Capstone Research Paper Outline

Group7_2019

I. ABSTRACT
II. Introduction
A. Stereotactic body radiation therapy (SBRT) in the treatment of liver cancer or
liver metastases has been shown to be safe and provide excellent outcomes. 1,2
1. Stereotactic body radiation therapy treatment planning goals are to deliver
the prescribed therapeutic radiation dose to the planning target volume
(PTV) and ensure rapid dose fall-off from the PTV to provide needed
organs at risk (OAR) sparing.
2. Dosimetric coverage of PTV is of paramount importance to achieve goals
of both local control (LC) and overall survival (OS).
3. Studies have shown superior outcomes in both LC and OS in patients
treated with liver SBRT when a biologically effective dose (BED 10Gy) of
100 Gy or more is delivered.3,4
4. Inherent risks of increased doses to organs at risk (OAR) are associated
with SBRT and special considerations must be made during treatment
planning.5
5. Challenges in gaining adequate dosimetric coverage to PTV can arise
when it is surrounded by, includes, or abuts tissues of low density such as
lung parenchyma.
B. Differing dose calculation algorithms can result in disparate calculated doses of
both OAR and PTVs that neighbor or include tissues of low densities and can
have the potential to make a clinical impact. 6
1. Although the Analytical Anisotropic Algorithm (AAA) is more widely
 2. Furthermore, AAA has the tendency to overestimate the median and mean
dose to the PTV and gross tumor volume (GTV) respectively, which in
turn has the potential to directly affect clinical outcomes. 7
3. Cakir8 studied dosimetric plan results with 10MV flattening filter free
(FFF) beams using AAA and AXB calculation algorithms in the treatment
of liver lesions and the effect of calculation grid size (CGS), which
showed no significant differences between PTV doses calculated with
AXB 1 mm CGS and AXB with 2.5 mm CGS.
4. This study is limited in that it is not specific to liver PTVs located near the
liver dome which interface with lung tissue.
5. As treatment facilities replace older generation linear accelerators with
modern ones, a greater number of patients will receive stereotactic
radiation therapy treatments with state-of-the-art equipment with enhanced
features such as FFF beams.
C. The utilization of FFF beams, when available to clinicians, has become the
standard for both stereotactic radiosurgery (SRS) and SBRT.
1. The dramatic increased dose rate of FFF beams in comparison to
flattening filter (FF) beams enables a decrease in treatment delivery times
with reduction in OAR and PTV intra-fraction motion.
2. Additionally, patient comfort is enhanced with less time spent on the
treatment table.
3. Flattening filter free beams have several advantages over FF beams
including an increased dose rate factor of 2-4, decreased production of
head scatter, and less lateral transport due to a softer beam spectra. 9
4. Flattening filter free beams and the effects of OAR sparing and PTV
coverage have been studied. Yan et al10 found although PTV coverage
 1. A study performed by Ogata et al11 identified the suitable multi-leaf
collimator (MLC) margins in patients treated with liver SBRT and 10 MV
FFF beams.
2. This study was limited in that an advanced calculation such as AXB was

be at the dome of the liver. Planning target volume coverage challenges

arise in SBRT planning when PTV is associated with tissues of low
densities.12
3. Dosimetric PTV coverage in liver SBRT is critical to achieve positive LC
and OS results.
4. This study intends to find optimal 10 MV FFF beam MLC margins in
SBRT of liver PTVs at the dome of liver utilizing an algorithm with
superior dose modeling capabilities.
III. Methods and Materials
Patients
A. For this single institution retrospective study, 10 patients who treated for primary
liver cancer or liver metastases located at the dome of liver were selected for the
study.
1. Planning target volumes ranged between 7.8 cc and 59.4 cc.
B. Computed Tomography scans were obtained with the patient in supine orientation
with head towards gantry and both arms above head.
1. Computed tomography scans for treatment planning were acquired on a
General Electric LightSpeed 16 slice CT scanner with 2.5 mm slice
thickness during end expiratory breath-hold phase for simulation and
subsequent treatment.
a. RPM (Varian Medical Systems, Palo Alto, CA) system was
 Coralville, IA), and triangle sponge under knees with feet banded as seen
in Figure 1.
Contouring

A. Gross tumor volume was delineated on treatment planning CT scan by the

attending physician in Eclipse (Varian Medical Systems, Palo Alto, CA) version
13.6 treatment planning system.
1. Due to patient simulation and treatment in end expiratory breath-hold
phase, Internal Target Volume (ITV) was not utilized.
2. Planning target volume was then generated by GTV expansion of 1cm in
the superior and inferior directions and 0.5 cm radially.
3. Organs at Risk volumes including the liver, spinal cord, heart, lungs, and
esophagus were outlined by the planning medical dosimetrist.
4. Liver volume was specified as normal liver minus GTV.

