology Development, Milan; 5Fondazione
SAS/STAT® software. IRCCS Istituto Nazionale dei Tumori, Head and Neck

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Medical Oncology Department, Milan; 6Fondazione design of possible interventional trials to reduce tox by
IRCCS Istituto Nazionale dei Tumori, Head and Neck modifying saliva MB before RT start.
Medical Oncology Department- University of Milan;
7Fondazione IRCCS Istituto Nazionale dei Tumori,

Radiation Oncology Unit 1- Prostate Cancer Program-


CO091
University of Milan, Italy GLI.F.A. PROJECT: GLIOBLASTOMA MULTIFOME
Aims: A mono-institutional trial was set up to inve- RADIOMICS FEATURES ANALYSIS FOR THE
stigate the role of saliva/gut microbiota (MB) in toxicity
(tox) after RT for head & neck (HNC) and prostate can-
PREDICTION OF PATIENTS OUTCOMES
S. Chiesa1, I. Palumbo2,3, F. Beghella Bartoli1,
cers. We here focus on introducing information on sali- C. Mazzarella1, M. Iacco2, C. Masciocchi1,
va MB into a normal tissue complication probability M. Lupattelli3, A. Rongoni4, R. Russo5, G. Sabatino6,
(NTCP) model for acute oral mucositis (OM) in HNC. P. Floridi4, N. Dinapoli1, S. Longo8, L. Boldrini1,8,
Methods: 130 consecutive HNC patients (pts) recei- R. Tarducci4, M. Balducci1,8, C. Aristei2,3,
ving either postoperative (60-66Gy @2Gy/fr) or radical V. Valentini1,8
IMRT (70Gy @2-2.12Gy/fr) with/o chemotherapy were 1Fondazione Policlinico Universitario A. Gemelli
enrolled. A detailed evaluation was done pre, during IRCCS, UOC di Radioterapia Oncologica,
and at RT end, including saliva MB measurement. Dipartimento Diagnostica per Immagini, Radioterapia
Saliva samples were collected using OMNIgene oral Oncologica ed Ematologia, Roma; 2Sezione di
devices (DNA genotek). DNA extraction was carried Radioterapia Oncologica, Dipartimento di Scienze
out using the QIAamp-DNA-Stool-Mini-Kit (Qiagen). Chirurgiche e Biomediche, Università degli Studi di
The bacterial 16S ribosomal-RNA reads were analyzed Perugia; 3Struttura Complessa di Radioterapia
with the QIIME software and pooled in Operational Oncologica, Azienda Ospedaliera di Perugia;
Taxonomic Units (OTUs) with Uclust software. 4Struttura Complessa di Fisica Sanitaria Azienda
Grade≥3 CTCAE acute OM (OM3) was the primary Ospedaliera di Perugia; 5Fondazione Policlinico
endpoint. Among 24 pts selected for this preliminary Universitario A. Gemelli IRCCS, UOC di Radioterapia
analysis, 13 scored OM3. Unsupervised clustering Oncologica, Dipartimento Diagnostica per Immagini,
(fuzzy c-means) was used to separate pts into 2 MB clu- Radioterapia Oncologica ed Ematologia, Università
sters, based on relative abundance of OTUs at bacterial Cattolica del Sacro Cuore, Istituto di Radiologia, Roma;
class level before RT start. Information on MB cluste- 6Fondazione Policlinico Universitario A. Gemelli
ring was introduced as a dose-modifying factor into a IRCCS, Istituto di Neurochirurgia, Roma; 7Struttura
logistic NTCP model. Dosimetric variables were deri- Complessa di Neuroradiologia, Azienda Ospedaliera di
ved from a previous model for OM3: dose to oral cavity Perugia; 8Università Cattolica del Sacro Cuore, Istituto
(Equivalent Uniform Dose, OCEUD, with n=0.05) and di Radiologia, Roma, Italy
mean dose to parotid glands (PGmD).
Results: Unsupervised clustering identified 12 pts Aims: A comprehensive analysis of Glioblastoma
included in a first (A) and 12 in a second MB cluster (B). multiforme (GBM) heterogeneity could be useful to
4/12 (33.3%) and 9/12 (75%) pts with OM3 were found personalize treatment strategies. Radiomic provides a
in clusters A and B, respectively (p=0.05). MB clustering tool for quantification and visualization of intra-tumor
resulted in AUC=0.71 (95%CI=0.50-0.87) for OM3 heterogeneity and converts images into mineable data.
discrimination. The following bacterial classes presented The multi-centric study, the GLI.F.A. (Glioblastoma:
with significantly different abundances (p<0.01) in MB advanced Imaging Features Analysis) Project, aims to
clusters A and B: Proteobacteria_ Gammaproteobacteria investigate whether radiomic feature-based MRI signa-
and Acidobacteria-6 were more abundant in cluster A, ture allow to predict clinical outcomes in GBM.
while Bacteroidetes_Bacteroidia, Firmicutes_Clostridia Methods: Patients affected by GBM, who were
and Actinobacteria_ Corio-bacteriia were more abundant treated with surgery and standard chemo-radiotherapy,
in cluster B. NTCP model including only dosimetry had were considered. Two radiomic analysis were perfor-
OR=1.19 (for 1 Gy increase) for PGmD and 1.03 for med: one on pre-operative magnetic resonance images
OCEUD (AUC=0.80, 95%CI=0.59-0.94). When MB clu- (MRI) and the other as a delta-radiomic evaluation
stering was introduced resulted in OR=4.1 and AUC=0.85 using MRIs after radiotherapy, during adjuvant che-
(95%CI=0.64-0.96), with 10% decrease of both high and motherapy and follow-up. The Gross Tumor Volume
low residual pts. (GTV) (i.e. the macroscopic lesion at the baseline) and
Conclusions: This preliminary study demonstrates Clinical target Volume (CTV) (i.e. the tumor bed +/-
the possibility of introducing pts-specific MB data into residual mass + 1.5cm of margin) were contoured in the
NTCP model, through use of unsupervised clustering to contrast-enhanced T1 and T2 and T2-FLAIR weighted
exploit the whole MB information (292 classes) without images as region of interest (ROI). The MODDICOM
dramatically increasing the number of features to be software was used for the extraction of MRI features.
included in the model. Results in a small sample of The Mann Whitney or t-test were used to assess the dif-
HNC pts seem promising, indicating that pts with/o ference in radiomic features between different respon-
acute OM3 have different constitutional saliva MB pro- ses and the Log-rank test for Kaplan-Meier curves was
files. If confirmed in the whole population, this could used to evaluate the significance of the features, using
represent an important finding for tox prediction and their median value to categorize the continue variables.

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The overall survival (OS), the progression fee survival


(PFS) and the response to radio-chemotherapy (RTCT)
CO093

were considered.
Results: Forthy-three patients, treated from 2014,
RADIOMIC ANALYSIS IN LOCALLY ADVANCED

with a median age of 63 years (range 45-80) were enrol-


PANCREATIC CANCER TREATED WITH STEREO-

led. The first analysis on pre-operative MRI extracted


TACTIC BODY RADIATION THERAPY
F. Gregucci1, R. Mazzola2, I. Bonaparte1, A. Surgo1,
92 features from each ROI. The textural features corre- A. Fiorentino1, F. Alongi2,3
lated with PFS, LC and response to RTCT on T1 images 1Radiation Oncology Department, General Regional
and one features, describing the homogeneity, impacted
on all three clinical outcomes (Table1). For delta-radio- Hospital F. Miulli, Acquaviva delle Fonti-Bari;
2Radiation Oncology Departement, IRCCS Sacro Cuore
mic analysis, the pre-RTCT MRI and the MRI after the
6th cycle of chemotherapy resulted useful for signifi- Don Calabria Hospital, Negrar-Verona; 3Radiation
cant features: the textural features for both MRI, the Oncology Department, University of Brescia, Brescia,
first order and morphological features for pre-RTCT Italy
MRI (Table 2). Aim: Aim of this study was to evaluate the relation-
Conclusions: This radiomic analysis suggests that is ship between radiomic analysis based on contrast-
possible to stratify patients according MR based quan- enhanced computed tomography (CT) images and the
titative imaging. A prospective enrollment is ongoing in local control (LC) to treatment and progression free-
order to confirm the role of imaging features in iden- survival (PFS) in a retrospective cohort of 37 patients
tifying, according to other known prognostic factors, affected by locally advanced pancreatic cancer (LAPC)
high risk patients that could benefit of dose-dense stra- treated with stereotactic body radiation therapy
tegies. (SBRT).
Methods: Gross tumor volume of the primary disea-
se (GTVp) for each patient was contoured by two
expert Radiation Oncologists. A total of 30 features
were derived and selected from the CT images and
Tables 1 and 2.

grouped by intensity, shape and second or higher order


features, according to significant results by literature.
Radiomic analysis were performed using an imaging
biomarker explorer software that runs in MatLab
platform. Based on median value of each variables, the
continuous quantitative variables were converted to
dichotomous variables. The univariate and multivariate
logistic regression was performed to investigate the pre-
dictive value of each radiomic features relatively to LC.
The prognostic value of radiomic analysis relative to
PFS was evaluated with univariate Cox regression. The
statistical analysis was carried out in R platform.
Results: The main clinical and treatment characteri-
stics of the study cohort were reported in a previous
published paper [https://doi.org/10.1007/s00066-018-
1306-2]. The 30 radiomic features were divided in 12
intensity (IntensityHistogram) features, 6 shape (S) fea-
tures and 12 second or higher order
(GrayLevelCooccurence Matrix25-GLCM25/ Neigh
borIntensityDifference25 -NID25) features. The main
summary indicators of the radiomic variables were
reported in Table 1. From the analysis of textural data,
4 predictors resulted significant at univariate test for
LC: IH_Energy(p=0.05), S_Compactness(p=0.05),
S_Mass(p=0.05) and GLCM25_Correlation(p=0.05).
The multivariate analysis showed statistical significan-
CO092

ce for 2 variables: IH_Energy(p=0.05) and


ABSTRACT WITHDRAWN GLCM25_Correlation(p=0.05). The Area Under the
Curve for the multivariate logistic regressive model was
0.783 (95% CI 0.571-0.905). Between all radiomic fea-
tures, only the GLCM25_Correlation was significantly
correlated with PFS (hazard ratio 2.5;95%CI 1-
6.3,p=0.04).
Conclusion: Radiomic analysis based on contrast-
enhanced CT images in LAPC treated with SBRT iden-

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tifies predictive and prognostic imaging biomarkers for and with a Pearson correlation coefficient less than 30%
LC and PFS, respectively, representing a promising were selected. The model performance was then asses-
field of research. sed on the testing data.
Results: From the initial database of 217 LARC pts,
4 pts were discarded for missing data regarding the end-
point. 2606 features were extracted and tested from the
Table 1. Main summary indicators of the radiomic variables with symmetric (A) and

pre- and post- nCRT GTV. Four features were identified


asymmetric (B) distribution.

after the selection process: i) medianFD30,60.delta (the


variation between pre- and post- MRI median fractal
dimension); ii) F_szm.lzlge1.1.delta (the variation
between pre- and post- MRI of the value of a radiomic
feature using Laplacian of Gaussian (LoG) filter;
F_morph.pca.flatness.pre (the ratio between the minor
axis and the major axis of the ellipsoid calculated on the
volume of the GTV of the pre-MRI) and iv)
F_cm.clust.prom0.6.pre (a radiomic feature extracted
from the co-occurrence matrix of the pre-MRI using
(LoG) filter). A logistic regression based model was
provided with a testing set balance accuracy of 79%, a
sensitivity of 0.71% and a specificity of 0.86%.
Conclusions: In this single center study, Delta
Radiomics appears to have a predictive role in charac-
terizing tumor behavior in rectal cancer after nCRT. The
early prediction of biological aggressiveness could help
in treatment personalization and follow-up intensifica-
tion in high risk pts. Further studies are needed to con-
CO094 firm these results on an independent validation dataset.
DELTA RADIOMICS TO ASSESS RECTAL CANCER
Table 1. Patient characteristics.
BEHAVIOR AND PREDICT DISTANT METASTASIS
C. Casà1, G. Chiloiro1,2, J. Lenkowicz1, P. Rodriguez- Age: Median (range), years 64 (26-83)
Carnero3, L. Boldrini1,2, B. Barbaro1,2,
D. Cusumano1,2, P. De Franco1, N. Dinapoli1,2, Sex Female 79 (36.4%)
C. Masciocchi1, E. Meldolesi2, A. Damiani1, Male 138 (63.6%)
M.A. Gambacorta1,2, R. Manfredi1,2, V. Valentini1,2
1Università Cattolica del Sacro Cuore, Roma, Italy; Stage (cT) cT2 15 (6.9%)
2Fondazione Policlinico Universitario A. Gemelli
cT3 134 (61.8%)
IRCCS, Roma, Italy; 3Radiology Department, La cT4 68 (31.3%)
Princesa University Hospital, Madrid, Spain
Aims: To assess the role of the variation of radio- Stage (cN) cN0 13 (6.0%)
mics parameters between staging and post- neoadjuvant cN1 71 (32.7%)
chemoradiation (nCRT) re-staging Magnetic cN2 133 (61.3%)
Resonance Imaging (MRI) for the prediction of 2 years
Distant Metastasis rate (2yDM) in a single institution TRG (according to Mandard) TRG 1: 55 (25.4%)
cohort of patients (pts) affected by locally advanced TRG 2: 44 (20.3%)
rectal cancer (LARC). TRG 3: 89 (41.0%)
Methods: Data regarding 217 LARC pts treated TRG 4: 17 (7.8%)
with nCRT in a single institution from November 2007 n.a.: 12 (5.5%)
to January 2016 were retrospectively collected. Only
pts with available pre- and post-nCRT diagnostic MRI Distant Metastasis at 2 years No: 177 (81.6%)
and with at least 3 years of follow-up were selected. A Yes: 36 (16.6%)
radiation oncologist (RO) and a radiologist defined the n.a.: 4 (1.8%)
Gross Tumour Volume (GTV), with the validation of
another RO. Pts were randomly assigned to a training
group (90% of the dataset) and a testing group (10%),
the same outcome proportion was maintained between
the two groups. The features selection process was
performed on the training set with a 5-fold cross-valida-
tion and only features significative (p<0.05 at Wilcoxon
Mann-Withney test) for at least 3 times after 5 iterations

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

curve of the associated Logistic Regression model


(AUC = 0.847).
CO095

Conclusions: These results suggest that radiomic


can help in detecting, under specific circumstances (e.g.
LOCAL RESPONSE BASED ON RADIOMIC ANALY-

Skewness greater or equal than 0.5), local recurrence at


SIS IN EARLY-STAGE NON-SMALL CELL LUNG

12 months after SABR and that this decision support


CANCER TREATED WITH STEREOTACTIC

system could potentially allow a personalized treatment


ABLATIVE RADIATION THERAPY
S. Chiesa1, R. Gatta1, A. Martino1, A. Piras2,
D. Cusumano3, L. Boldrini1,2, C. Masciocchi1, strategy for early salvage therapy.
M. Massaccesi1, N. Dinapoli1, F. Cellini1,2,
G.C. Mattiucci1,2, G. Mantini1,2, M. Balducci1,2,
V. Valentini1,2
1Fondazione Policlinico Universitario A. Gemelli

IRCCS, UOC di Radioterapia Oncologica,


Dipartimento Diagnostica per Immagini, Radioterapia
Oncologica ed Ematologia, Roma; 2Università
Cattolica del Sacro Cuore, Istituto di Radiologia, Roma;
3Fondazione Policlinico Universitario A. Gemelli

IRCCS, UOC di Fisica Sanitaria, Dipartimento


Figure 1.

Diagnostica per Immagini, Radioterapia Oncologica ed


Ematologia, Roma, Italy
Purpose: Stereotactic ablative radiation therapy
CO096
(SABR) is a treatment option for early-stage non-small
cell lung cancer (NSCLC). This study investigates the
RADIATION-INDUCED GENE EXPRESSION

performance of radiomic features for disease recurrence


PROFILING OF DIFFERENT BREAST CANCER

after stereotactic ablative radiation therapy (SABR).


SUBTYPES
V. Bravatà1, L. Minafra1, FP. Cammarata1, R. Musso1,
Methods and Materials: Patients with early stage G. Pucci1, M. Calvaruso1, G. Savoca1, M. Spada2,
NSCLC, treated with SABR were considered. The lung I. Fazio3, G. Russo1, G.I. Forte1
lesions received a total dose of 42 Gy in 3 or 50 Gy in 1Istituto di Bioimmagini e Fisiologia Molecolare-
5 fractions according to the site. A 4D-CT were perfor-
Consiglio Nazionale delle Ricerche (IBFM-CNR),
med to delineated the internal target volume (ITV) and
Cefalù (PA); 2Fondazione Istituto G. Giglio, Cefalù
the radiomic features were extracted from the ITV
(PA); 3Casa di Cura Macchiarella, Palermo, Italy
reported on average intensity projection (AIP), through
the use of MODDICOM software. The Wilcoxon Mann Aims: The aim of this study was to assess the gene
Whitney test was applied to evaluate the significance of expression changes induced by high doses of ionizing
the features; afterwards a Logistic Regression model radiation (IR) on immortalized and primary BC cell
was built for each significant feature. The response to lines grouped according to human epidermal growth
SABR according to RECIST Criteria was considered. factor receptor (HER2), estrogen and progesterone
Results: Overall 42 early stage NSCLC patients receptors status (ER, PR), in order to study how HR sta-
and 47 lesions, receiving SABR, were considered for tus influences the radiation response, affecting clinical
this analysis. Thirteen lesions presented a local recur- outcomes. Radiation therapy (RT) is a crucial treatment
rence. Ninety-four features were extracted using MOD- for BC, either alone or in combination with other treat-
DICOM software and the correlation between the radio- ment modalities, however, RT treatment planning take
mic features and the local recurrence at 12-24 and 36 in account physic metrics, nonetheless it emerges the
months was investigated. Seventeen features showed a necessity to include biological biomarkers of tumor
significant correlation (p<0.01) with local recurrence at radiosensitivity, to optimize therapeutic efficacy.
12 and 24 months at Wilcoxon Mann Whitney test: 3 Methods: A genomic approach using cDNA
intensity based statistical features; 2 Grey level co- microarray was utilized to analyze gene expression pro-
occurrence based features-Texture features (GLCM); 6 files induced by two doses (9 and 23 Gy) of IR, 24 h
Grey level run length based features-Texture features post-treatment, on in vitro and ex-vivo models (e.g.,
(GLRLM); 6 Grey level size zone based features- primary cells). For this purpose, three human immorta-
Texture features (GLDZM), according to Image bio- lized cell lines (MCF10A, MCF7, and MDA-MB-231)
marker standardization initiative v.7 (https://arxiv.org/ and three primary cell cultures (HMEC, BCpc7, and
abs/1612.07003). No correlation was found between BCpcEMT), obtained from both tumor and healthy spe-
radiomic features and local recurrence at 36 months. At cimens, were classified into three BC groups: 1) the tri-
the kernel density estimation of Skewness (p<0.01 at ple negative group (ER−/PR−/HER2−), including
the Mann Whitney test) is shown on the picture on the MDA-MB-231 and BCpcEMT cells; 2) the HR positive
left for both, the positive (blue) and negative (red) group (ER+/PR+/HER2−), including MCF7 and BCpc7
lesions, on Figure 1. In the middle the distribution of cells; 3) a group originating from healthy tissue, inclu-
positive and negative outcomes (same colors) depen- ding MCF10A and HMEC cells.
ding on the value of Skewness and on the right the ROC Results: Overall, the IR-induced gene expression

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Oral Communications

profiles and pathways appear to be cell-line dependent lation, nucleosomes, chromosome, and telomere main-
and linked to HR status. Precisely, few genes (11) and tenance.
one pathway were commonly deregulated in the healthy Conclusions: Genomic biomarkers and gene-signa-
samples. Instead, BC cells shared well defined respon- tures of specific tumor subtypes, selected according to
ses to RT according the HR status. Indeed, while the HR their HR status and molecular features, could be used to
positive cells activate cellular process involved in cell achieve personalized biological-driven RT treatments
cycle regulation, repairing DNA strand breaks, and cell planning alone or in combination with targeted thera-
survival/death balance through the activation of apopto- pies.
sis signaling, particularly driven by the activation of *This study was supported by GeSeTON project
p53 signaling pathway, the triple negative cells respon- (funded by Italian MISE grant n. 489 of 21/02/2018).
se in strongly characterized by chromatin remodeling
mechanisms, through the activation of cell cycle regu-

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Discussed Poster

advanced gastroesophageal junction tumor could be


evaluated by GI AIRO board for a future investigation.
DP01

Methods: PRIDE (2) is a multicenter observational


trial with the aim to obtain a prediction model of a
MULTIMODAL APPROACH WITH 18-F-FDG PET-CT

pathologic complete response(pCR) after nCRT delive-


AND MPMRI AS PREDICTOR FOR PCR IN LOCAL

red according to CROSS in potentially resectable,


ADVANCED ESOPHAGEAL CANCER TREATED

locally advanced (cT1b-4aN0-3 M0) esophageal or


WITH CROSS REGIMEN. IS ORGAN-SPARING

gastroesophageal junction tumor, squamous cell carci-


POSSIBLE?
F. De Renzi1, S. Bissoli2, P. Bullian3, C. Furlan1,
R. Malaguti1, C. De Toffol4, F. Martinelli2, T. Iannone1 noma or adenocarcinoma. 200 patients should be inclu-
1Radioterapia, Ospedale San Martino di Belluno;
ded. Diagnostic work-up and staging for esophageal
2Medicina Nucleare, Ospedale San Martino di Belluno;
cancer includes DW MRI, DCE MRI and 18-F-FDG
3Oncologia Medica, Ospedale Santa Maria del Prato di
PET-CT prior to, during (after 10-15 fractions of
radiotherapy) and after nCRT with an optional endosco-
Feltre; 4Fisica Sanitaria, Ospedale San Martino di pic assessment. MRI post performed 6–8 weeks after
Belluno, Italy the completion of nCRT, and no sooner than 2 weeks
Purpose: In locally advanced esophageal cancer, before surgery. Blood samples at 3 time points and 1
neoadjuvant chemoradiotherapy (nCRT) followed by postchemoradiation endoscopic and endosonographic
surgery improved survival over surgery alone. nCRT assessment. Primary endpoint: pCR prediction.
according to the CROSS1 regimen followed by surgery Secondary: PFS e OS.
may be considered as standard of care. In our Center, Results and Conclusions: PRIDE is a clinical onco-
from 2010 to date, 75 patients with a diagnosis of car- logic ongoing trial, based on an interesting protocol.
cinoma of thoracic tract or lower third of esophagus Endoscopic biopsy after chemoradiotherapy for
were evaluated for a radiation treatment. In 2019 we esophageal cancer is a very specific but not a sensitive
have treated locally advanced gastroesophageal junc- method.3 A model based on mpMRI, FDG PET-CT and
tion carcinoma according CROSS for a preoperative circulating tumor DNA biomarkers could lead to an
approach: carboplatin/paclitaxel-based chemoradiothe- active surveillance after nCRT in patients with a clinical
rapy with radiation doses of 41.4 Gy (1.8 Gy/fr).18-F- complete response, obtaining a prediction of pCR
FDG PET-CT prior to nCRT was always requested and without surgical resection, improving quality of life and
used to identify GTV and Nodal Volume during contou- reducing costs.
ring.In GI multidisciplinary group, we have discussed
about PRIDE trial.2 Here we describe that protocol of References
study, because an organ-sparing approach in local 1. van Hagen P et al. N Engl J Med 2012;366:2074-84.

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Discussed Poster

2. Borggreve AS et al. BMC Cancer 2018; 18:1006


3. van Rossum PSN et al.Gastrointest Endosc. 2016;83(5):866
DP03
STRAIT-LUC TRIAL: STEREOTACTIC
DP02 RADIOTHERAPY AND IMMUNOTHERAPY FOR
BRAIN METASTASES FROM NON SMALL CELL
PHASE II STUDY OF FOLFIRINOX-BASED INDUC- LUNG CANCER (NSCLC): A PROSPECTIVE
TION CHEMOTHERAPY FOLLOWED BY RADIO- OBSERVATIONAL MULTICENTER TRIAL ON
CHEMOTHERAPY IN LOCALLY ADVANCED PAN- BEHALF OF BRAIN AND THORACIC ONCOLOGY
CREATIC CANCER: PRELIMINARY RESULTS
P. Trecca, M. Fiore, R. Coppola, M. Miele,
NATIONAL GROUP OF AIRO
E. Olmetto1, S. Scoccianti1, R. Di Franco2,
G.M. Petrianni, L.E. Trodella, R.M. D’Angelillo, E. Maranzano3, G. Beltramo4, U. Ricardi5, M.F. Osti6,
L. Trodella, S. Ramella L. Fariselli7, N. Giaj-Levra8, A. Bruni9, P. Matteucci10,
Università Campus Bio-Medico Roma, Italy S. Pedretti11, M. Krengli12, P. Ciammella13,
F. Pascqualetti14, M. Taraborrelli15, A. Merlotti16,
Purpose: To evaluate the safety and efficacy of D. Greto1, G. Piperno17, M. Trovò18, A. Tagliagambe19,
FOLFIRINOX-based induction chemotherapy followed L. Paoletti20, A. Fozza21, M. Sepulcri22, V. Nardone23,
by a high weekly dose of gemcitabine-based radioche- A.R. Filippi24, P. Navarria25, V. Scotti1
motherapy in patients with borderline resectable or 1Radiation Oncology Unit, Department of Experimental
unresectable locally advanced pancreatic cancer. and Clinical Biomedical Sciences Mario Serio, AOU
Materials and Methods: From October 2015 Careggi, University of Florence; 2Istituto Nazionale
twenty-six patients with pancreatic cancer have been TUMORI-IRCCS--Fondazione G. Pascale- Napoli;
included in the study. In all cases an accurate pre-treat- 3Radiotherapy Oncology Centre S. Maria Hospital,
ment staging including laparoscopy and 18F-FDG Terni; 4Cyberknife Centro Diagnostico Italiano Milano;
PET/CT has been performed. Patients received che- 5Department of oncology, Radiotherapy unit, University
motherapy with FOLFIRINOX regimen for four doses. of Turin; 6Uoc radioterapia Aou sant’Andrea facoltà
Patients without disease progression after restaging medicina e psicologia Universita Sapienza, Roma; 7Uo
received conformal radiation therapy and concurrent radioterapia Fondazione IRCCS istituto neurologico
gemcitabine at the dose of 600 mg/mq weekly. Carlo Besta, Milano; 8Dipartimento di radioterapia
Results: Further to the results of the pre-treatment oncologica avanzata, IRCCS Ospedale Sacro Cuore
workup, twelve patients (46%) were excluded from the Don Calabria, Negrar, Verona; 9Radiotherapy Unit,
protocol because of the evidence of metastatic disease, Department of Oncology and Hematology, University
and thus a total of 14 patients were consequently enrol- Hospital of Modena; 10Radioterapia Oncologica
led. Grade 3-4 toxicity was observed in two patients Campus Biomedico, Roma; 11ASST Spedali Civili di
(grade 3 elevated levels of alkaline phosphatase in one Brescia e Università degli studi di Brescia, U.O.
case; grade 4 febrile neutropenia in another one). Three Radioterapia oncologica, Brescia; 12Radiation
patients (21.4%) experienced disease progression after Oncology, University Hospital Maggiore della Carità,
induction chemotherapy. One patient has not yet com- Novara; 13Radioterapia Oncologica, AUSL-IRCCS
pleted the induction phase at the time of evaluation. Ten Reggio Emilia; 14Radiation Oncology, Azienda
patients completed the radiochemotherapy protocol. Ospedaliero Universitaria Pisana, Pisa; 15U.O.C.
Only haematological grade 3-4 toxicities were obser- Radioterapia Oncologica, Ospedale Clinicizzato SS
ved. Seven patients were evaluated through surgical Annunziata, Università G.D'Annunzio, Chieti;
16Radiation Oncology A.S.O. S.Croce e Carle, Cuneo;
exploration and six patients underwent surgical radical
17Division of Radiation Oncology , European Institute of
resection. With a median follow-up of 13 months, the
median PFS was 14.2 months. One-year PFS was Oncology, Milan; 18Department of Medical Area,
62.3%. One-year and two-year LC were 92% and 61%, University of Udine, ASUIUD, Udine; 19U.O.C.
respectively. One-year MFS was 72% (median, 14.2 Radioterapia Carrara (MS); 20Sc Radioterapia
months). Median OS was 12.8 months. One-year OS, Ospedale Santa Maria Annunziata, Bagno a Ripoli (FI);
21Radioterapia Oncologica A.S.O. SS Antonio Biagio e
two-year OS were 66% and 35%, respectively.
Conclusions: Our preliminary results suggest that Cesare Arrigo, Alessandria; 22U.O.C. Radioterapia
this protocol treatment is feasible with an acceptable IOV-IRCCS Padova; 23UOC Radioterapia, Ospedale
toxicity profile for patients with borderline resectable del Mare, Napoli; 24Radiation Oncology Unit,
and unresectable pancreatic cancer. An accurate staging Fondazione IRCCS Policlinico San Matteo, Pavia;
25Radiotherapy and Radiosurgery Department
is crucial for the appropriate treatment of patients.
Humanitas Research Hospital, Rozzano (MI), Italy
Aims: The STRAIT- LUC trial is the result of the
collaboration between AIRO Brain group and AIRO
Thoracic Oncology group to investigate the association
between Stereotactic Radiotherapy (SRT) and
Immunotherapy (IT) for the treatment of brain metasta-
ses (BM) from NSCLC. Many retrospective trials, with

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a small number of patients and with several bias, sugge- Homogeneity Index (HI).
st that concomitant treatment may improve the outco- Methods: Image data of 4 patients with histological-
mes of these patients. Primary endpoints of the study ly diagnosed medulloblastoma who underwent CSI
are safety, feasibility and intracranial control asses- were used. The prescription dose was 25.5 Gy in 15 fx
sment; secondary endpoint is the evaluation of Quality for whole brain and spinal cord, with a sequential boost
of Life (QoL). of 10.8 Gy in 6 fx on the whole brain and 20Gy in 10 fx
Methods: Data about patients with brain metastases on the posterior cranial fossa. The TIJJ IMRT technique
from NSCLC treated with concomitant IT and SRT will was used to create the delivered plan. The Oncentra
be prospectively collected in different Italian MasterPlan treatment planning system was employed to
Radiotherapy Centers. Eligibility criteria are: patients delineate the planning target volume (PTV) and organs
with a maximum of 10 brain lesions to be treated with at risk (OARs) on CT images with the patients in prone
single fraction SRT or hypo-fractionated SRT (3-5 frac- position using a personalized immobilization device.
tions); concurrent SRT and IT, defined as IT and SRS The PTVcns included the PTVbrain and the
being administered within one month of one another; PTVspinal1/2. The PTVbrain included the whole brain
SRT performed during a first line, a second line or a with a 3 mm isotropic expansion. The PTVspinal1/2
further line of IT with or without the association of che- included C1 through S3 with a 5 mm isotropic expan-
motherapy. Toxicity such as the development of brain sion. The PTVbrain and PTVspinal1/2 have been used
radionecrosis will be evaluated according to the to create three different IMRT plans, each with a proper
CTCAE v.4.1. MRI scanning will be performed every 3 isocenter. The three isocenters were collinear and pla-
months during follow-up and radiological response will ced near the patient’s midline. The PTVbrain and
be evaluated according to the i-RANO criteria. Local- PTVspinal1/2 were modified every 5 fx in order to stag-
PFS and Distant-PFS, defined as the time from SRT to ger the field edges, keeping the three isocenters fixed,
local progression of the treated lesions and to the appea- thus shifting the junctions (PTVbrain-PTVspinal1 and
rance of new BM, respectively, will be analyzed. PTVspinal1-PTVspinal2). The field set of IMRTbrain
EORTC QL 30 BN module will be used to assess contained seven fields with gantry angles of 0°, 50°,
patients QoL. Survival analysis will be performed using 75°, 110°, 245°, 280° and 315°, respectively. The field
Kaplan-Meyer survival curves and log-Rank test. sets of IMRTspinal1/2 had five radiation fields with
Results: Fifty patients are expected to be enrolled gantry angles of 295°, 325°, 0°, 35° and 65° respecti-
during a period of two years. An interim analysis will be vely.
performed after the enrollment of the first 30 patients. A Results: The modified TIJJ IMRT technique rea-
pre-planned subgroup analysis will be performed accor- ched the goal of the 95% isodose curve covering at least
ding to the number of BM (1 vs 2-4 vs 5-10), the num- 99% of the PTV and respected all OARs constraints.
ber of SRT fractions (1 vs 3 vs 5), PDL-1 level. Use of The CI and HI were 0.79+-0.04 and 0.18+-0.04 respec-
corticosteroids (dose and duration) will be registered. tively (mean+-sd). In addition, neither cold nor hot
Conclusions: To our knowledge this is the first mul- dosing spots were found in the radiation beams overlap-
ticenter prospective trial evaluating the association of ping regions between the PTVs.
IT and SRT for BM from NSCLC. This trial will contri- Conclusions: Modifying the extension of the PTV
bute to provide evidence to confirm the encouraging every 5 fx in order to change the topography of the
results that were reported by retrospective studies. junctions overcomes problems associated with field
junctions and beam edge matching and improves plan-
ning and treatment setup efficiencies with homogenous
target dose distribution. This technique is a valid option
DP04

for the treatment of medulloblastoma as it is compara-


ble to the helical tomotherapy in terms of CI and HI.
A MODIFIED THREE-ISOCENTER JAGGED-JUNC-
TION (TIJJ) INTENSITY-MODULATED RADIATION
THERAPY (IMRT) APPROACH FOR THE TREAT-
MENT OF MEDULLOBLASTOMA
S. Lillo1, A. Cacciola1, F. Arena1, D. Cambareri1,
L. Campanelli1, G.R. Chisari1, V. Davì1, L. Molino1,
I. Napoli1, S. Parisi1, C. Severo1, C. Tamburella1,
C. Vadalà1, R.E. Vadalà1, A. Pontoriero1, G. Iatì1,
P. Delia1, A. Santacaterina2, S. Pergolizzi1
1Radiation Oncology Unit - Department of Biomedical,

Dental sciences and Morphological and Functional


Images, University of Messina; 2Azienda Ospedaliera
Papardo, Messina, Italy
Aims: Craniospinal irradiation (CSI) is one of the
most difficult treatments. The aim of this study was to
Figure 1.

show the efficiency of a modified three-isocenter jag-


ged-junction (TIJJ) Intensity-Modulated Radiation
Therapy (IMRT) in terms of Conformity Index (CI) and

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Discussed Poster

of the adaptive workflow resulted to be advantageous in


all the patients: mean PTV V95% increased by 10.8%
DP05

(5.7-20.8) while mean GTV V98% of 12.6% (7.3-17.7).


Also OARs V33 and V25 showed a positive trend in
ONLINE ADAPTIVE MRI GUIDED RADIOTHERAPY

avoiding unnecessary irradiation. Dosimetric results are


IN LOCALLY ADVANCED PANCREATIC CANCER:

summarized in Table 1. Acute G1 diarrhea was obser-


FIRST APPLICATION IN ITALY
L. Boldrini1, A. Romano2, L. Placidi1, G. Chiloiro1,
D. Cusumano1, M.V. Antonelli1, C. Votta1, F. Cellini1, ved in one patient (CTCAE v.4). At median follow-up
G.C. Mattiucci1, M.A. Gambacorta1, V. Valentini1 of 14 months all patients were alive with 75% local
1UOC control rate.
Radioterapia Oncologica, Fondazione
Conclusion: Online adaptive MRgRT is associated
Policlinico Universitario A. Gemelli IRCCS, Roma;
2Dipartimento di Scienze Biomediche Avanzate, with acceptable toxicity and promising local control
rates in LAPC. Daily re-optimization prevents the
Università Federico II, Napoli, Italy
occurrence of high-doses to OARs, increasing the
Aims: Magnetic Resonance-guided Radiation safety of stereotactic treatment for LAPC.
Therapy (MRgRT) allows more precise identification of
therapy volumes and reliable online monitoring of treat-
ment delivery, using high-temporal resolution MR cine
DP06
imaging. MRgRT allows to online adapt the treatment
plan (i.e. Online Adaptive RT) optimizing the dose
RADIOMICS ANALYSIS OF MRI IN PATIENTS

distribution on patient’s anatomy of the day, just before


WITH LOCALLY ADVANCED RECTAL CANCER,

fraction delivery. Aim of this study is to evaluate the


CORRELATION WITH TRG (TUMOR REGRESSION

OA workflow implemented in our institution for locally


GRADE)
P. Cocuzza1, S. Montrone1, N. Giannini1,
advanced pancreatic cancer (LAPC) patients in terms of G. Gadducci1, E. Calistri1, C. Arena2, M. Gabelloni2,
target coverage and organs at risk (OARs) sparing, L. Del Secco2, E. Neri2, F. Paiar1
comparing the adapted treatment plan with both the 1Azienda Ospedaliero Universitaria Pisana – U.O.
baseline plan and the “predicted” one, that is the base-
line plan evaluated on the patient's daily anatomy. Radioterapia; 2Azienda Ospedaliero Universitaria
Methods: We retrospectively analyzed LAPC Pisana – U.O. Radiologia 3, Pisa, Italy
patients treated with MRgRT using the OA workflow Aims: To evaluate the correlation between MRI tex-
from January to August 2018. MRgRT was delivered ture analysis before and after preoperative radioche-
using video-assisted inspiratory breath-hold for a total motherapy (RCT) and Tumour Regression Grade
of 38 fractions with a dose ranging from 30 Gy to 40 Gy (TRG) in locally advanced rectal cancer.
in 5 fractions. Plan quality was assessed using institu- Methods: This is a retrospective study with 53
tional OARs constraints and PTV coverage (V95%), patients, median age of 65 years, diagnosis of locally
GTV (V98%) coverage as secondary quality index. advanced rectal cancer hystologically confirmed. All
Prior to each fraction, alignment daily volumetric MR- patients were treated with neoadjuvant radiochemothe-
imaging was performed. The dose distribution of the rapy followed by Total Mesorectal Excission surgery.
baseline plan was firstly calculated on the anatomy of For the RT were planned 50.4 Gy in 28 fractions; con-
the day, obtaining the “predicted” plan and, if the dose comitant chemotherapy consisted in continuos interve-
distribution did not meet the constraints set in the plan- nous infusion of 5-Fluorouracil (225 mg/m2/die) for 11
ning phase, PTV and OARs were re-contoured within a patients or capecitabine (825 mg/m2/BID) for the
distance of 3 cm from the PTV external edge and a new others; all patients completed the planned treatment and
online “adaptive” plan was generated. underwent surgery 6 - 8 weeks after. All the patients
were studied with a MRI before and after RCT. On the
MRIs the tumour was identified as Region of Interest
(ROI) in the T2-weighted images, contouring was
Table 1. Targets and OARs metrics in terms of mean values before and after the onli-

performed by two radiation oncologist with the supervi-


ne adaptation of the plan.

sion of a dedicated radiologist. On the MRI were analy-


zed 27 radiomics features.
Results: 73% of the study population had a down-
staging after RCT. In particular 11% had TRG1, 45%
had TRG2, 26% had TRG3 and 17% had complete ana-
tomopathological tumor regression (TRG 4). As
showed in table 1, before RCT all 27 radiomics features
analyzed don’t show a significant relationship with
TRG. After RCT, the Cluster Prominence Value resul-
ted the best variable to predict TRG. The post-CRT
Results: Eight patients affected by LAPC were tumor volume is also related to TRG. Cluster
enrolled in this study. Median age was 64 years. Out of Prominence is a measure of the skewness and asymme-
38 total fractions, 26 (68.4%) were adapted and 12 try of the Gray Level Co-occurrence Matrix, a low clu-
(31.6%) were delivered using the baseline plan. The use ster prominence (and cluster shade) value describe

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

many patterns of narrowly represented gray-scale


levels. Post-RCT Cluster Prominence Values, divided
DP07

into the 4 classes of TRG, showed that the values are


higher in patients who have better response to preope-
OPEN SOURCE PLATFORM FOR SEGMENTATION,

rative RCT.
DEFORMABLE IMAGE REGISTRATION, AND FEA-

Conclusion: Our results indicate post-CRT Cluster


TURES EXTRACTION OF LUNG CANCER LESIONS
F. Sanna1, P. Crivelli1, A. Poggiu2, E. Sanna1,
Prominence as the most significative texture analysis R. Montella1, D. Gabriele1, M. Tamponi2, P. Marini2,
features for the correlation with response to treatment : N. Sverzellati3, G.B. Meloni1, M. Conti1
a lower value is correlated with poor tumour regression 1Institute of Radiological Sciences, University of
(TRG 1-2), a higher Cluster Prominence is significantly Sassari; 2ATS, Sardinia Regional Health Service,
correlated to pathological complete response (TRG 4). Medical Physics, Sassari; 3Division of Radiology,
Imaging biomarkers might early identify patients who Department of Medicine and Surgery, University of
will have a complete or non-complete tumor response Parma, Italy
to treatment, allowing individualization of medical and
surgery therapy. Further studies are desirable in order to Aims: to show an effective, reliable and free-of-
identify these biomarkers. charge method that allow any institution to conduct
radiomics studies applied to lung cancer.
Methods: The process has been tested on 21
NSCLC (Non Small Cell Lung Cancer): lung lesions
Table 1.