Treatment Planning

A. All ten patients selected for this study were planned for 50 Gy to be delivered to
PTV at 10 Gy per fraction for 5 fractions.
1. Treatment plans were created in Eclipse (Varian Medical Systems, Palo
Alto, CA) version 13.6 treatment planning system utilizing a dynamic
conformal arc (DCA) technique consisting of 6 non-coplanar arcs with
each arc travel range between 35 to 60 degrees.
a. Goals were to create a conformal dose distribution surrounding
PTV and to meet OAR dose constraints such as normal liver dose
levels recommended by Pollom et al13 for patients receiving
abdominal SBRT.
2. Flattening filter free 10MV photon beams with dose rate of 2400 monitor
B. Optimized DCA treatment plans using AAA and AXB algorithms were generated
to allow comparison between them in terms of PTV and normal liver metrics.
Subsequently, the AAA plans were recalculated with AXB algorithm with preset
AAA plan MU. The results from the recalculated plans with preset AAA MU
were compared to those of the optimized AXB plans to evaluate differences in
PTV metrics due to the use of independent algorithms. Calculation grid size of
0.25 cm was used for all plans.
1. Dynamic conformal arc treatment plans were generated using AAA
algorithm with various MLC margins surrounding PTV.
a. Multi leaf collimator margins ranged between -3 mm to 5 mm in
1 mm increments.
b. Plan normalization was set such that 95% of PTV received
prescription dose of 50 Gy.
2. Treatment plans with DCA technique were then developed using AXB
algorithm with various MLC margins surrounding PTV.
a. Multi leaf collimator margins ranged between -3mm to 5mm in
1mm increments.
b. Plan normalization was set such that 95% of PTV received
prescription dose of 50 Gy.
3. Optimized AAA plans were then recalculated with AXB algorithm using
preset MU from AAA plans with no plan normalization assigned.
Plan Comparisons

A. Plan result comparisons were made between the optimized AAA and AXB
treatment plans to evaluate differences between them using various quality
indices.
1. Metrics used in analysis were dose received by 99% of PTV volume
 isodose volume (PIVhalf) divided by prescription isodose volume (PIV),
mean liver dose, and volume of liver receiving 20Gy or more (V20Gy).
B. Planning target volume doses were correlated between the optimized AAA plans
and AXB plans recalculated with preset MU from AAA plans.
1. Dose received by 99% of PTV volume (D99), D95, and mean PTV dose
were compared between plans.
C. Optimized AXB plans were then analyzed to identify the optimal MLC margins
using plan quality metrics including PTV D99, mean PTV dose, HI, CI, GI, liver
mean dose and liver V20Gy.