(GTVs) have been identified and segmented with the


Fast GrowCut tool, allowing an advanced semi-automa-
Explanatory variable before RCT p-value Explanatory variable after RCT p-value

Autocorrelation >0.05 Autocorrelation >0.05


tic segmentation that significantly reduced the inter-
Cluster Prominence >0.05 Cluster Prominence 0.037*
operator variability. Only non-contrast enhanced CT
images were used for features extraction, the correspon-
Cluster Shade >0.05 Cluster Shade >0.05
ding enhanced studies were used for a better definition
Contrast >0.05 Contrast >0.05
of GTVs in all doubtful cases.The deformable 3D-
Correlation >0.05 Correlation >0.05
Slicer registration tool, Plastimatch, allowed to distin-
Difference Entropy >0.05 Difference Entropy >0.05
guish GTV from atelectasis or mediastinic borders on
Difference Variance >0.05 Difference Variance >0.05
the contrast-enhanced study. The 3D Slicer Radiomics
Dissimilarity >0.05 Dissimilarity >0.05
tool extracts radiomic features from the non-processed
Energy >0.05 Energy >0.05
raw images. Using Radiomics, 94 features were deter-
Entropy >0.05 Entropy >0.05
mined for each volume: 19 first order, 16 shape, 27
Homogeneity >0.05 Homogeneity >0.05
Gray Level Co-occurrence Matrix (GLCM), 16 Gray
Information Measure of Correlation 1 >0.05 Information Measure of Correlation 1 >0.05
Level Run Length Matrix (GLRLM) and 16 Gray Level
Information Measure of Correlation 2 >0.05 Information Measure of Correlation 2 >0.05 Size Zone Matrix (GLSZM). The free software R has
Inverse Difference >0.05 Inverse Difference >0.05 been used for statistical analysis and graphical results.
Maximum Probability >0.05 Maximum Probability >0.05
Sum Average >0.05 Sum Average >0.05
Sum Entropy >0.05 Sum Entropy >0.05
Sum of Square Variance >0.05 Sum of Square Variance >0.05
Sum Variance >0.05 Sum Variance >0.05
kurtosis >0.05 kurtosis >0.05
Skewness >0.05 Skewness >0.05
Pixel Intensity Mean >0.05 Pixel Intensity Mean >0.05
Pixel Intensity Standard Deviation >0.05 Pixel Intensity Standard Deviation >0.05
Pixel Intensity Median >0.05 Pixel Intensity Median >0.05
Pixel Intensity P25 >0.05 Pixel Intensity P25 >0.05
Pixel Intensity P75 >0.05 Pixel Intensity P75 >0.05
D2D >0.05 D2D >0.05
Volume >0.05 Volume 0.047**

Notes: * r = 0.291; ** r = -0.277

Figure 1.

| 111 |
Discussed Poster

Results: The study of the statistical distribution of the 3D conformal radiotherapy group. In the IMRT
the 94 features among the 21 patients GTVs has been group 7 pts were female and 5 male; in the 3DCRT
useful for their comprehension. In particular, some fea- group 23 were female and 11 male. Five patients (2 in
tures appear to be inherently influenced by the volume the IMRT group and 3 in the 3DCRT group) had HIV
data, and the normalized features densities could delete positive status. In the IMRT group T stage was T2 in 9
this volume influence with a good approximation: the pts and T3 in 3 pts; in the 3DCRT group was T2 in 20
direct consequence of this is that features values and pts, T3 in 8 pts, T1 in 5 pts e T4 in 1 pts. In the IMRT
ranges are more easily comparable. The R heatmap group N stage was N0 in 5 pts and N1a in 7 pts; in the
function tool allowed a cluster analysis of the normali- 3DCRT group was N0 in 22 pts and N1a in 12 pts
zed features densities (Figure 1), suggesting a natural (AJCC, 8th edition). 4/12 pts (33%) in the IMRT group
clustering behavior, beside any clinical data, that could and 20/34 pts (58%) in the 3DCRT group interrupted
exhibit some interesting properties of two or more fea- the treatment more than 5 consecutive days due to acute
tures in highlighting some intrinsic characteristics of toxicity. IMRT treatments lead to lower incidence of
the tumour. For example, patient 3 and 7 are clustered acute toxicity events (according to RTOG scale): grade
and it can be hypothesised that their lesions have simi- 2-3 toxicity, compared to 3DCRT, reduced from 100%
lar traits. to 75% for skin, and from 35% to 25% for gastrointesti-
Conclusions: In this work a complete radiomic pro- nal toxicity. No differences were observed concerning
cess has been described by means of 3D Slicer and R complete response (RC): 8/12 pts (66.7%) in IMRT
platforms. 3D Slicer coregistration, contouring and fea- group and 22/34 (64,7%). At the last follow up 23/34
tures calculation modules have proved to be accurate pts (67%) in the 3DCRT were alive with a median fol-
and fast. Finally, it is equally important to note that 3D low up of 96 months (range 54-178); all of the patients
Slicer and R platforms offer the opportunity for small of the IMRT group were alive at the last follow up with
radiological departments to carry out radiomic analysis a median follow up of 16 months (range 7-49).
where advanced radiomics commercial softwares are Conclusions: In our experience, in anal canal carci-
not commonly available. noma, IMRT treatment has revealed equally effective
than 3DCRT but it was associated to a reduction of toxi-
city.
DP08
DP09
RADIOCHEMOTHERAPY OF ANAL CANAL
CANCER: FROM CONFORMAL THERAPY TO IMPACT OF ACCELERATED FRACTIONATION ON
INTENSITY MODULATED RADIOTHERAPY (IMRT) ACUTE TOXICITY IN PATIENTS TREATED WITH
M.E. Rosetto1, A.M. Ascolese1, M. Carcaterra1, TOMOTHERAPY FOR SQUAMOUS CELL ANAL
M.S. D'Ambrosio1, L. Mazzuoli1, A. Anitori2,
M. Russo2, M. Chilelli3, C. Signorelli3, G. Fiorentino1
CANCER (SCAC): A FREQUENCY-MATCHED
COHORT ANALYSIS
1UOC di Radioterapia; 2UOSD di Fisica Sanitaria; G. Caramia1, M. Vernaleone2, L. Visani1, P. Bonomo1,
3UOC di Oncologia – Ospedale Belcolle, Viterbo, Italy B. Meduri2, A. Galardi1, I. Desideri1, C. Becherini1,
E. D'Angelo2, P. Vasilyeva2, V. Berti3, G. Puccini3,
Aims: To evaluate the toxicity and the efficacy of F. Linguanti3, F. Lohr2, L. Livi1
Intesity Modulated Radiotherapy (IMRT) in the treat- 1Radioterapia Oncologica, Università degli Studi di
ment of squamous cell anal canal cancer.
Firenze; 2Azienda Ospedaliero-Universitaria di
Methods: A retrospective analysis has been perfor-
Modena, U.O.C. Di radioterapia oncologica; 3Unità di
med on 12 patients treated with IMRT since 2015 com-
Medicina Nucleare, Dipartimento di Scienze
paring toxicity and outcome against 34 pts treated from
Biomediche, Sperimentali e Cliniche, Azienda
2004 to 2014 with 3D conformal radiotherapy
Ospedaliero-Universitaria Careggi, Università di
(3DCRT). In most cases radiotherapy was associated
Firenze, Italy
with concomitant chemotherapy with Mitomycin C and
5-Fluorouracil (Nigro scheme), 3 patients were treated Aims: It is known from randomized studies that a
with radiotherapy alone for older age (> 80 years). prolonged overall treatment time (OTT) has a detrimen-
IMRT treatments were performed with SIB tal effect on outcome for non-metastatic SCAC. From a
(Simultaneous Integrated Boost) technique according to radiobiological point of view, a shorter OTT may be
RTOG protocol 0529 with 54 Gy in 27 fractions (2 beneficial to offset accelerated repopulation typical of
Gy/fr) to the primary tumor and lymphnodes > 3 cm, epithelial cancers, at the cost of increased morbidity.
49.95 Gy (1.85 Gy/fr) to the intermediate risk areas Tomotherapy is among the most accurate RT techniques
(lymphnodes < 3 cm) and 45,9 Gy (1,7 Gy/fr) to the low to achieve differential dose distributions with high
risk areas. 3DCRT was delivered with sequential boost: conformity. The aim of our work was to evaluate the
a dose of 45 Gy was delivered to the pelvis and a impact of an accelerated regimen (AF) on non-hemato-
median dose boost of 14.4 Gy to the primary tumor logic acute toxicity in comparison with conventional
(range 5.4-21.6 Gy). fractionation (CF).
Results: Median age of patients was 60 years (range Methods: Between May 2014 and August 2018,
46-77) in the IMRT group and 65 years (range 47-85) in patients affected by SCAC treated with Tomotherapy in

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two different institutions were considered for our study. VersaHD (TPS Monaco Montecarlo).
A frequency-matched cohort analysis was performed to Results: Two patients (A e B) had previously rece-
balance patients’ characteristics between the two groups veid initial radiation to a dose of 54 Gy in 30 fractions
(AF and CF): median age, disease stage and administra- of 1.8 Gy no reported G1-G4 toxicity; the third patient
tion of concurrent chemotherapy were the considered (C) stopped at dose of 43.2Gy, (herpetic intestizial
variables. The chosen dose/fractionation were 55 pneumonia), then he receveid first re-RT (without pro-
Gy/2.2 Gy fx and 59.4 Gy/1.8 Gy fx to high-risk CTV, gression) at dose 19.8 in 11 fraction of 1,8 Gy, reaching
45 Gy/1.8 Gy fx to low risk CTV in 25 and 33 fractions the total dose of 63 Gy. After RT all patients had an
in the AF and CF cohorts, respectively. Acute toxicity improvement of the initial symptoms and performed
was scored according to NCI – CTCAE v.4. sequential chemotherapy. At progression disease (PD),
Results: Overall, 94 subjects were included. all of them receveid re-irradiation at doses di 19.8 Gy in
Patients’ characteristics were well matched between the 11 fractions of 1.8 Gy with concomitant chemotherapy
two groups: the median age and incidence of stage II/III (nimotuzumab and vinorelbine). Interval between the
were 66 and 67 years, and 40% and 49% (TNM AJCC initial radiation therapy and Re-RT was at 6 months in
7th ed.) in CF and AF groups, respectively. In addition, A , 11 months in B and 31 months in C. The PS was 0-
concurrent chemotherapy was prescribed to 84% and 1, age from 5 to 13 years old. The Re-RT was well tole-
71% of patients, with mytomicin C-5FU as the most rated, without toxicity reported; all three patients
common regimen. The rate of > G2 radiation dermatitis, showed neurological improvement. The patient A died
diarrhea and cystitis were 73% vs. 63% (p=0.41), 18% after 4 months the RE-RT, with an overall survival (OS)
vs. 31% (p=0.22), and 11% vs. 2% (p=0.17) in CF and of 12 months, calculated from the initial radiation the-
AF cohorts, respectively. In terms of overall non-hema- rapy. Two other patients are still alive with good perfor-
tologic acute toxicity, the >G2 rate was 80% and 69% mance status. The OS, from the initial radiotherapy, of
(p=0.32), respectively. In particular, no statistically 9 months and 45 months, respectively in B and C
significant difference could be found between the two patient. The OS from the re-irradiation was 4 months in
groups. The median length of RT interruptions was 0 patient B and 14 months in patient C.
days (0-38 days). Conclusion: Based on our experience, the re-irra-
Conclusions: Our dual-institution experience diation proved to be safe in the absence of acute and/or
showed that the tolerability profile of a 5-week accele- chronic toxicity and with improvement in symptoms,
rated regimen was proved to be non-significantly worse associated with a response rate, although partial, in two
than a more prolonged regimen. Further analysis is of three patients.
ongoing to assess the impact of an AR on treatment out-
come, and to investigate the predictivity of metabolic
parameters at the baseline FDG-PET.
DP11
ABSTRACT WITHDRAWN
DP10
DP12
REIRRADIATION IN DIFFUSE INTRINSIC PONTI-
NE: SALERNO’ S EXPERIENCE STEREOTACTIC RADIOTHERAPY FOR PROSTATE
G. Scimone, D. Laslo, R. Grassi, A. Maiorana, BED RECURRENCE AFTER PROSTATECTOMY, A
L. Mastrandrea, K. Sayad, C. Scoglio, D. Di Gennaro SINGLE CENTER RETROSPECTIVE ANALYSIS
SS Radioterapia Pediatrica AOU San Giovanni di Dio e L.P. Ciccone, E. Scoccimarro, M. Aquilano,
Ruggi D' Aragona, Salerno, Italy P. Garlatti, M. Perna, G. Francolini, I. Desideri,
G. Simontacchi, B. Detti, L. Livi
Introduction: Diffuse intrinsic pontine glioma
AOU Careggi Radiation Oncology Unit - University of
(DIPG) are very aggressive neoplasm that typically
Florence, Italy
involve the pediatric age with a high recurrence rate at
short term and poor survival. Since January 2013 to Aims: This work reports the impact of Salvage
January 2019 at “SS Radioterapia Pediatrica - AOU San Stereotactic Radiotherapy (SSRT) in naïve patients
Giovanni di Dio e Ruggi d’Aragona of Salerno” recei- (pts) with Macroscopic Prostate Bed Recurrence
ved irradiation ten patients, age between 4 and 15, with (MPBR) and compares, in terms of outcome, two defi-
progressive DIPG . In this retrospective study we report nitions of Biochemical Relapse Free Survival (BRFS).
data relating to three cases of re-irradiation (Re-RT). Methods: We retrospectively reviewed the expe-
Materials and Methods: Diagnosis of DIPG was rience of AOU Careggi Radiation Oncology Unit–
achieve by biopsy in one case (A) and by imaging in the Florence between January 2014 and December 2018. In
others (B+C). All patients had performed magnetic order to better express outcome and help clinicians to
resonance imaging pre-treatment. Progression after ini- choose the correct timing of restaging after treatment,
tial chemoradiation had been confirmed clinically and two BRFS were used: BRFS1 (PSA>10% respect to
by magnetic resonance imaging. All three patients, with PSA pre-SRST) and BRFS2 (PSA increase>0.2ng/mL
PS between 1-2 and age from 5 to 10 years old, in pts with PSA nadir<0.2ng/mL or 2 consecutive PSA
underwent concomitant chemotherapy (nimotuzumab increases >25% if compared to nadir in pts with a PSA
and vinorelbine) and RT (VMAT technique) on Elekta nadir>0.2ng/mL). Kaplan-Meier survival analysis cur-

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Discussed Poster

ves (Figure 1) were performed to explore the associa-


tion between BRFS and pre-defined prognostic factors.
DP13

Results: 46 cases were collected, pts were treated


with SSRT for a total dose of 30-40Gy in 5 fractions.
DOSIMETRIC INFLUENCE OF ROTATIONAL SETUP

Median follow up was 21 months (IQR 9-39 months),


ERRORS IN VMAT RADIATION THERAPY OF PRO-

pts had a mean age of 70.78 years (63.84-77.73).


STATE CANCER
G. Rambaldi Guidasci1, D. Zefiro2, M. Piergentili2,
Gleason Score (GS) at diagnosis was >7 in 29 cases E. Verzanini2, M. Vanoli2, F. Foppiano2, T. Scolaro2
(63.04%). 54.35% (25pts) were pT3 and 95.65% 1Università degli Studi di Genova; 2ASL5 Sistema
(45pts) were N0/Nx. Risk group was high in 56.52% Sanitario Regione Liguria, Italy
(26pts). Median pre-SSRT PSA was 9.09 ng/mL (IQR
7-13). Concomitant Androgen Deprivation Therapy Aims: To evaluate the setup errors and the dosime-
(ADT) was prescribed in 18 pts (39.13%) with a median tric impact of rotations in prostate cancer radiotherapy
duration of 24 months (IQR 6-69.75). No acute or late treatment with VMAT-SIB technique.
toxicity ≥ G2 related to SRST was observed. ADT free Methods: A total of 26 patients with prostate cancer
survival rate at 1 year was 65.22% (30pts). Considering (5 low, 8 intermediate and 13 high risk) were included
BRFS1 definition, 15 pts (32.61%) had biochemical in this study. For high risk patients CTVs included the
recurrence, with a median BRFS1 time of 17 months pelvic lymph nodes. The patients underwent a moderate
hypofractionated radiotherapy (70,2 Gy/27 fr.) with
(IQR 5-25). BRFS2 definition was applicable in 20 pts
daily Image Guidance. The treatments were planned
(43,48%) with a median BRFS2 time of 16 months
with VMAT technique and performed with an Elekta
(IQR 5-23). There were any local recurrences and 10
Synergy® accelerator equipped with HexaPOD™ a
sites of distant/pelvic recurrence. Complete biochemi- robotic couch with six degree of freedom. The patient
cal response, defined as PSA nadir<0.2ng/mL, was positioning was assessed before each fraction, through
obtained in 23 (50%) pts. BRFS1 and BFRS2 were sta- the matching between the reference CT and the daily
tistically related to GS≤7 and PSA nadir<0.2ng/mL. online acquired CBCT. The rototranslational correction
Furthermore, BRFS2 were also statistically related to were applied through the robotic couch and positional
pre-SRST PSA<1ng/mL and time to MPBR>36 errors were recorded for the principal axes, left-right,
months. supero-inferior, antero-posterior, and for the rotational
Conclusions: SSRT significantly improved bioche- angles pitch, roll and yaw. The dosimetric analysis of
mical control of disease and allowed ADT delay despite the consequences of rotations was performed on a sub-
adverse features. Ablative SSRT of small recurrence group of 11 patients by manually rotating the simulation
might increase the efficacy of salvage therapy and redu- CT and the contoured structures. Using MIM
ce toxicity when compared to conventionally fractiona- Maestro®, the simulation CT was rotated around the
ted salvage irradiation to the entire prostate bed. BFRS2 isocenter by ±3° for each axis, obtaining six rotated CT
it proved to be a reliable tool to improve outcome and for each patient. The reference treatment plan was
further diagnostic-therapeutic procedures. recalculated on the new CTs and the DVHs statistics
were compared.

Figure 1. Figure 1.

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

Results: A total of 675 CBCT were retrospectively Results: Local recurrence was identified in 31% of
evaluated for this analysis. The largest magnitude for pts. The median interval between radical prostatectomy
systematic and random error was for the translation in and MPMRI was 31 mo (range, 8.3-143.7 mo). Median
the antero-posterior direction and for the pitch rotation PSA value at time of BR was 0.25 ng/mL (range 0.15-
(Figure 1). The major dosimetric changes for organs at 3.04 ng/mL in pts with positive MPMRI and range 0.10-
risk, compared to the planned doses, were observed for 0.54 ng/mL in pts with negative MPMRI). Median PSA
pitch rotation and especially for structures distant from doubling time was 7.8 mo (1.8-20.7 mo) and 7.5 mo (1.5-
the isocenter. In high risk patients the average differen- 31.1 mo) in pts with and without macroscopic recurrence
ces for V40 and V65 of rectum were ±5% and ±4% with at MPMRI, respectively. The perianastomotic site was
a maximum variation of +10%. For the bladder the the most common location of local recurrence. The
maximum difference was +4%. Femurs were more sen- median follow-up was 13 mo (0-32.3 mo); 12.5% of pts
sitive to yaw rotation with a maximum variation of the with negative MPMRI had BR, none of pts with positi-
D2%=4 Gy. With the currently used PTV margins (1 cm ve MPMRI had BR after SRT. We didn't find statistical-
isotropic margin, 6 mm to the rectum) the CTV covera- ly significant differences in clinical and pathological
ge was not affected by rotations. variables between two groups of pts.
Conclusions: In prostate cancer treatment the rota- Conclusions: Our findings suggest that MPMRI can
tional errors could cause dosimetric changes in organs identify a significant minority of patients with macro-
at risk especially when the pelvic lymph nodes are trea- scopic local recurrence. Macroscopic recurrence in pro-
ted, due to the major distance of the structures from the state bed was identified even at low PSA levels with
isocenter. Robotic couch corrections become more 33% incidence in pts with PSA <0.2 ng/mL, although
important in SBRT with high dose gradients and when numbers were limited in this subgroup. It is possible
reduced margins are used. that pts with low PSA levels and macroscopic recurren-
ce could have a better prognosis after SRT given that a
source of PSA production is identified locally.
However, longer follow-up is necessary to better under-
DP14
stand how macroscopic recurrence in prostate bed
might affect biochemical control after SRT.
UTILITY OF MULTIPARAMETRIC MAGNETIC
RESONANCE IMAGING (MPMRI) IN SALVAGE
RADIOTHERAPY PLANNING IN PATIENTS WITH
BIOCHEMICAL RELAPSE AFTER RADICAL PRO- DP15
STATECTOMY
S. Vukcaj1, G. Perugini2, R. Muni1, L. Feltre1,
SALVAGE RADIOTHERAPY GUIDED BY 68GA
F. Filippone1, M. Kalli1, L. Maffioletti1, F. Piccoli1, PSMA 11 PET/CT IN PATIENTS WITH BIOCHEMI-
M. Roscigno3, L. Da Pozzo3, S. Sironi2, CAL PERSISTENCE (BCP) AFTER RADICAL PRO-
L. Cazzaniga1 STATECTOMY FOR PROSTATE CANCER
1ASST Papa Giovanni XXIII, Radiation Oncology Unit, R. Carlevato1, R. Parise1, A. Guarneri2, S. Bartoncini2,
Bergamo; 2ASST Papa Giovanni XXIII, Radiology Unit, F. Ceci3, D. Deandreis3, E. Pilati3, P. Nicolotti3,
Bergamo; 3ASST Papa Giovanni XXIII, Urology Unit, B. Lillaz4, U. Ricardi1
Bergamo, Italy 1Department of Oncology, Radiation Oncology,

University of Turin; 2Department of Oncology,


Introduction: Patients (pts) with biochemical rela- Radiation Oncology, A.O.U. Città della Salute e della
pse (BR) after radical prostatectomy may still be cured Scienza, Turin; 3Department of Medical Sciences,
with salvage radiotherapy (SRT). To maximize chance Nuclear Medicine, University of Turin; 4Department of
for cure, irradiated volumes should completely encom- Surgical Sciences, Division of Urology, University of
pass the extent of disease. Current imaging technique Turin, Italy
has limited sensitivity for detection of macroscopic
disease in prostate bed at BR. Recently, MPMRI has Aims: Prostate cancer (PCa) patients with persistent
become more widely used and integration into routine high PSA levels (BCP) after radical prostatectomy (RP)
evaluation of prostate bed in pts with BR may improve showed less favourable survival rates. Thus, localizing
accuracy of SRT planning. residual disease after surgery is crucial to define the
Methods: Between 2017 and 2018, 35 men with BR planned target volume (PTV) of salvage radiotherapy
after radical prostatectomy underwent MRI with T2- (SRT). We evaluated the impact of 68Ga PSMA 11
weighted imaging, diffusion weighted imaging and PET/CT on SRT planning in BCP patients.
dynamic contrast-enhanced imaging, before SRT at Methods: 68Ga PSMA 11 PET/CT is performed in
Papa Giovanni XXIII Hospital, Bergamo. We perfor- our institution through a prospective, single center,
med dose escalation to the T2/DCE-MRI defined as open label study in hormone naïve PCa. We performed
high risk region by dose painting at 2.25 Gy/frx to 72 a retrospective analysis in BCP patients matching these
Gy, while the rest of CTV received 2 Gy/frx to 64 Gy. inclusion criteria: 1) RP as primary therapy; 2) PSA
In pts with negative MPMRI dose prescription was 70 nadir >0.1 ng/mL at 8 weeks after RP; 3) No
Gy/35 frx and CTV include prostatic bed. We used Chi- adjuvant/salvage therapy or hormonal therapy perfor-
Square test to identify possible relationship between cli- med after RP; 4) all patients eligible for SRT in prostate
nical, pathological and MPMRI results. bed; 5) PET scan performed within 12 months from RP.

| 115 |
Discussed Poster

Changes in clinical management and SRT planning recurrence underwent to dynamic 18F-Choline PET/CT
were defined by a multidisciplinary tumour board. and mpMRI, which revealed in all cases a local recur-
Results: Twentyeight (n=28) patients matched all rence without distant metastasis. Patients received a
inclusion criteria and were analysed. ISUP grade <=3 total dose of 80 Gy fractionated into 2Gy/die to the
(n=11/28), >=4 (n=17/28); stage >=pT3a (n=17/28); BTV. Acute and late toxicity were collected using the
pN1 (n=7/28); R1 (n=16/28). Median/mean PSA- CTC scale (vers. 4.3).
nadir=0.34/0.48 ng/mL (0.1 3.3); median/mean Results: The treatment was mostly well tolerated:
PSAdt=2.8/7.1 months (0.6 44.6); median/mean 168 patients (93%) completed treatment without any
PSAvel=0.8/3.1 ng/mL/year (range 0.1 24.7). 68Ga interruption. Acute toxicity was: Gastro-intestinal (GI)
PSMA 11 PET/CT detection rate was 57.1% (CI95% in 53 patients (29%); Genito-urinary (GU) in 35
37.4% 75.0%). Median/mean PSA at time of ima- patients (19%). No grade > 3 acute toxicity was recor-
ging=0.53/1.06 ng/mL (range 0.22 8.9). Prostate bed ded. Late toxicity was: 41 events (23%) of grade 1 GU
relapse was detected in 3.6% of cases, intra pelvic rela- toxicity and 24 patients (13%) with grade 1 GI.
pse (pelvic lymph nodes with/without prostate bed) in Nineteen patients (10%) experienced grade 2 toxicity
21.4% and extra pelvic relapse (extra pelvic nodes (nine gastro-intestinal and ten genito-urinary toxicity)
and/or bone) in 32.1%. Oligometastatic disease was and only one patient experience a grade >3 late toxicity.
detected in 53.6% of cases, in this patients SRT plan- With a median follow-up of 67 months 53/180 patients
ning was changed: 7/28 patients performed SRT in pro- (29%) experienced a biochemical recurrence.
state bed and additional stereotactic radiotherapy Conclusions: The new imaging techniques (dyna-
(SBRT) on PET positive findings. In 2/28 cases PTV mic 18F-Choline PET/CT and mpMRI) allow a better
was modified including only PET positive pelvic nodes definition of disease recurrence in these patients. With
without standard radiotherapy in prostate bed. SRT was a median follow-up greater than 5 years, high-dose SRT
aborted in 5/28 patients and ADT was administrated appears feasible and well tolerated, with low rate of late
instead. In 1/28 case SRT was aborted and pelvic lymph toxicity and promising activity.
node dissection was performed. In 46.4% of patients
(13/28), SRT was confirmed as intended before PET
scan. DP17
Conclusions: 68Ga PSMA 11 PET/CT proved its
role in BCP setting detecting disease outside prostate
MODERATE VERSUS EXTREME HYPOFRACTIO-

bed in 53.5% of cases and SRT planning was modified


NATED RADIOTHERAPY: A COMPARATIVE
due to the integration of 68Ga PSMA 11 PET/CT
ANALYSIS IN LOW AND FAVORABLE INTERME-
results. These data highlight the importance of PET
DIATE RISK PROSTATE CANCER PATIENTS
imaging in BCP setting being able to detect the presen- L. Nicosia1, R. Mazzola1, M. Rigo1, V. Figlia1, N. Giaj-
ce of disease not identified by conventional imaging. Levra1, G. Napoli1, F. Ricchetti1, G. Lunardi2,
S. Corradini3, R. Ruggieri1, F. Alongi1
1Advanced Radiation Oncology Department, IRCCS

Sacro Cuore Don Calabria Hospital, Cancer Care


DP16
Center, Negrar, (VR), Italy; 2Clinical Pharmacology
Laboratory, IRCCS-Sacro Cuore Don Calabria
THE ROLE OF MORPHOLOGIC AND FUNCTIONAL

Hospital, Negrar, (VR), Italy; 3Radiation Oncology


IMAGING (MPMRI AND 18FCH-PET/TC) IN

Department, University Hospital, LMU Munich,


DETECTION OF BIOLOGICAL TARGET VOLUME
Munich, Germany
(BTV) IN PATIENTS WITH BIOCHEMICAL RELA-

Purpose: External beam radiotherapy (EBRT) is an


PSE AFTER RADICAL PROSTATECTOMY TREATED

effective treatment option for low and intermediate risk


WITH HIGH DOSE SALVAGE RADIOTHERAPY:

prostate cancer (PCa) and it is usually delivered in con-


FEASIBILITY STUDY IN 180 PATIENTS
S. Gentile, L.E. Trodella, R.M. D’Angelillo, M. Fiore,
A. Carnevale, C. Greco, P. Trecca, M. Miele, ventional fractionation or with moderate hypofrationa-
S. Palizzi, F. Giannetti, S. Ramella, L. Trodella tion (hRT), with comparable results. In the last years, a
new treatment approach with stereotactic body
Radioterapia Oncologica,Policlinico Universitario
radiotherapy (SBRT) has shown promising results. The
Campus Biomedico di Roma, Italy
aim of the present study was to directly compare the
Aims: From 15 to 40% of patients undergoing radi- outcome and toxicity between hRT and SBRT in low-
cal prostatectomy have a biochemical relapse at five to-intermediate PCa patients.
years. Salvage radiotherapy (SRT) is the standard treat- Material and Methods: The hRT schedules were:
ment for biochemical relapse with at least 66 Gy deli- 71.4 Gy or 74.2 Gy in 28 fraction for low or intermedia-
vered to prostatic fossa. Dynamic 18F-Choline PET/CT te risk PCa, respectively, while the SBRT schedules
and mpMRI could identify site of recurrence, allowing were: 35 Gy or 37.5 Gy in 5 fractions, for low or inter-
dose escalation to a biological target volume (BTV). mediate risk, respectively. Toxicity assessment was
Methods: From January 2009 to December 2017 performed according to CTCAE v5.0 grading. The
were reviewed data of over 200 patients with biochemi- International Prostatic Symptoms Score (IPSS) was
cal progression after radical prostatectomy. One-hun- also recorded.
dred eighty patients at time of diagnosis of biochemical Results: One hundred-forty nine patients were

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L’INNOVAZIONE IN RADIOTERAPIA E IN ONCOLOGIA CLINICA: UN PONTE VERSO IL FUTURO - Rimini, 27-29 settembre 2019

analyzed, overall 81 (54.36%) patients were low risk cohorts of LAPC patients treated with EBRT +/- CT or
and 68 (45.64%) were intermediate risk. Sixty-nine SBRT +/- CT in terms of overall survival (OS), local
(46.3%) patients were treated with hypo-RT and 80 control (LC), distant metastases-free survival (DMFS),
(53.7%) with SBRT. Median follow-up was 33 months and toxicity.
(range 11-58 months). The actuarial survival rate was Methods: Eighty patients were included. Patients in
98.66%. The 3-years BFS rates were 95.5% and 100% the two cohorts were matched according to: age </≥
for hRT and SBRT, respectively (p= 0.051). One case 65years; tumor diameter < 3.0 cm, ≥ 3.0 cm and ≤ 3.9
(0.6%) of acute grade 3 urinary toxicity occurred in a cm, > 3.9 cm; cT; cN; neoadjuvant or adjuvant CT.
patient with intermediate risk treated with hRT. No dif- Median prescribed total dose was 30.0 Gy (range: 18.0-
ferences in acute, late or severe toxicity were detected. 37.5) and 54.0 Gy (18.0-63.0) for patients treated with
Conclusion: SBRT reported a good clinical outco- SBRT +/- CT and EBRT +/- CT, respectively. Toxicity
me and safe toxicity profile. Results are comparable to was evaluated by CTCAE v4.0 scale. Survival curves
hRT, but a longer follow-up is needed to assess the late were assessed by Kaplan-Meier method. For hypothesis
effectiveness and toxicity. testing, an equivalence and a non-inferiority test was
calculated.
Results: Descriptive analysis is reported in Table 1.
At univariate analysis no statistically significant diffe-
DP18

rences based on the matching criteria and acute and late


toxicities, were recorded. Median, 1-, and 2-year OS
STEREOTACTIC BODY RADIOTHERAPY +/- CHE-

were: 21.0 and 16 months, 73.8% and 79.8%, 40.1%


MOTHERAPY VS EXTERNAL BEAM RADIOTHE-

and 14.7% (p= 0.470), for EBRT +/- CT and SBRT +/-
RAPY +/- CHEMOTHERAPY: AN ITALIAN MULTI-

CT, respectively. Median, 1-, and 2-year LC were: 16.0


CENTRIC CASE-CONTROL STUDY ABOUT LOCAL-

and 22 months, 53.1% and 80.4%, 40.5% and 49.8%


LY ADVANCED PANCREATIC CANCER (PAULA-2)
A. Arcelli1, F. Bertini1, A.G. Morganti1, A. Guido1,
F. Deodato2, S. Cilla3, F. Dalla Torre2, V. Scotti4, (p= 0.017), for EBRT +/- CT and SBRT +/- CT, respec-
M.E. Rosetto5, I. Djan6, S. Parisi7, G.C. Mattiucci8, tively. Median, 1-, and 2-year DMFS were: 12.0 and
M. Fiore9, P. Bonomo10, A. Bacigalupo11, 16.0 months, 49.3% and 64.5%, 41.7% and 20.3% (p=
R.M. Niespolo12, P. Gabriele13, N. Simoni14, 0.610), for EBRT +/- CT and SBRT +/- CT, respecti-
R. Mazzarotto14, S. Cammelli1, G. Macchia2 vely. A statistically non inferiority significance in terms
1UO di Radioterapia – Dipartimento di Medicina of OS between EBRT +/- CT and SBRT +/- CT was
Specialistica Diagnostica e Sperimentale- DIMES, recorded (95% CI: 2.24, p= 0.031).
Azienda Ospedaliera-Universitaria S.Orsola-Malpighi, Conclusions: Our analysis demonstrated that SBRT
Bologna, Italy; 2Fondazione Giovanni Paolo II, UO di is comparable to EBRT in terms of clinical outcomes
Radioterapia, Università Cattolica del Sacro Cuore, and yet convenient for the patients due to its short dura-
Campobasso, Italy; 3Fondazione Giovanni Paolo II, UO tion. Therefore, our study seems to justify randomized
di Fisica Sanitaria, Università Cattolica del Sacro studies to compare SBRT +/- CT and EBRT +/- CT.
Cuore, Campobasso, Italy; 4Malzoni Radio Surgery,
Agropoli, Italy; 5Unità di Radioterapia, Ospedale
Belcolle, Viterbo, Italy; 6Institute of Oncology
Table 1.

Vojvodina, Sremska Kamenica, Medical Faculty,


University of Novi Sad, Serbia; 7Unità di Raditoerapia,
Ospedale Casa Sollievo della Sofferenza San Giovanni
Rotondo, Italy; 8Fondazione Policlinico Universitario
A. Gemelli, IRCCS, UOC di Radioterapia, Dipartimento
di Scienze Radiologiche, Radioterapiche ed
Ematologiche, Roma, Italy; 9Dipartimento di
Radioterapia, Università Campus Biomedico, Roma,
Italy; 10Dipartimento di Radioterapia, Azienda
Ospedaliero Universitaria Careggi (AOUC), Università
di Firenze, Italy; 11Dipartimento di Radioterapia,
IRCCS AOU San Martino– IST Genova, Italy; 12Unità di
Radioterapia, Azienda Ospedaliera San Gerardo,
Monza, Italy; 13Dipartimento di Radioterapia,
Fondazione del Piemonte per l'Oncologia (FPO),
IRCCS Candiolo, Torino, Italy; 14Unità di Radioterapia,
Ospedale Universitario, Verona, Italy
Aims: Chemoradiotherapy and chemotherapy (CT)
are both well-established options for locally advanced
pancreatic cancer (LAPC). Stereotactic body radiothe-
rapy (SBRT) is an emerging option for LAPC. Aim of
this multicentric case-control study is to compare two

| 117 |
Discussed Poster

DP19 DP20
POST-OPERATIVE INTENSITY MODULATED CLINICAL RESULTS AND TOXICITIES OBSERVED
RADIOTHERAPY (IMRT) IN PROSTATE CANCER: AFTER PROTON PENCIL-BEAM SCANNING OF
PEDIATRIC CNS TUMORS
B. Rombi1, A. Ruggi2, L. Ronchi3, M. Buwenge3,
A SINGLE INSTITUTE RETROSPECTIVE ANALYSIS
F. Sanna, F. Cabras, A. Carai, S. Marogna, A.R. Musu,
E. Orefici, G. Piredda, P.L. Pittau, C. Sini, M. Urpis, I. Ammendolia3, S. Cammelli3, F. Melchionda2,
S. Campoccia A. Prete2, F. Fracchiolla1, M. Zucchelli4,
Radioterapia Oncologica Ospedale San Francesco, M. Cianchetti1, S. Vennarini1, G. Morganti3,
Nuoro, Italy M. Amichetti1
1U.O. di Protonterapia, Ospedale di Trento; 2U.O. di
Aims: The aim of this study was to retrospectively Pediatria, Dipartimento della salute della donna del
analyse genitourinary (GU) and gastrointestinal (GI) bambino e delle Malattie Urologiche, Azienda
toxicities in a single institute cohort of patients (pts) Ospedaliera-Universitaria S.Orsola-Malpighi;
treated with moderate hypofractionated or conventio- 3Dipartimento di Radioterapia – DIMES (Dept. of
nally fractionated post-prostatectomy radiotherapy. Experimental, Diagnostic and Specialty Medicine)
Methods: From September 2011 to May 2016, 63 Azienda Ospedaliera-Universitaria S.Orsola-Malpighi;
post-operative pts with localized prostate cancer 4Neurochirurgia pediatrica, Ospedale Bellaria, Italy
underwent adjuvant (n=49) and salvage (n=14) IMRT.
Of the 63 pts, 16 pts (25,4%) received prophylactic Aims: we report the clinical results and toxicities in
lymph-nodal irradiation . IMRT was delivered at con- 16 children with various CNS tumors treated with pro-
ventional (CF: 1,8-2 Gy/fr, n=27) or moderate hypo- ton pencil-beam scanning.
fractionated (HYPO: 2,3 Gy/fr, n=36) fractionation Methods: between 2015 and 2019, 16 patients
scheme. The total dose ranges to the prostatic bed were (M/F: 10/6; median age 6 years [13 mo-17 yrs]) with
64-70 Gy and 59.8-68.2 Gy for CF and HYPO group of CNS tumors received proton therapy (PT), 12 of whom
pts, respectively. Pelvic lymph-nodes were always trea- with daily anesthesia: 8 medulloblastomas (MB; 3 stan-
dard, 5 high risk), 2 pilocytic astrocytomas, 3 Atypical
ted with conventional fractionation (50.4 Gy, daily
Teratoid/Rhabdoid Tumors (AT/RTs), 1 pure germino-
dose: 1.8 Gy/fr). A two-tailed t-test was performed to
ma, 1 choroid plexus carcinoma (CPC) and 1 invasive
assess statistical difference between CF and HYPO
meningioma. All patients received surgery (3 total, 10
groups. Toxicities was graded according to Common
partial resections or near total resection, 3 biopsies) and
Terminology Criteria for Adverse Events (CTCAE),
15/16 received chemotherapy: 9 before PT with 5
version 4.0.
hematopoietic stem cell transplantations (HSCT), 2
Results: Median overall follow-up (FU) was 35 both before and after PT and 4 after PT. Toxicity was
months (range 16-74). At the end of radiotherapy, 13/63 graded using the Common Terminology Criteria for
(20.6%) pts showed acute Grade ≥2 urinary toxicity, Adverse Events (CTCAE) v4.0. Median total dose was
5/27 (18.5%) and 8/36 (22.2%) in conventionally frac- 54 CGE (1.8 daily fractions).
tionated RT and hypofractionated RT, respectively. Results: at a median follow-up of 20 months [5-43
Eight pts (8/27; 29.6%) and 9 pts (9/36 ; 25%) reported mo] all patients are alive, 8 with a complete response
acute Grade ≥2 GI for CF and HYPO cohort, respecti- (CR) and 6 with stable disease (SD). Two patients expe-
vely. Six pts (6/27; 22.2%) and three pts (3/36; 8.3%) rienced progression (PD): one with a diencephalic
showed late Grade ≥2 GU in the CF and HYPO group. AT/RT showed 10 months after a 1st PT to the primary
Late Grade ≥2 GI were reported in 2/27 pts (7.4%) in site a distant relapse, that was treated with chemothe-
the CF group and 2/36 (5,6%) in the hypofractionated rapy, HSCT and proton craniospinal irradiation (CSI)
group. Only 1 late Grade 4 urinary toxicity was reported with CR; one with PA had an increase of both cystic and
in the CF group of pts. No Grade 4 acute or late GI/GU solid residual tumor 10 months after PT. Hematological
in the hypofractionated group was observed. No signi- toxicity was mild, no transfusions were necessary; only
ficant correlation between toxicity and fractionation 4 cases of G3 neutropenia were seen in patients who
scheme was found. received CSI at 36.0 CGE (3 of them received HSCT
Conclusions: In the post- operative setting, a mode- before PT). The other >G2 acute/subacute toxicities
rate hypofractionated radiotherapy resulted well tolera- were: 1 G3 PRES, 1 G3 perilesional brain edema, 1 G3
ted in our cohort of patients. Rate of grade ≥2 late toxi- fatigue and 1 G3 headache; 3/4 recovered completely,
city in the hypofractionated group was lower than in CF 1/4 partially. Late toxicities were as follows: 1 MB
group, but this difference was not statistically significa- patient had a self-limiting intracranial bleeding (G2) 24
tive. months after PT (on that site, the total dose was 54.0
CGE); the AT/RT patient who received PT twice deve-
loped 15 months after the 1st PT an asymptomatic
Moya-Moya-like arteriopathy (G1; local dose of 54.0
CGE) and 2 patients (1 CPC, 1 MB) developed asymp-
tomatic cavernomas (G1; both had received 36.0 CGE
CSI) 21 and 9 months after PT, respectively.

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Conclusions: our experience shows that PT can be a of correlation with Picci grade (p=0,072), even without
viable option for radiotherapy of pediatric CNS tumors, statistical significance. 26 (96,3%) patients had FDG
showing good disease control and only limited toxicity. PET/CT after induction chemotherapy before surgery.
However, longer follow-ups and higher patient numbers Median SUV2 was 0 (range 0-7.1). Median metabolic
are needed to draw conclusions on long term results and response was 100% (range 31,11%-100%). At statisti-
toxicities. cal analysis SUV2 is related with PFS (P<0,0001).
Considering SUV distribution, at Wilcoxon test for pai-
red samples all SUV values decrease with treatment.
Only in one patient SUV2 was not inferior to SUV1; in
DP21
this case SUV1 at diagnosis was low.
Conclusions: FDG PET/CT is an effective and
THE ROLE OF FDG PET/CT TO PREDICT RESPON-

noninvasive approach to assess response to induction


SE TO INDUCTION CHEMOTHERAPY IN EWING

chemotherapy in EWS patients. SUV1, SUV2 and


SARCOMA
D. Dei, E. Scoccimarro, C. Ciabatti, P. Garlatti,
metabolic response values could be useful in predicting
D. Greto, S. Scoccianti, B. Agresti, G. Beltrami,
chemotherapy resistance and in selecting patients with
A. Tamburini, V. Briganti, L. Livi
a more aggressive disease to risk adapted treatments
Radiation Oncology Unit, Department of Biomedical, before surgery but the role of FDG PET/CT needs to be
Experimental, and Clinical Sciences, University of further investigated in future trials.
Florence, Azienda Ospedaliero Universitaria Careggi
(AOUC), Florence; Radiation Oncology Unit -
Department of Biomedical, Experimental, and Clinical
Sciences, University of Florence, Azienda Ospedaliero
DP22

Universitaria Careggi (AOUC), Florence; Department


ANALYSIS OF 6D COUCH COMPENSATIONS IN
of Orthopaedic Oncology and Reconstructive Surgery,
VOLUMETRIC MODULATED ARC THERAPY
University of Florence, Azienda Ospedaliero
(VMAT): OUR EXPERIENCE IN 248 PATIENTS
Universitaria Careggi (AOUC), Florence; Hematology- V. Nardone1, I. Guida2, M. Mormile1, D. Borrelli1,
Oncology Unit, University of Florence, Azienda S. Maffei1, M. Gaetano1, F.M. Giugliano1,
Ospedaliero Universitaria A. Meyer, Florence; Nuclear S. Guerriero2, S. Cappabianca2, C. Guida1
Medicine Unit, University of Florence, Azienda 1Unit of Radiation Oncology Ospedale del Mare,;
Ospedaliero Universitaria Careggi (AOUC), Florence, 2Department of Precision Medicine University of
Italy Campania Luigi Vanvitelli, Napoli, Italy
Aims: Histological response to induction chemothe- Aim: To evaluate the compensations of a positio-
rapy is an important prognostic factor in patients with ning system with six degrees of freedom (lateral, longi-
Ewing sarcoma (EWS). The role of FDG PET/CT in tudinal, vertical, pitch, roll and yaw) in the radiation
predicting response remains unclear. The aim of our treatment of various diseases.
study was to assess the prognostic value of quantitative Methods: We progressively analyzed 248 patients
indices derived from FDG PET/TC performed at base- treated with Volumetric Modulated Arc Therapy
line and after induction chemotherapy. (VMAT) at our Radiation Therapy Unit from
Methods: We retrospectively collected data from September 2018 till April 2019, for a total of 2810 frac-
EWS patients treated at our Institution between 2008 tions. During the set-up of each fraction, patient ana-
and 2017 who performed FDG PET/CT at diagnosis tomy from planning CT was aligned through cone beam
and after induction chemotherapy +/- neoadjuvant CT (CBCT) by a Clinician and 6D movements were
radiotherapy, before surgery. All patients underwent executed, so that we collected the couch compensa-
surgery of the primary tumor after induction chemothe- tions. Among these patients 68 were treated for prosta-
rapy. We evaluated the primary tumor SUVmax at base- te, 58 for head and neck, 48 for brain, 28 for lung, 20
line (SUV1), the SUVmax after induction chemothe- for gynecological district, 18 for rectum, 8 for breast
rapy (SUV2) and the metabolic response calculated as tumours. Mean values and standard deviations were
[(SUV1-SUV2)/SUV1]x100. The correlation of meta- calculated for all sites. We considered as statistically
bolic response with Histologic response according to significant a couch compensation >0.5 cm (lateral, lon-
Picci grading system was also assessed. gitudinal and vertical) and >1° (pitch, roll and yaw).
Results: Twenty-seven patients were included. Results: Considering all the patients, mean absolute
Median age was 13 years (range: 4-67). Primary EWS values are as follows: 0.253 cm lateral, 0.231 cm longi-
was bone-located in 23 patients (85,2%) and derived tudinal, 0.31 cm vertical, 0.76° pitch, 1.072° roll,
from soft tissue in 4 patients (14,8%). Median SUV1 0.924° yaw. According to the different disease, the
was 6.2 (range 2.1-13.5). In 21 (77,8%) patients mean values differ significantly, with the head and neck
SUV1≥4 and in 6 (22,2%) was <4. 14 (51,8%) patients tumor showing the lower compensations (respectively
received preoperative radiotherapy. After surgery a <2% and <28% showing compensations >0.5 cm and
II/III Picci grade necrosis was achieved in 16 patients >1°) and the lung cancer showing the higher compensa-
(59,3%). At univariate statistical analysis stage of disea- tions (respectively <37% and <60% showing compen-
se correlated with progression free survival (PFS, sations >0.5 cm and >1°).
p=0,025). In patients with SUV1≥4, SUV1 had a trend Conclusion: Adjustments in six dimensions, inclu-

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Discussed Poster

ding unconventional pitch, roll and yaw rotations, Regarding the HPV status, 16/31 (51%) were HPV/p16
improve the patient set-up in all treatment sites, but positive. Globally, 8/31 (26%) patients had smoked for
seems to be especially important in the treatment of more than ten pack-years. All patients were treated
lung cancer patients. with RT +/- Cht according to guidelines. At the univa-
riate analysis the median local progression-free survival
(LPFS) was 75 months (range 22-85 months). The
median LPFS according to HPV-status was 22 and 75
months for HPV- and HPV+ patients, and the 2-year
LPFS was 42.8% and 83.9% for HPV- and HPV+
patients, respectively (p=0.01; HR 3,5725, i.c. 0,91-
13,94). The median distant progression-free survival
(DPFS) was 75 months (range 27-85 months). The
median DPFS stratified for HPV-status was 22 and 85
months, and the 2-year DPFS was 48.5% and 92.3% for
HPV- and HPV+ patients, respectively (p=0.01; HR
4.0028, i.c. 0.86-18.56). The ROC analysis showed that
no semi-quantitative tumor and nodal metabolic para-
meters before irradiation was correlated to LPFS and
DPFS.
Conclusion. In our experience HPV status remains
Figure 1.

the only predictive factor of local response and distant


DP23 progression in OPC.

SEMI-QUANTITATIVE METABOLIC PARAMETERS


DP24
IN OROPHARYNGEAL CANCER UNDERWENT
RADICAL TREATMENT: PREDICTIVE ROLE FAC- THE PREDICTIVE POWER OF MAGNETIC
TORS OF RESPONSE? A MONO-INSTITUTIONAL RESONANCE IMAGING IN IDENTIFYING THE
PATHOLOGICAL GRADING OF MENINGIOMAS
E. D’Ippolito1, F. Ballati2, C. Paganelli3, A. Iannalfi1,
RETROSPECTIVE STUDY
R. Mazzola, G. Napoli, J. Doraku, V. Figlia,
N. Giaj-Levra, L. Nicosia, M. Rigo, F. Ricchetti, G. Buizza3, G. Viselner4, A. Bacila5, L. Farina5,
M. Salgarello, F. Alongi P. Lomoro2, R. Petrucci1, S. Ronchi1, M. Bonora1,
Advanced Radiation Oncology Department, IRCCS M.R. Fiore1, B. Vischioni1, V. Vitolo1, G. Baroni3-6,
Sacro Cuore Don Calabria, Negrar (VR), Italy L. Preda4-7, F. Valvo1
1Division of Radiotherapy, National Center of
Aim. The role of pre-treatment semi-quantitative Oncological Hadrontherapy (CNAO) Pavia;
metabolic parameters was herein analyzed, as potential 2Department of Diagnostic Medicine Institute of
predictors of Local Control (LC) and distant progres- Radiology, IRCCS San Matteo University Hospital
sion free-survival (DPFS) in Oropharyngeal cancers Foundation, Pavia; 3Department of Electronics,
(OPC). Information and Bioengineering, Politecnico di Milano,
Methods. Inclusion criteria of the present retrospec- Milano; 4Diagnostic Imaging Unit, National Center of
tive study were: 1) age >18 years old; 2) histologically Oncological Hadrontherapy (CNAO) Pavia;
proven HPV positive or negative OPC; 3) patients 5Department of Neuroradiology, IRCCS Istituto
underwent definitive Intensity Modulated RT+/- Neurologico Casimiro Mondino, Pavia;
Chemotherapy; 4) pre-treatment FDG PET/TC perfor- 6Bioengineering Unit, CNAO, Pavia; 7Department of
med in the Medicine Nuclear Medicine of our Clinical-Surgical, Diagnostic and Pediatric Sciences,
Institution; 5) patients affected by early or locally University of Pavia, Italy
advanced disease by means of FDG PET/TC. The fol-
lowing semi-quantitative metabolic parameters on pri- Aims: To assess whether Magnetic Resonance
mary tumor and nodal disease were retrospectively Imaging (MRI) is able to predict the histological WHO
analyzed: (1) standardized uptake value or SUV-max; grading of meningiomas and in particular if it is able to
(2) SUV-mean; (3) metabolic tumor volume (MTV), differentiate WHO I from WHO II and WHO III
tumor volume with a SUV ≥3, threshold 40%; (4) total Methods: 76 histologically proven meningioma
lesion glycolysis (TLG), i.e. the product of SUV-mean patients with 77 lesions undergoing particle-therapy
and MTV. LC was defined as absence of local failure were enrolled in the study (43 WHO I, 27 WHO II, 7
(primary tumor and nodal disease). DPFS was defined WHO III). MRI data were acquired before treatment
as the interval between the end of RT and the diagnosis (Siemens Verio 3T) based on T1 and T2- weighted MRI
of distant metastases. and diffusion (DWI) MRI. T1 were used to delineate
Results. According to the inclusion criteria, thirty- tumor, whereas DWI to derive multi-parametric ima-
one OPC patients were included for the analysis. The ging features based on conventional ADC and Intra-
median follow up was 16 months (range, 6-90 months). Voxel-Incoherent-Motion (IVIM) model (i.e. ADC, D,
Patients median age was 65 years old (range, 39-80). D*, f). Median ADC, D, D* and f values were compu-

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ted within tumor volume. Morphological variables of extracted and selected for the predictive model defini-
the meningiomas were also considered: tumor localiza- tion following an iterative method ad-hoc developed for
tion, T1- and T2- signal intensity relative to grey matter, this study. Fifteen different classifiers were trained on
shape, tumor-brain interface, peritumoral edema, this dataset: the training set was then partitioned in five
capsular enhancement and tumor enhancement after folds and the training process was repeated in cross-
intravenous injection of gadolinium. validation for three times. Model selection was carried
Results: Regarding the DWI parameters, median out using the Area Under the Curve (AUC) of the
values of ADC, D, D* resulted higher for WHO I than Receiving Operator Characteristic (ROC) curve as tar-
WHO II and WHO III and, by grouping together WHO get metric.
II and WHO III, statistically significant differences Results: A total of 183 pts were analysed and divi-
were observed with respect to WHO I in D and D* ded in a 156 pts training set from site A and a 27 pts
(p<0.05). Also, statistically significant differences external validation set from site B. The model showing
(p<0.05) were found between WHO I and WHO II/III the highest performance was the random forest
in terms of morphological features such as tumor loca- (RF_DEF) initialized with the default parameters, with
lization, T1- and T2- signal intensity relative to grey an AUC of 0.76 on the training set and 0.82 on the
matter, tumor shape, peritumoral edema, capsular external validation set, as reported in Figure 1.
enhancement, tumor enhancement, while the presence Conclusions: Radiomics appeared to be a reliable
of tumor-brain interface did not demonstrate a statisti- tool in the prediction of pCR for LACC pts undergoing
cally significant difference between the two groups. NACRT, supporting the identification of patient’s risk
Conclusion: Preliminary results show that both group and allowing to tailor treatments according to the
image-derived and morphological features could be predicted outcome. The technical robustness of the
potential predictors of meningioma histological grade. model and its encouraging AUC values offer clinicians
In future these features may be useful to characterize an innovative tool of clinical decision support, omics
lesions with no histological diagnosis and for applica- based treatment guidance and personalization.
tion in tailored particle therapy treatments.

DP25
ABSTRACT WITHDRAWN

DP26
MR-BASED RADIOMICS MODEL FOR TREATMENT
RESPONSE PREDICTION AFTER NEOADJUVANT
CHEMORADIOTHERAPY IN PATIENTS AFFECTED Figure 1. ROC curve for internal and external validation.
BY LOCALLY ADVANCED CERVICAL CANCER
A. Pesce1, R. Autorino2, L. Boldrini2, J. Lenkowicz1,
D. Cusumano2, N. Dinapoli2, B. Gui2, L. Russo1,
G. Ferrandina1-2, G. Macchia3, G. Sallustio3,
DP27

M.A. Gambacorta1-2, R. Manfredi1-2, V. Valentini1-2


VULCAN STUDY 1.0 - THE ROLE OF ADJUVANT
1Università Cattolica del Sacro Cuore, Rome;
RADIATION THERAPY IN THE MANAGEMENT OF
2Fondazione Policlinico Universitario A. Gemelli VULVAR CANCER
IRCCS, Rome; 3Fondazione Giovanni Paolo II, A. D’Aviero1, L. Tagliaferri2, G. Garganese2,
Università Cattolica del Sacro Cuore, Campobasso, G. Macchia3, C. Casà1, V. Lancellotta2, B. Fionda2,
Italy B. Gui2, G. Perotti2, S. Gentileschi2, F. Inzani2,
G. Corrado2, A.G. Morganti4, V. Valentini1-2,
Aim: To investigate the potential role of MRI radio- G. Scambia1-2, M.A. Gambacorta1-2
mics to predict pCR following neoadjuvant chemora- 1Università Cattolica del Sacro Cuore; 2Fondazione
diotherapy (NACRT) in patients (pts) with locally Policlinico Universitario A. Gemelli IRCCS;
advanced cervical cancer (LACC) before therapy starts. 3Fondazione Giovanni Paolo II, UO di Radioterapia,
Methods: Patients with LACC (FIGO IB2-IVA) Università Cattolica del Sacro Cuore; 4Radiation
with a 1.5 T staging MRI were considered for this mul- Oncology Centre, Department of Experimental,
ticentric analysis. All patients underwent NACRT with Diagnostic and Specialty Medicine, University of
concomitant weekly cisplatin, followed by radical sur- Bologna, Italy
gery. Pathological response to treatment was assessed
on surgical specimen and defined as absence of any Aims: Multidisciplinary clinical approach should
residual tumour after treatment in any site. Patients’ be evaluated to offer personalized treatment strategy in
images were divided into a training (site A) and an inde- patients with vulvar cancer, a rare disease accounting
pendent external validation set (site B) and underwent 0.6% of women malignancies. Adjuvant External Beam
radiomics analysis. A total of 1889 features were Radiotherapy (EBRT) +/- Chemotherapy (CT) can be

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Discussed Poster

administered in presence of high-risk factors. VULvar 24 months the OS was respectively 100% and 95.8%
CANcer Multi-Disciplinary Team (Vul.Can MDT) was while DFS was respectively 87.5%, 83.3%. For patients
settled in 2013 in Policlinico Universitario A.Gemelli without positive nodes at 12- and 24 months OS was
IRCCS, in order to propose tailored treatment strategies 100% and 90.9%. No grade 4 toxicity was reported, 4
for vulvar cancer patients. The aim of this work is to patients (13%) experienced G3 acute cutaneous toxicity
update the Vul.Can MDT experience in the manage- while 1 patient (3%) showed G3 late cutaneous toxicity;
ment of adjuvant EBRT. no other G3 toxicity occurred.
Conclusions: Our experience show as multidiscipli-
nary approach can help in personalizing the manage-
ment of adjuvant treatment of vulvar cancer. Data of our
experience confirms that in patients with high-risk
Table 1. Vul.Can MDT internal recommendation for adjuvant radiotherapy in Vulvar

Vulvar Cancer adjuvant EBRT+/-CT is safe and has an


Cancer and schedules for dose delivery.

effective impact in preventing local relapse and impro-


ving OS.

DP28
ANALYSIS OF ACUTE AND LATE TOXICITY IN
LOCALLY ADVANCED HEAD AND NECK CANCER
PATIENTS TREATED WITH HYPOFRACTIONATED
SIB-IMRT
F. Sanna, F. Cabras, A. Carai, S. Marogna, A.R. Musu,
E. Orefici, G. Piredda, P.L. Pittau, C. Sini, M. Urpis,
S. Campoccia
Radioterapia Oncologica Ospedale San Francesco,
Nuoro, Italy
Aims: To report the acute and late toxicity in a
cohort of patients (pts) treated with a moderate hypo-
fractionated Simultaneous Integrated Boost Intensity
Modulated Radiation Therapy (SIB-IMRT) for locally
advanced Head and neck squamous cell carcinoma
(HNSCC).

Table 1.

Methods: Retrospective analysis of data vulva can-


cer patients treated in adjuvant setting from April 2013
to September 2017 was conducted. Adjuvant EBRT+/-
CT was performed according to the internal protocol
and recommendations proposed by Vul.Can MDT in
high risk patients defined by margin status, tumor inva-
sion and nodal involvement. EBRT was administered
with doses between 50 Gy-60 Gy to perineum and 45
Gy to negative nodal regions; patients with pathological
positive nodes received EBRT doses between 45 Gy-60
Gy. Patients after 2015 were treated using IMRT
(Simultaneous Integrated Boost) and EBRT was perfor-
med with bolus. Concomitant CT schemes were
Cisplatin and 5-Fluorouracil (PlaFuR) or weekly
Cisplatin. Toxicity was revealed in regular follow-up
using CTCAEv4.
Results: Data of 35 patients were analyzed, with a
median FUP time of 32 months (6-72 months).
Concomitant CT was performed in 15 patients, 20
patients underwent exclusive EBRT. At 12- and 24 Methods: From 2011 to 2017 at Radiation
months overall survival (OS) was respectively 96.9%, Oncology of San Francesco Hospital, 70 pts affected by
and 94%, while the Disease-Free Survival (DFS) was locally advanced HNSCC were treated with SIB-IMRT
90% and 77%. In patients with positive nodes at 12- and with or without concomitant chemotherapy. Median age

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was 60 years (range 43-86), 83% males, 17% female nasopharyngeal disease were treated in our institution
and ECOG PS 0-2. The primary tumor sites were 40% and received three cycles of induction chemotherapy
oropharynx, 23% larynx, 17% hypopharynx, 7% oral with cisplatin-5Fluorouracil followed by concomitant
cavity, 6% unknown primary cancer, 4% nasopharynx, radiochemotherapy treatment like TREP protocol.
3% others; 98% (69 pts) squamous cells cancer; PET- Treatments were performed with Tomotherapy on the
staged 67% IV a-b, 19% III, 10% II, 4% I (AJCC-7 th primary tumor and bilateral laterocervical lymphonodes
edition). 52 pts received SIB-IMRT with concurrent with a total dose of 63 Gy in 35 fractions.
CDDP-based chemotherapy or cetuximab (51 and 1 Results: Late toxicity was assessed according to
respectively) and the remaining pts underwent SIB- CTCAE 5.0 scale. Reported late effects were: G1 pho-
IMRT alone. The prescribed 3 level of doses were tosensitivity skin, G1 xerostomia, G1 hearing impaired,
67.5Gy (2.25Gy/fr), 60 Gy (2Gy/fr), 54 Gy (1.8Gy/fr) G1 skin fibrosis and periodontitis with loss of dental
for the high risk PTV, intermediate risk PTV and low elements despite recommendations for oral hygiene and
risk PTV respectively in 30 fractions (one fraction supportive therapy with fluoride. At 19 months follow-
daily) in 40 days. Pts were examined once a week up, 35 months and 37 months respectively all patients
during radiation treatment, after 1, 3, 6 and 9 months, are alve with complete response.
then every 6 months up to 5 years. Toxicity was graded Conclusions: Multimodal therapy of children with
using Common Terminology for Adverse Events nasopharyngeal carcinoma is associated with long-term
(CTCAE) Version 4.0. The median follow-up of survival. It is expected that further advances in the
patients still alive was 21 months (range 4-96). management of these patients, with improved radiothe-
Results: 96% of patients completed the treatment. rapy and chemotherapy, will achieve better quality of
The following severe acute toxicities were observed: life for treated children. IMRT-IGRT treatments in
17% G3 skin reactions, 17% G3 mucositis, 9% G3 and tumors have allowed a dose saving in organs at risk and
6% G4 dysphagia, 16% G3 hematological toxicity (all a consequent reduction in late toxicity.
with concurrent chemotherapy). One patient died
because of fatal bleeding during radiotherapy. The fol-
lowing late severe toxicities were observed: 1% G3
DP30
xerostomia, 3% G3 and 7% G4 dysphagia. No chondro-
necrosis of the larynx was observed (Table 1). Patients
REPEATED COURSES OF STEREOTACTIC RADIO-

who experienced any severe acute toxicity were 3 G3


SURGERY (SRS) FOR INTRACRANIAL OLIGO-

and 1 G4 in RT alone and 22 G3 and 4 G4 in CRT group


PROGRESSIVE METASTASES USING A NON-

respectively. Patients who experienced any severe late


COPLANAR MONO-ISOCENTER LINAC-BASED

toxicity were 1 G3 and 2 G4 in RT alone and 7 G3 and


DELIVERY TECHNIQUE (HYPERARC™) VERSUS
3 G4 in CRT group respectively.
UPFRONT WHOLE-BRAIN RADIOTHERAPY
Conclusions: Moderate hypofractionation for local-
(WBRT): A MATCHED-PAIR ANALYSIS
ly advanced HNCC has substantial benefits for patient- L. Nicosia1, V. Figlia1, G. Napoli1, M. Rigo1,
centric care, including shorter treatment duration, and R. Mazzola1, F. Ricchetti1, N. Giaj-Levra1,
reduced travel time. Moderately accelerated chemo- R. Ruggieri1, F. Alongi1,2
1Advanced Radiation Oncology Department, IRCCS
IMRT is safe and feasible with good compliance and
acceptable acute and late reactions. Sacro Cuore Don Calabria Hospital, Cancer Care
Center; 2Radiation Oncology Department, University of
Brescia, Brescia, Italy
Introduction: Brain metastases (BMs) are a major
DP29
LATE TOXICITY IN IMRT-IGRT TREATMENT OF cause of cancer death from many solid tumor and are
associated to a poor survival. SRS or stereotactic frac-
tionated radiotherapy (SFRT) is an effective treatment
NASOPHARYNX IN THE PEDIATRIC AGE:

option in multiple BMs management. Modern techni-


EXPERIENCE OF A SINGLE CENTER
G. Terranova, A. Palmeri, A.Gioia, G. Trapani,
E. Quartuccio, G. De Gregorio, A. Donofrio, ques allow the delivery of multiple SRS courses in case
V. Valenti, A.Tripoli, G. Evangelista, G. Mortellaro, of subsequent intracranial progression, nevertheless lit-
A. Lo Casto tle is known regarding the effectiveness and the toxicity
Università degli studi di Palermo, Italy when compared to WBRT. Through a retrospective
matched-pair analysis, we compared a series of patients
Aims: Nasopharyngeal carcinoma is a rare tumor in affected by limited BMs (≤10) from solid tumors trea-
children with an incidence of 1/100000. It originates ted with multiple SRS/SFRT courses using a mono-iso-
from epithelial cells of the nasopharynx. Risk factors center non-coplanar technique (HyperArc™ Varian
include: EBV infection, environmental factors such as Medical System) or WBRT.
nitrosamines and genetic factors. Diagnosis occurs in Material and Methods: Between July 2017 and
10% of cases when the disease is locally advanced and January 2019, 44 total multiple treatment courses
metastases are present. Current care protocols manage accounting for 201 metastases treated with
excellent prognosis with overall survival above 85%. HyperArc™, were evaluated in 19 patients and matched
Methods: Form 2015 to 2017, three children aged with 38 patients treated with WBRT. This latter techni-
11-15 years with locally advanced (stage III) que was the standard of choice before the implementa-

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Discussed Poster

tion of HyperArc™ at our Institution in July 2017. which necessity of a Standardized Data Collection
Matching criteria were life expectancy >3 months, (SDC) for generating evidences was highlighted. For
performance status, primary tumor histology and BMs this reason, a project focusing on breast cancer was
number. Median BMs number was 4 (range 2-10) for developed.
HyperArc™ and 5 (range 2-10) for WBRT. The Median
RT dose in the Hyperarc™ population was 25 Gy
(range 20-25 Gy) for SRS and 25 Gy in 3-6 fractions
(range 18-30 Gy) for SFRT. RT dose in the WBRT
Table 1. Timeline framework for ATTM.BLADE project.

population was 30 Gy in 10 fractions. Overall survival


(OS) and toxicity were evaluated.
Number of Phase Description of Phase

Results: Median follow-up was 9 months (range 1- 1 Multidisciplinary Team Creation


18 months). Median OS was 10 months for HyperArc™ 2 Literature and Guidelines review
patients and 7 months for WBRT patients, the 12 month 3 Ontology development
OS was 77% and 34.6% for HyperArc™ and WBRT, 4 Ontology validation
respectively (p=0.001; HR4.77, I.C.: 1.62-14). One 5 Organization of Ontology according to Open Clinica’s Criteria
case of radionecrosis occurred in a patient 12 months 6 Ontology uploading into BOA system
after the first SRS course. 7 Interface validation
Conclusion: HyperArc™ is an effective and safe
technique for the treatment of multiple BMs. Further
subsequent courses can be safely delivered in selected
cases of intracranial oligoprogression. SRS showed
improved survival when compared to WBRT, in
patients with a limited number of BMs.

DP31
THE ASSISI THINK TANK MEETING BREAST
LARGE DATABASE FOR STANDARDIZED DATA
COLLECTION IN BREAST CANCER TUMOR –
ATTM.BLADE
F. Marazzi1, V. Masiello1, C. Masciocchi1,
M. Meluzzi2, P. Belli3, L. Boldrini1, D. Capocchiano1,
Figure 1. Extract of sample analysis after uploading of BC post-mastectomy
G. Franceschini4, M.A. Gambacorta1, S. Magno4,
radiotherapy patients uploading for usage test.
E. Meldolesi1, F. Moschella4, A. Mulé5, D. Smaniotto1,
D. Terribile4, R. Masetti4, P. Poortmans6, C. Aristei2,
Material and Methods: The BLADE project consi-
V. Valentini1
sted in a multiphase workflow for development of SDC
1Fondazione Policlinico Universitario A. Gemelli
system for breast cancer research. Standardized langua-
IRCCS, UOC di Radioterapia Oncologica, ge ontology, platform for sharing data, inferential and
Dipartimento di Diagnostica per Immagini, machine learning statistic were elaborated for suppor-
Radioterapia Oncologica ed Ematologia, Roma, Italy;  ting creation of Decision Supporting Systems (DSSs) in
2Università di Perugia e Ospedale Generale di Perugia,
breast cancer treatment (Table 1). The study methodo-
Unità di Radioterapia Oncologica, Perugia, Italy; logy protocol was approved by Ethical Committee of
3Fondazione Policlinico Universitario A. Gemelli
Fondazione Policlinico Gemelli IRCCS with Prot N.
IRCCS, UOC di Diagnostica per Immagini, 0043996/18 on October 2018. A data entry and an enge-
Dipartimento di Diagnostica per Immagini, neer performed a usage test with a database of patients
Radioterapia Oncologica ed Ematologia, Roma, Italy; treated with post-mastectomy radiotherapy.
4Fondazione Policlinico Universitario A. Gemelli
Results: BLADE project developed a system in
IRCCS, UOC di Chirurgia Senologica, Dipartimento di which a validated semi-formal ontology with 630 rele-
Scienze della Salute della Donna e del Bambino e di vant variables was defined from a consensus between a
Sanità Pubblica, Roma, Italy; 5Fondazione Policlinico panel of experts. Variables were organized in 6 Case
Universitario A. Gemelli IRCCS, UOC di Anatomia
Report Forms (CRFs) according to OpenClinica's
Patologica, Dipartimento di Scienze della Salute della
Criteria. Privacy protection was guaranteed thanks to
Donna e del Bambino e di Sanità Pubblica, Roma, Italy;
6Radiation Oncology, Institut Curie, Department of distributed learning technology. The usage test on 72
pts confirmed the potentials of the system in terms of
Radiation Oncology; Paris Sciences & Lettres - PSL
privacy protection, coherence of data collection and
University; Paris, France
possibility to analyzed them. In Figure 1 is reported a
Background: In clinical practice and multicentre frame of statistical analysis on these database test. The
research purposes, a shared large database and data pri- system allow inferential statistics for testing large num-
vacy control are mandatory. In Assisi Think Tank ber of variables (even from PACS or treatment plan
Meeting (ATTM) 2016 a team of radiation oncologists, DVHs).
expert in breast cancer care, elaborates a statement in Conclusion: A validated SDC system, promoted by

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ATTM, has been created for supporting breast cancer distribution is shifted 0.5 mm toward the surface; no
care. Further multicentre use can implement the system dosimetric difference were detected between FF and
itself and promote creation of DSSs from big data with FFF. The estimated dose delivery time with VMAT-FFF
the aim of personalizing treatments. approach is 7 seconds for each of the two arcs.
Conclusions: DIBH improves heart and LAD spa-
ring significantly minimizing the high doses. VMAT
FFF is an attractive option considering the reduction of
DP32
VOLUMETRIC MODULATED ARC THERAPY delivery time in DIBH.
(VMAT) WITH FLATTENING FILTER FREE (FFF) IN
DEEP INSPIRATION BREATH-HOLD (DIBH) DP33
VERSUS FREE BREATH (FB) FOR ADJUVANT
LEFT-SIDED WHOLE BREAST RADIOTHERAPY CLINICAL IMPLEMENTATION OF DIBH WITH OPTI-
(RT): A PLAN COMPARISON STUDY CAL SYSTEMS FOR LEFT-SIDED BREAST CAN-
E. Ferrara1, G. Loi2, I. Manfredda1, V. Burgio1, CER: PRELIMINARY RESULTS
E. Gallizia1, E.Mones2, C. Perotti1, M. Krengli1,3 F. Maurizi1, F. Palleri2, C. Blasi1, A. Ciarmatori2,
1Radioterapia Oncologica, AOU Maggiore della M. Mazza1, E. Argazzi2, G. Capezzali1,
Carità; 2 Fisica Sanitaria, AOU Maggiore della Carità, S. Giancaterino2, M. La Macchia1, G. Moroni1,
Novara; 3Dipartimento di Medicina Traslazionale, M. Mariselli2, M. Bono2, F. Bunkheila1
1UOC Radioterapia Oncologica, Az. Osp. Ospedali
Università del Piemonte Orientale, Italy
Riuniti Marche Nord; 2UOC Fisica Medica e Tecnologie
Aims: To evaluate the potential dosimetric benefits Biomediche, Az. Osp. Ospedali Riuniti Marche Nord,
of DIBH in terms heart sparing and to compare the Italy
performances of different techniques for left-sided
whole breast RT. Aims: Adjuvant radiotherapy (RT) is a crucial part
Methods: Ten patients (pts) planned for post-opera- of multimodal management of breast cancer patients
tive RT (50Gy/25fractions) were included. Two CT- (pts). In this setting, late cardiac toxicities that can be
scans were acquired for each pt, one in FB and one in induced by breast RT are now recognized as rare but
voluntary DIBH. All pts were instructed to deeply relevant sequelae. Deep inspiration breath hold (DIBH)
inspire and hold the breath for 15 seconds with audio technique can reduce cardiac dose in whole breast irra-
coaching, tracking the breathing signal with the Varian diation (WBRT). In the present study, the implementa-
RPM (real-time position management) system to assess tion of DIBH using surface monitoring systems is
the reproducibility. The clinical target volumes were described.
contoured both on FB and DIBH scans. Three different Methods: Patient selection included women under-
techniques were carried out and compared both on FB going WBRT for breast cancer with at least 1 of the fol-
and DIBH CT scans: a plan based on tangential parallel lowing characteristics: age ≤50 years (ys), cardiac
opposed fields modulated with step and shoot intensity diseases, previous cardio-toxic chemotherapy regi-
modulated radiotherapy (IMRT), the same technique mens. The respiratory gating systems used were optical
with sliding window IMRT, a VMAT approach with surface scanning devices: Sentinel for simulations and
two opposed mini-tangential arcs. VMAT-DIBH plans Catalyst HD for treatments (C-Rad). Simulations were
were calculated using both flattening filter free (FFF) performed with pts positioned supine on wing or breast
and Flattering filter (FF) 6 MV beams. Planning was boards with both arms raised above the head. The
performed using the treatment planning system (TPS) patient training was carried out by providing women
Raystation with robust optimization. A phantom was with electronic eyeglasses (video coaching) where they
used to verify the dosimetric equivalence of the diffe- can see their breathing signal. Only pts able to follow
rent techniques in terms of dose delivered to the skin. the training to find their individual deep inspiration
Results: Regarding the reproducibility of contours level and to retain breathing for almost 20s have been
on FB and DIBH scans, not significant differences were selected. Finally, a DIBH CT scan was taken. All pts
found in terms of planning target volumes (PTVs) were also studied in free breathing (FB) in order to
(p=0.25) and heart (p=0.26). Left lung volumes increa- compare the dose distribution for PTV and OARs. Thus
sed in DIBH (p<0.,001). No significant differences contouring and 3D conformal treatment planning were
were shown in the PTVs coverage with the different realized and evaluated on both CT studies. The prescri-
techniques in terms of D95 (p=0.97), dose homogeneity bed dose was 40Gy (15 fx) to the whole breast +/- 10Gy
(p=0.95) and conformity (p=0.35). A slightly increase boost to the tumour bed.
in hotspots (D2) for the VMAT FFF (p=0.02) were Results: Of 55 evaluated pts, 14 pts were screened
found. A significant reduction of maximum dose D2 according to the selection criteria, 2 pts withdrew, 2 pts
(p=0.0003) to the heart, maximum (p=0.0002) and were excluded due to their inconstant breathing, 10 pts
mean dose (p=0.0006) to the left anterior descending were selected (age:46-69ys) and 9 pts successfully
coronary (LAD) were found. LAD dose reduction is completed the DIBH treatment. Comparison of FB and
related to heart to lung volumes ratio on FB SCAN. The DIBH treatment plans in all pts confirmed the DIBH
planning technique had no impact on dose distribution able to reduce heart mean dose by ~50% and heart D2cc
to the PTVs and OARs. For VMAT treatments dose by 15-85%. The analysis of the entire process of DIBH

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Discussed Poster

shows a certain increase of time for some procedures:


patient training, doubled contouring and treatment plan-
DP35

ning and longer delivery.


Conclusions: The DIBH technique was successfully
EVALUATION OF LONG-TERM CARDIAC MORTA-

implemented and resulted a safe and feasible treatment


LITY EXCESS RISK IN LEFT-SIDED BREAST

strategy. Despite the small sample size and the prelimi-


RADIOTHERAPY: A COMPARISON BETWEEN

nary analysis, DIBH provides better treatment quality


VMAT AND FIELD-IN-FIELD (FIF) TECHNIQUE
L. Grimaldi, F. Rottoli, V. Morandini, S. Berlinghieri,
due to the cardiac dose sparing. Considering workforce E. Castrezzati, L. Spiazzi, P. Frata, N. Pasinetti
requirements and time commitments, clinical correla- Department of Radiation Oncology, ASST Valcamonica,
tions of the DIBH dosimetric benefits with the reduc- Esine, Brescia, Italy
tion in cardiac mortality are expected.
Aims: In left breast radiotherapy, late cardiac dama-
ge is the most important side effect to be kept under
strict control. The purpose of this paper was to compare
DP34
the risk of long-term cardiac mortality between a stan-
dard FIF technique and VMAT.
IRREGULAR SURFACE COMPENSATOR TECHNI-
QUE FOR POSTOPERATIVE BREAST RADIOTHE-
RAPY: EVALUATION OF ACUTE SKIN TOXICITY
A. Di Donato, P. Falco, E. Ippolito, S. Silipigni,
A. Carnevale, GM. Petrianni, S. Palizzi,
L. Trodella, S. Ramella
Università Campus Bio-Medico di Roma, Italy
Background: The irregular surface compensator
(ISC) is an electronic compensator and a kind of
forward planning IMRT (FP-IMRT) that allows signifi-
cant improvements in dose distribution in whole breast
radiotherapy (WBRT) compared with the traditional
field-in-field (FIF) technique. The aim of this study is to
evaluate acute toxicity of patients treated with ISC
WBRT technique.
Material and Methods: The prevalence of moist
desquamation among patients treated with 3D radiothe-
rapy in the current literature is about 25%. To achieve
80% power to reduce the rate of moist desquamation to
15% or less a minimum of 132 patients were needed.
Prescribed dose to the breast was 50 Gy in 25 fractions.
Patients with negative prognostic factors received a
tumor bed boost of 10 Gy in 5 fractions. Toxicity was
assessed using the Common Terminology Criteria for
Adverse Events.
Results: 185 consecutive patients received ISC
WBRT technique. Ninety-nine (53.5%) patients were
left sided, 86 (46.5%) right sided. One hundred eleven
(60%) patients received tumor bed boost. Median age
was 64 (range=33-95). Median PTV cc was 643.6
(range=112.29- 1984.4). Grade 1 dermatitis occurred in
48.6%. The incidence of moist desquamation was
15.1%. Only in three patients, all with breast CTV cc Materials: Data from 18 female patients undergoing
greater than 1500 cc, the moist desquamation area was left breast radiotherapy were evaluated, for which the
greater than 2 cm. Eight patients (4.32%) suspended estimate of long-term cardiac mortality, with the relati-
radiotherapy course (median days= 6 ; range=4-8). ve serial model, had a range from 0.5% to 9% with the
Conclusions: ISC WBRT technique was associated FIF technique. Two treatment plans were optimized for
with a lower rate of moist desquamation compared with every patient, one with FIF technique (2Gy/fr x 25fr,
literature reported rate of 3D-WBRT. Therefore, this boost 2Gy/fr x 5fr) and one with VMAT (1.8Gy/fr x 28
technique seems to confirm in a clinical setting the dose fr, SIB 2.1Gy/fr x 28 fr).The schedules were chosen to
distribution advantages showed in planning studies. keep, as possible, the same BED values both on the tar-
get and on the heart tissues. EQD2 was calculated for
each heart absorbed dose distribution and the Relative
Seriality model (α/β=3Gy, s=1, D50=52.4Gy and
g=1.28) was used as method to evaluate the probability

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of late cardiac mortality. doses was for lung metastases 48 Gy/4 fx, for bones
Results: The use of VMAT technique leads to an metastases was 20 Gy/4 fx. Ten pts receveid immu-
increase in low doses to the heart but a significant notherapy concurrent at RT, 14 pts within 2 weeks after
reduction in high dose peaks which, according to the the end of RT; 6 pts performed before immunotherapy
relative serial model, are responsible for the increase in and after RT. All pts continued immunotherapy every 2
the value of long-term cardiac mortality. Moreover, weeks thereafter until progression disease or unaccepta-
VMAT technique allows a better dose distribution to the ble toxicities. The primary endpoint was the occurrence
PTV and the Conformity Index (COIN) is greater than pneumonitis or other non-hematological toxicity; the
30%. LADCA (Left Anterior Descending Coronary secundary endpoint was local control and progression-
Artery) absorbed dose is less than 60% if VMAT tech- free survival. The toxicities was evaluated according
nique is adopted. The average of the ratios between the RTOG scale.
probability of long-term cardiac mortality with VMAT Results: Grade 3 pneumonitis occurred in 1 patient,
technique vs FIF in the 18 patients was 0.027 (min for which hospitalization has been requested. Fatigue in
0.001; max 0.133). Paired data t-Student test showed a 15 pts and fever in 3 pts, no endocrinological toxicities
statistical significant differences between the two sets has been reported. Follow-up time was 26 months and
of data (p<0.001) were recorded: 4 complete response and 7 partial
Conclusions: VMAT technique seems to be safer responses after 6 months after the end radiotherapy, 7
than FIF in terms of probabilities of risk of late heart progression disease outside the radiation field after 5
damage. The probabilities evaluated in this work are the months of immunotherapy, 10 pts continued immu-
result of a calculation and are closely related to the irra- notherapy. In 2 pts recorded worsening of PS-ECOG
diation technique used and targeted at specific end- after 8 months of immunotherapy.
points. During the optimization of the treatment plan, Conclusions: PD1 and PDL-1 inhibitors with hypo-
attention is needed to check for the hot-spots dose, fractionated radiation therapy is a treatment safe and
especially when a hypofractionated scheme is adopted. feasibility. There is still no gold standard in treatment
Every dose distribution should be evaluated in terms of sequencing. In all schedules the treatment was well
EQD2 and the radiobiological DVHs should be evalua- tolerated and we had a good local control.
ted alongside physical ones. For this reason, modern
TPSs should promote, even more, the use of either
radiobiological DVHs or algorithm optimization.
DP37
EFFECT OF POLY(ADP-RIBOSE) POLYMERASE-1
DP36 INHIBITION ON HUMAN SOFT TISSUE SARCOMA
CELLS RADIOSENSITIVITY: IN VIVO STUDY
HYPOFRACTIONATED RADIOTHERAPY WITH PD1 V. Lorenzetti1, M. Mangoni1, M. Sottili1, G. Salvatore1,
AND ANTI PDL-1 IN OLIGOMETASTATIC NSCLC: C. Ciabatti1, S. Lucidi1, P. Garlatti1, M. Lo Russo1,
SAFETY AND FEASIBILITY C. Talamonti1, G. Beltrami2, D. Campanacci2,
G. Acquaviva1, M. Tamburo1, A. Tocco1, G. Corsaro1, D. Greto1, L. Livi1
D. Marletta2, F. Arena2, F. Privitera2, F. Marletta1 1Dipartimento di Scienze Biomediche, Sperimentali e
1UOC Radioterapia-AOE Cannizzaro di Catania; Cliniche, Università di Firenze; 2Dipartimento di
2Sc. di spec. in Radioterapia-Univ. di Messina, Italy Ortopedia oncologica, Azienda Ospedaliera
Universitaria Careggi, Firenze, Italy
Aims: Five-year survival rates for metastatic non
small cell lung cancer (NSCLC) is < 5%. Radiotherapy Aims: Soft-tissue sarcomas (STS) are malignant
is an option of treatment in these setting of patients and tumors with a poor prognosis and limited therapeutic
is often given concurrently or sequentially with che- options. Poly-ADP ribose polymerase (PARP)-1 is a
motherapy. Related chemotherapy toxicity often wor- DNA-binding protein, activated by nicks in the DNA
sens adherence to radiation treatment, hence the need to molecule, who play a role in DNA strand repair. Some
perform less toxic systemic therapies such as immu- STS have defects in DNA repair, so PARPi may be used
notherapy. Radiationtherapy (RT) might modify the to kill these cells selectively. Previous studies demon-
cancer immune enviroment to enhance the antitumor strated that PARPi can inhibit DNA damage repair
effect of immune checkpoint inhibitors. We analyzed when used in combination with irradiation, reducing
NSCLC metastatic pts treated with hypofractionated cell survival. The aim of this study was to investigate
radiotherapy and PD1 and PD-L1 inhibitors. The pri- the effect of PARP inhibition in a xenograft model of
mary endpoint was safety and feasibility, secondary rhabdomyosarcoma in mice after tumor cells irradia-
was local control and progression free survival. tion.
Methods: From December 2016 to February 2019 Methods: Rhabdomyosarcoma cells were irradiated
we have retrospectively examined 30 pts with lung with 3 Gy, with or without a pre-treatment with 24
(n.10 pts) and bones metastases (n.20 pts) from hours olaparib (1 µM) . The control was made with non-
NSCLC, chemotherapy pretreated. The inclusion crite- irradiated cells. Four group of mice were compared:1)
ria were oligometastatic pts, after chemotherapy-failu- control; 2) olaparib; 3) irradiation; 4) irradiation+olapa-
re. All pts were treated with anti PD1/PDL-1 and hypo- rib. Rhabdomyosarcoma xenograft was obtained by s.c.
fractionated RT to the disease sites. The prescription injection of 6×106 cells in the flank of CD1 nude mice.

| 127 |
Discussed Poster

Twice a week tumor volume was measured, for a period patient during whole brain RT who was symptomatic
of 30 days, by the formula [lenght x(width x width)]/2. before radiotherapy and successfully treated with
Immunofluorescence and western blotting analysis Levitaceram and mannitol. We observed two radione-
have been performed. crosis (10%) occurring at 2 months and 4 months after
Results: In comparison to control group olaparib the end of stereotactic RT. One of these two latter
alone reduced tumor growth, but without reaching a sta- patients was treated with WBRT followed to several
tistical significance. Moreover, a significant reduction stereotactic radiotherapy treatments at different time-
of tumor volume was shown with irradiation alone rela- points, while the other was treated to 6 lesions with ste-
tive to control. The association of olaparib and irradia- reotactic radiotherapy at the same time. We observed no
tion showed an even higher decrease in tumor volume significant difference in acute neurological toxicity
compared to irradiation alone, reaching the statistical between patients who received whole brain RT or ste-
significance vs. irradiation or olaparib alone after 8 reotactic RT. Additionally, there was no difference in
days. The mean immunofluorescence of gamma H2AX AE rates on the basis of timing of ICI administration
on rhabdomyosarcoma cells was significantly increased with respect to RT. With a median follow up was 6
after treatment with olaparib and with radiation alone; a months (range 1-16 months), 16 patients (80%) were
higher intensity of fluorescence was obtained with com- evaluable for response: 5 (31.25%) had brain progres-
bined treatment. Tumor growth was inversely propor- sion after stereotactic RT, 5 (31.25%) had stable disease
tional to the mean immunofluorescence of gamma after stereotactic RT, 3(18.75%)complete response after
H2AX. With western blotting analysis we observed that stereotactic RT and 3 (18.75%) partial response after
irradiation increased the level of phosphorylated-active whole brain RT. 6 patients (30%) died during follow up
ERK1/2 (p44/42 MAPK) compared to the control. The for extracranial disease progression and 1 patient (5%)
add of olaparib to irradiation significantly reduced the will have MRI in the next few months.
irradiation-induced phosphorylation of ERK1/2. Conclusions: Treatment with an ICI and cranial RT
PCNA, involved in DNA repair pathway. seems feasible. However dose escalation in these
Conclusions: In this study we showed that olaparib patients may be at risk of increased radionecrosis.
have a synergic therapeutic effect with irradiation on Additional studies on larger series are needed.
rhabdomyosarcoma xenograft, with significant reduc-
tion of tumorigenesis, confirming previous studies in
vitro. This results encourages future research about this
DP39
association. HYPOFRACTIONATED IRRADIATION IN ELDERLY
BREAST CANCER PATIENTS: AN OBSERVATIO-
NAL STUDY
E. La Rocca1,2, M. Dispinzieri1,2, E. Meneghini3,
DP38

A. Fiorentino4, F. Bonfantini5, S. Di Cosimo6,


COMBINED IMMUNE CHECKPOINT INHIBITORS
AND ENCEPHALIC RADIOTHERAPY: M. Gennaro7, V. Cosentino5, M. Sant3, E. Pignoli5,
ACUTE AND LATE TOXICITY EVALUATION R. Valdagni1,8, L. Lozza2, M.C. De Santis2
P. Matteucci, B. Santo, E. Ippolito, S. Silipigni, 1University of Milan, Department of Oncology and
P. Zuccoli, S. Palizzi, M. Fiore, L. Trodella, S. Ramella Hemato-Oncology; 2Fondazione IRCCS Istituto
Università Campus Biomedico, Roma, Italy Nazionale dei Tumori, Radiotherapy Unit 1;
3Fondazione IRCCS Istituto Nazionale dei Tumori,
Aims: Immune checkpoint inhibitors (ICIs) have
Analytical Epidemiology and Health Impact Unit;
shown highly promising responses in solid tumors. 4Regional General Hospital F Miulli, Radiation
Intracranial metastases are frequently managed with
Oncology Department; 5Fondazione IRCCS Istituto
radiation therapy (RT). The safety of cranial RT in the
Nazionale dei Tumori, Medical Physics Unit;
setting of treatment ICIs has not been established. We 6Fondazione IRCCS Istituto Nazionale dei Tumori,
aimed to assess acute and late toxicity in patients trea- Department of Applied Research and Technological
ted with cranial RT and anti programmed cell death- Development DRAST; 7Fondazione IRCCS Istituto
1(PD-1). Nazionale dei Tumori, Breast Surgery Unit; 8
Methods: We identified patients with brain metasta- Fondazione IRCCS Istituto Nazionale dei Tumori,
ses from different primaries, who received cranial RT Director, Radiation Oncology 1 and Prostate Cancer
and were concurrently treated with anti PD-1. RT-rela- Program, Italy
ted AEs were evaluated and analyzed according to ICI
treatment status, cranial RT type, and timing of RT with Aims: To assess efficacy, acute and late toxicity of
respect to ICI. hypofractionated radiotherapy (Hypo-RT) and impact
Results: Between July 2017 and May 2019 20 of age and comorbidities in elderly breast cancer (BC)
patients with advanced solid tumors were treated: 15 patients (pts).
(75%) Non Small Cell Lung Cancer (NSCLC), 3 (15%) Methods: From June 2009 to December 2017 we
melanoma, 1 (5%) Sarcomatoid tumor of the lung and 1 analyzed 808 pts receiving 42.4 Gy in 16 daily frac-
(5%) renal cell carcinoma. Fifteen (75%), 2 (10%), and tions. A boost was administered in cases of grade 3 pri-
3 (15%) patients received stereotactic RT, whole brain mary tumor and close/positive margins. Acute and late
RT or both, respectively. We observed seizures in one toxicity was prospectively assessed, based on the

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RTOG scale. Baseline comorbidities included in the months symptomatic and local control, which could be
hypertension-augmented Charlson Comorbidity Index insufficient for long term survival oligometastatic
(hCCI) were retrospectively retrieved. Five-year disea- patients (pts). Recent studies demonstrated long term
se-free survival (DFS) and overall survival (OS) were pain and local control by dose intensification delivered
assessed by Kaplan-Meier method and log-rank test with stereotactic body radiotherapy (SBRT). The aim of
was used to compare groups of age and comorbidity. this study is to evaluate clinical effectiveness and safety
Hazard ratios (HRs) were estimated by Cox proportio- of SBRT using Cyberknife in spinal and bone metasta-
nal hazards models adjusting for tumor size, lymph ses.
node status, molecular subtype, grading, chemotherapy. Material and Methods: From October 2017 to May
Odds ratios (ORs) of acute and late toxicity by of age, 2019, 71 pts with 94 oligometastatic/oligoprogressive
comorbidity and boost administration were estimated spinal and bone metastases were treated with
by ordinal or multinomial logistic models. Cyberknife in our Institution: 78.7% were spinal
Results: The median age was 74 years (range 65-91 lesions, while 21.3% was non-spine. The most common
years), and 76.1% of the pts were over 70. The median histology was prostate cancer 62.8%, followed by brea-
follow-up was 46.8 months (range 4-115 months). At st 11.7%, kidney 7.4%, lung 6.4%, bladder 4.3%, rectal
baseline, 70.4% of pts were affected by at least one 3.2%, pancreatic 2.1%, ovarian 1.0%, and uterine cer-
comorbidity. Invasive ductal carcinoma was the most vix cancer 1.1%. Pain was present before SBRT in 32%
common histological type (81.2%), and the most com- of pts with a median value of 5 (3-8), according to
mon subtype was luminal A (46.5%). 21.5% of the pts Visual Analogue Scale (VAS). Two mg of dexametha-
underwent chemotherapy. At the latest follow-up date, sone were prescribed in 51% of pts for 1 week. In 80%
90.4% pts were still alive, 5.8% experienced disease of pts with spinal lesions, to maximize tumor coverage
progression (relapses, contralateral BC, metastases), 18 and minimize spinal cord exposure, a simulation CT a
died of BC and 60 died of other causes. DFS was 92.6, T1 and T2 MRI were fused and used to outline the gross
87.2, 83.5 and 71.3% for 65-69, 70-74, 75-79 and ≥80 tumor volume (GTV). GTV to planning target volume
years, respectively (p<0.001). OS for increasing age- (PTV) expansion was 2 mm. Median dose prescription
class was 94.7, 93.0, 86.7 and 80.9% (p=0.002). Five- was 18 (16-35) Gy, delivered in a median of one frac-
year DFS and OS were 91.9% and 94.3% for pts tion (1-7).
without comorbidity and 74.3% and 84.5% for pts with Results: Median follow-up was 5 (1-17) months.
hCCI≥2 (DFS p<0.001, OS p=0.017).Elderly pts had Early pain relief was observed in all symptomatic pts.
significantly higher odds of increasing score in acute Local progression occurred in 5.3% of pts with a
asthenia. Pts with hCCI≥2 had significantly increased median time to local failure of 2.42 (1-3) months.
odds of late edema and fibrosis. Boost administration Median total dose of pts presenting progression at fol-
was significantly related to acute skin toxicity and late low up CT/MRI was 27 (18-27) Gy, delivered in a
fibrosis and edema. median of 3 (1-3) fractions. The histology of progressi-
Conclusions: Hypo-RT in elderly BC pts is effective ve tumors were colon cancer, bladder cancer and uteri-
and well-tolerated. This study shows that age and ne cervix cancer. One patient developed G2 acute pain
comorbidities negatively impact DFS and OS. Further flare toxicity (according to CTCAEv4.03), after one
studies focusing on a better selection of elderly BC pts day of dexamethasone suspension. The pain was con-
based on genomic and biological features and with tai- trolled prolonging dexamethasone for two additional
lored treatment approaches are warranted. days. In 66 lesions with a follow up longer than 3 (3-17)
months, no late toxicities and SBRT-related fractures
were observed.
Conclusions: Our experience with dose intensifica-
DP40
tion in spinal or bone metastases matches with the
published studies, which demonstrated that vertebral
STEREOTACTIC BODY RADIOTHERAPY AS DOSE

and bone SBRT is a safe treatment providing a low


INTENSIFICATION FOR BONE AND SPINAL META-

acute and late toxicity and early pain relief in all pts. A
STASES: A RETROSPECTIVE MONOISTITUTIONAL
longer follow up is necessary to confirm the very good
ANALISYS
C.T. Delle Curti1,2, A. Sanchez Galvan1,2, F. Borroni1,2, local control.
R. Tummineri1,2, A. Fodor1, C.L. Deantoni1,
F. Zerbetto1, S. Broggi3, B. Longobardi3, S. Arcangeli2,
N.G. Di Muzio1
1Department of Radiotherapy, San Raffaele Scientific

Institute, Milano; 2Department of Radiotherapy,


University Milano Bicocca; 3Medical Physics, San
Raffaele Scientific Institute, Milano, Italy
Aim: The treatment of spine and bone metastases
with standard external beam radiotherapy ensures a six

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Poster

Poster

weekly and by three months from the end of RT, for


acute toxicity (according to CTCAE version 4.03).
PO001

Results: Among the 193 pts treated, 140 have never


been repositioned (72,54%), 29 pts have been repositio-
EVALUATION OF ACUTE GENITOURINARY AND

ned once (15,03%), 4 pts have been repositioned more


GASTROINTESTINAL TOXICITY IN PATIENTS

than three times and only 1 the maximum number


TREATED WITH VOLUMETRIC INTENSITY

recorded (n=8). Among 95 pts in the post-operative set-


MODULATED / IMAGE-GUIDED RADIOTHERAPY

ting , acute GU toxicity recorded were: G0=12,63%,


(VMAT/IGRT) FOR PROSTATE CANCER
E. Villa, M. Motta, A. Ravasio, R. Gualano,
V. Manazzale, D. Gherardi, P. Ghirardelli, V. Vavassori G1=49,47%, G2=37,74% and G3=3,16%; more impor-
tant toxicity were nocturia (G3 in 3 pts and G2 in 28
U.O. Radiotherapy, Humanitas Gavazzeni, Italy pts) and urinary frequency (G2 in 14 pts), Acute GI and
Aims: The introduction IGRT-IMRT allows an rectal toxicity was mild with G2 as a maximum grade in
improvement of precision and accuracy in the treatment 4 patients (diarrhea in 2 pts, hemorrhoids and inconti-
of patients (pts) with prostate cancer. To reduce prostate nence in 1 pts respectively), and none G3. Of 98 pts
displacemnts during the dose-delivery we introduce a treated with radical intent, acute GU toxicity recorded
written protocol for reproducible filling bladder and were G0=6,12%, G1=37,76%, G2=46,94% and
empty rectum. The study aims to evaluate the complian- G3=9,18; more important toxicity were nocturia (G3 in
ce to this protocol and the acute genito-urinary (GU) 8 pts and G2 in 32 pts) and urinary frequency (G3 in 3
and gastrointestinal (GI) toxicity. pts and G2 in 30 pts). Acute GI and rectal toxicity was
Methods: We analyzed 193 consecutive pts (98 with G2 in 7 pts (diarrhea in 3 pts, hemorrhoids in 2 pts,
radical intent and 95 in the post-operative setting) trea- hematochezia and tenesmus in 1 pt respectively), and
ted for prostate cancer from 2017. Patients were treated G3 in 2 pts.
with moderate hypofractionated VMAT/IGRT (28-30 Conclusions: According to our results, moderate
fractions) on prostate and seminal vesicles (2.5 Gy/fx) hypofractionated RT (also in the post-operative setting)
or prostate bed (2.2-2.25 Gy/fx), +/- pelvis nodes (1.8 seems to be feasible and safe, with a good toxicity pro-
Gy/fx) and +/- ADT. All pts were treated with empty file. Moreover we recorded a good compliance to pro-
rectum and full bladder, according to a written protocol tocol for reproducible filling bladder and empty rectum,
Daily set-up control with CBCT was conducted and the useful tool for the reproducibility of treatment and dose
number of repositioning due to inadequate preparation delivering to target and OARs.
were recorded. During treatment pts were evaluated

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PO002
BILATERAL HIP PROSTHESES AVOIDANCE
TECHNIQUE IN THE TREATMENT PLANNING FOR
A CASE OF ENDOMETRIAL ADENOCARCINOMA
A. Di Rito1, R. Carbonara1, M. Bettiol2, S. Bonaduce1,
A. Milella1, A. Nardone1, R. Necchia1, A. Pascali1,
G. Scognamillo1, N. Perna2, V. Didonna2, M. Lioce1
1UOC Radioterapia IRCCS Istituto Tumori Giovanni

Paolo II; 2UO Fisica Sanitaria IRCCS Istituto Tumori


Giovanni Paolo II, Italy
Aims: Hip prosthetic implants - usually made of
high density material - attenuate the incoming radiothe-
rapy (RT) treatment beams and scatter the dose, with
subsequent dosimetric uncertainty at the soft tissue
interfaces and in the evaluation of dose uniformity insi-
de the planning target volume (PTV). Furthermore, arti-
facts on images are usually caused by prostheses.
Therefore, a standard practice is the avoidance of these
prosthetic materials in the treatment planning. We
report the case of an endometrial adenocarcinoma
occurred in a patient with bilateral hip prostheses trea-
ted with a technique of hip prostheses avoidance (HPA).
Methods: A 76-years old woman with bilateral hip
prostheses and an history of left breast cancer (2003)
treated with mastectomy, chemotherapy, radiotherapy
and hormonal therapy, underwent in 2018 surgery
(hysteroannessectomy) for uterine prolapse: the histolo-
gic diagnosis was endometrioid adenocarcinoma G3
with no endovascular invasion, pathological stage
pT1bNx. An external beam RT treatment plan with bila-
teral HPA was implemented. A total dose of 50 Gy in 25
fractions was prescribed to pelvic nodes and tumor bed,
followed by a HDR-brachytherapy boost on the vaginal
cuff (10 Gy in 2 fractions).
Results: At first, a contouring of the artifacts gene-
rated by the hip prostheses was done to assign them the
water density. The HPA plan was implemented with a
mixed technique: a VMAT technique for the upper
region of PTV and a 3D conformal RT technique with 5
static beams (three obliques and two AP/PA beams) to
cover the lower regions of PTV. VMAT and 3D beams
had the same isocenter, to shorten the treatment time
and to avoid unfavorable overlap. A good target covera-
ge was achieved: V95 was 98%, Homogeneity Index
(Dmax/Prescription dose) was 1.04. A satisfactory
dose-sparing of the organs at risk (OARs) was also
obtained. Imaging with daily KV was scheduled.
Figure 1.

Monitor Units were 248 + 458, the overall time for


treatment delivery was 2 minutes and 20 seconds. Low
grade acute toxicity (diarrhea G1) was observed. A
Computed Tomography performed three months after
the completion of RT confirmed absence of disease. No
late adverse event was reported.
Conclusions: We propose a technique for HPA plan-
ning to allow good target coverage and HI, with an ade-
quate sparing of OARs. Short delivery times and an
adequate image-guidance support patient’s compliance
and treatment accuracy.

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Poster

still long term potential toxicity. The use of state-of-art


treatment planning and delivery modalities could play
PO003

an important role to improve quality of life and survival


in lymphoma patients, however no guidelines in IMRT
ATTITUDES AND PRACTICE TOWARDS INTEN-

dose constraints have been published. According to


SITY-MODULATED RADIATION THERAPY TECHIN-

most of AIRO Radiation Oncologists participating to


QUES IN THE TREATMENT OF MEDIASTINAL

this survey, a manuscript on specific dose constraints


LYMPHOMAS: A NATIONWIDE, MULTICENTER

for ML radiotherapy should be published.


SURVEY BY ASSOCIAZIONE ITALIANA DI RADIO-
TERAPIA ED ONCOLOGIA CLINICA (AIRO) AND
FONDAZIONE ITALIANA LINFOMI (FIL)
A. Di Russo1, S. Meregalli2, M. Buglione Di Monale3,
E. Bastia3, P. Ciammella4, G. De Marco5, V. De
PO004

Sanctis6, A.R. Filippi7, B. Lanfranchi5, M. Levis8, HELICAL TOMOTHERAPY IN THE TREATMENT OF


S. Vagge9, U. Ricardi8, G. Simontacchi10 UNFIT BLADDER CANCER PATIENTS: A MONO-
1SC Radioterapia Oncologica 1, Fondazione IRCCS INSTITUTIONAL STUDY UPDATE (2011-2018)
Istituto Nazionale dei Tumori di Milano; 2SC F. Pastore, A. Rese, F. Cammarota, D. Toledo,
Radioterapia, Ospedale San Gerardo, Monza; M. Conte, G. Ciaglia, V. Iorio
3Radioterapia Oncologica Spedali Civili, Università di Fondazione Muto ONLUS, Casavatore (NA), Italy
Brescia; 4Radioterapia Oncologica Usl-Irccs Reggio
Emilia; 5Uoc Radioterapia AOU Policlinico Modena; Aims: To evaluate the use of Helical Tomotherapy
6Radioterapia Oncologica, AO Universitaria S. Andrea, (HT) in the treatment of bladder cancer. The HT system
Università La Sapienza Roma; 7Fondazione IRCCS employs a compact 6 MV Linac-based on CT ring gan-
Policlinico S. Matteo, Pavia; 8Dipartimento di try to rotationally deliver intensity modulated fan
Oncologia, Università di Torino; 9UOC Radioterapia beams. Patients are translated through-out the gantry on
Oncologica, IRCCS Ospedale Policlinico San Martino, a treatment couch, resulting in helical irradiation geo-
Genova; 10UO Radioterapia, Dipartimento di metry. The HT unit also contains a mega-voltage CT
Oncologia, AOU Careggi, Firenze, Italy detector array located opposite the radiation source for
pre-treatment verification, allowing accurate re-positio-
Aims: To report the results of a nationwide, multi- ning. This technique permits to precisely target tumors
center survey investigating the practice of Intensity- while minimizing impact on surrounding healthy tissue:
Modulated Radiation Therapy (IMRT) techniques in the this could be very interesting for unfit bladder patients,
treatment of mediastinal lymphomas (ML). to reduce GU and GI toxicity.
Methods: In October 2018, a 25-items questionnaire Methods: 38 patients (age: 51-89) with bladder can-
was sent to all Italian Radiation Oncology Departments cer were treated in our institution from 2011 to 2017
on behalf of Fondazione Italiana Linfomi (FIL). with HT. None of these patients were fit for surgical
Centers were asked to provide data on the use of IMRT indication due to concomitant medical conditions. None
techniques in the irradiation of ML (HL and NHL), col- of these patients had concomitant chemotherapy due to
lecting specific information about radiation treatment medical conditions. 21/38 (55%) of these patient had
prescription and delivery. positive lymphonodes. CT axial scanning was perfor-
Results: 43/195 Centers completed the survey. The med at 5-mm intervals: for this purpose a CT Multislice
median amount of irradiated of ML was 16 GE Healthcare Discovery 590HT was used. The radia-
pts/year/Center. IMRT is currently adopted in 95,3% of tion oncologists contoured the volumes of interest
ML cases, according to the facilities of each Center: (CTV) according to the RTOG guidelines. The planning
56% VMAT, 34% IMRT, 10% Tomo-therapy. 92% of target volume (PTV) was generated from the CTV volu-
responders used Image-fusion with pre-chemotherapy me by adding a 3 mm margin in all directions. Accurate
diagnostic imaging to define target volumes. Organ-at- delineation of organ at risk was performed. In these
Risk (OAR) are systematically contoured, and lungs, patients, we used several radiotherapy schedules, accor-
heart, breasts, and esophagus are considered the most ding to volume and site of cancer and considering
relevant. 100% of responders took into account the dose performance status of the patients. Treatment plans
constraints to OAR with 63% of these using ad hoc were evaluated on a dedicated TPS.
“low dose” constraints derived by medical literature Results: 31/38 of these patients ended scheduled
(81%) or single institution experience (19%). In 91% of radiotherapy: 4 patients ended early treatment for car-
treatments, Image-guidance modalities were used to diac condition, 1 for diabetes complications, 2 patients
verify treatment set-up. Respiratory gating was used by died. Median follow up was about 11 months (range 2-
21% of responders. 91% of partecipating Radiation 41). All patients had acute GU toxicity: 20 patients
Oncologists are favourable to the standardization of the (53%) had G1, 13 patients (34%) had G2 and 5 patients
adopted radiation techniques to treat mediastinal (13%) had G3. Late GU toxicity was seen in 8 patients
lymphoma in daily practice and 98% consider useful a (21%) as G1 and in 3 patients (7%) as G2. 21 patients
manuscript on specific dose constraints for lymphoma (55%) had GI toxicity: 15 patients (40%) had G1, 6
radiotherapy. patients (16%) had G2. Late GI toxicity was seen in 5
Conclusions: Radiotherapy plays a significant role patients (13%) as G1. OS was 68% at 1 year, 55% at 2
in the treatment of lymphoma, with high efficacy but years and 38% at 3 year.

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Conclusion: HT is a safe and feasible technique to growth control is attributed to the use of the more sen-
treat unfit patients with bladder cancer. All patients had sitive volume measurements. Transient swelling is a
acute GU toxicity, but it was acceptable for the greatest common phenomenon and should not be mistaken for
part of them. Acute GI toxicity was acceptable too. Late treatment failure. Longer FU is necessary to assess defi-
toxicity, both GU than GI, was never ≥G3. The OS is nitive efficacy and toxicity.
surely influenced by the poor clinical concomitant con-
ditions of the patients too.
PO006

PO005 STEREOTACTIC ABLATIVE RADIOTHERAPY


(SABR) FOR CARDIAC ARRHYTHMIA: A NEW
VOLUME CHANGES AFTER PROTONTHERAPY IN THERAPEUTIC OPTION?
VESTIBULAR SCHWANNOMA: CONTROL RATE, F. Gregucci1, I. Bonaparte1, N. Vitulano2, A. Surgo1,
TOXICITY AND HEARING PRESERVATION R. Mazzola3, A. Di Monaco2, R. Carbonara4,
D. Scartoni, D. Amelio, A. Turkaj, I. Giacomelli, F. Alongi3, T. Langialonga2, M. Grimaldi2,
M. Amichetti A. Fiorentino1
Centro di Protonterapia, APSS, Trento, Italy 1Radiation Oncology Department, General Regional

Hospital F. Miulli, Acquaviva delle Fonti-Bari;


Aims: The purpose of this study was to evaluate the 2Cardiology Department, General Regional Hospital F.
control rate of vestibular schwannomas (VS) after treat- Miulli, Acquaviva delle Fonti, Bari; 3Radiation
ment with protontherapy radiosurgery (SRS) or conven- Oncology Department, IRCCS Sacro Cuore Don
tional protontherapy (SRT) by using a validated volu- Calabria Hospital, Negrar-Verona; 4Radiation
metric measuring tool, toxicity and hearing preserva- Oncology, Policlinico Azienda Universitaria, Bari, Italy
tion.
Methods: Retrospectively, 15 VS patients treated Aim: Despite of therapeutic efforts, cardiovascular
with active beam protontherapy based SRS or SRT diseases are still the first cause of mortality on a global
were analyzed. Baseline and follow-up magnetic reso- scale. In this context, Stereotactic Ablative
nance imaging scans were analyzed with volume mea- Radiaotherapy (SABR) is used in non-oncologic indi-
surements on contrast enhanced T1-weighted (1 mm cations, recently even for cardiac arrhythmias. Thus,
thickness) and three-dimensional constructive interfe- aim of the present review is to analyze preclinical, early
rence in steady-state (3D-CISS) magnetic resonance clinical evidences and future direction of the latter new
imaging. The volume measurements were performed on treatment approach.
axial coupes, using a computer system fitted with spe- Method: A collection of available data regarding
cialized software: Raystation TPS v7.0; volumetric VS SABR and cardiac arrhythmias was made, by Pubmed
analysis was performed in cubic centimeter. Significant research and 2 independent researchers, including pre-
growth was defined as a volume change of 19.7% or clinical and clinical data. A review of ongoing trials was
more. Toxicity was assessed according to CTCAE ver- conducted on ClinicalTrials.gov.
sion 4.03; hearing preservation rates was evaluated Results: Preclinical research conducted in animal
using the Gardner-Robertson grading system as deter- models showed that a safe and efficacy non-invasive
mined by audiogram results. Eleven patients (73%) treatment approach for cardiac arrythmias could be
received 50.4 GyRBE in 28 fractions, 4 patients (26%) represented by SABR with a median time of response
performed protontherapy SRS (12 GyRBE in single around 2-3 months. The technique doesn’t condition the
fraction). results, while the treatment dose plays a crucial role.
Results: At the median follow-up of 24 months The position of arrhythmogenic foci is a relevant
(range 9-53), significant shrinkage was seen in 20%, aspect, considering that in the most studies the atrio-
stable VS in 53%, and significant growth in 27% of the ventricular node would seem more radiosensitive than
patients. In 46% of all patients, transient swelling was the other cardiac electric zone. Clinical data, such as
observed. However, in the significant growth group no published case series, case reports and early prospective
additional treatment was required. No significant studies, have already suggested the feasibility, efficacy
shrinkage was observed in protontherapy SRS group. and safety of SABR (25Gy in one session) for refrac-
Registered acute side effects include G1 (10%) fatigue, tory ventricular arrhythmias. The first prospective sin-
G1 (14%) muffled, G2 (14%) headache, G2 (7%) nau- gle arm study-phase I/II-has shown that through cardiac
sea. There were no G 3 or higher acute toxicities. SABR in single dose of 25Gy using respiratory motion
Registered late side effects include G 1 (7%) and G2 control and image-guided delivery with the support of
(14%) dizziness, G2 (7%) vertigo, G2 (7%) nausea, non-invasive electrophysiology study, a significant
facial nerve deficit (House Brackmann scale G2) (7%). red