IV. Results
A. The optimized AAA and AXB treatment plans presented similar results in terms
of both PTV and liver doses.
1. Planning target volume D99 for AAA plans was found to be 44.89 Gy,
with PTV D99 44.87 Gy for AXB plans.
2. Mean PTV doses were also found to be comparable between the AAA and
AXB plans, with doses of 62.38 Gy for the former and 62.57 Gy for the
latter.
3. Mean HI, CI, and GI of AAA and AXB plans were found to identical.
a. Calculations of HI, CI, and GI between all MLC margins for
each algorithm studied were found to be 1.4, 1.3, and 3.3
respectively.
4. Liver mean dose was overestimated with the AAA algorithm.
a. Liver D mean for the AAA plans was found to be 5.95 Gy, with
5.89 Gy mean liver dose for AXB plans.
B. Results of plans recalculated with AXB algorithm with AAA plan MU showed
 3. Mean PTV doses for the optimized AAA plans and those recalculated with
AXB algorithm were 62.38 Gy and 62.09 Gy respectively.
C. Optimized AXB treatment plans with various MLC margins results were
analyzed.
1. PTV D99, PTV Dmean, and HI results displayed a linear trend with
increasing MLC margins.
2. The minimum D99 was with -3 mm MLC margins (38.34 Gy) and was
most with 5 mm MLC margins (48.24 Gy).
3. The PTV D mean maximum dose was found with -3 mm margins (84.08
Gy), and minimum PTV D mean was with 5 mm margins (54.16 Gy).
4. The lowest HI value was demonstrated with 5 mm MLC margins (1.15)
with the highest HI value found as a result of -3 MLC margins (2.16).
5. The conformity index results showed optimal values to range between -1
mm margins (1.2), 0 mm margin (1.18) and 1 mm margins (1.2).
6. Gradient indices generally increased with MLC margin.
a. The minimum GI was found to be as a result of -2 mm margins
(2.99) and maximum GI with 5 mm margins (3.83).
7. Optimal liver mean dose values were seen with -1 mm margin (5.47 Gy)
and 0 mm margin (5.41 Gy).
8. The lowest mean liver dose was found with using 0 mm margins (5.41
Gy), with the use of 5 mm margins resulting in the highest mean liver dose
of 6.69 Gy.

V. Discussion
A. Stereotactic body radiotherapy has been shown be safe and effective in the
management of primary liver cancers and liver metastases. 1,2
 2. Advanced calculation algorithms such as AXB have been shown to better
model radiation doses as compared to AAA algorithm, particularly in
regions with high degree of tissue inhomogeneities such as the dome of
liver.7
B. The primary goal of this study was to determine optimal 10 MV FFF beam MLC
margins in SBRT of the dome of the liver.
1. Treatment plans were developed using MLC margins ranging from -3 mm
to 5 mm surrounding PTV utilizing AXB algorithm with analysis of
several plan quality indices.
2. The results displayed optimal MLC margins of 0 mm and -1 mm as seen
across CI, GI, liver mean, and liver V20Gy metrics.
3. The HI increased from 1.36 in plans with 0 mm margin to 1.53 with -1
mm margin, as trend across all plan showed an increase in HI as smaller
MLC margins were used.
4. Mean liver doses were lowest among all MLC margins studied with -1
mm and 0 mm MLC providing liver D mean values of 5.47 Gy and 5.41 Gy
respectively.
5. Planning target volume D99 results were better with MLC margin of 0
mm (44.97 Gy) compared to 43.03 Gy with -1 mm MLC margin.
C. The results of AAA plans recalculated with AXB using AAA MU showed that
AAA algorithm overestimated doses to PTV at the dome of liver.
1. In addition, larger liver doses were reported with results of plans
calculated with AAA algorithm in comparison to results from those
calculated with AXB using AAA MU.
2. Planning target volumes at the dome of the liver included a section of lung
parenchyma, a tissue with a high degree of heterogeneity.
A. In this work on studying the effects of various MLC margins using 10 MV FFF
beams in SBRT of superior liver lesions near the dome, optimal MLC margins
were found to be 0 mm and -1 mm.
1. These findings mirror the results of Ogata et al11 and their identification of
suitable FFF beam MLC margins in liver SBRT.
2. Plans with MLC margins of 0 mm and -1 mm provided optimal normal
liver tissue sparing in addition to having the most favorable CI and GI
values.
3. Dose received by 99% of the PTV was slightly less for -1 mm MLC
margins in comparison to 0 mm MLC margins.
4. Both HI and mean PTV dose values increased linearly as MLC margins
were decreased.
5. A limitation of this study is the wide range of PTV sizes.
6. Further studies are needed to describe the effects of both PTV size and
amount of lung inclusion in PTV on the optimal FFF beam MLC margins
using AXB algorithm.
 References

1. Lee P, Sioshani S. Outcomes of SBRT for HCC in patients with child-pugh B and C
cirrhosis. Int J Radiat Oncol Biol Phys. 2018;102(3);S136.
http://dx.doi.org/10.1016/j.ijrobp.2018.06.334
2. Goodman BD, Mannina EM, Althouse SK, Maluccio MA, Cardenes HR. Long-term
safety and efficacy of stereotactic body radiation therapy for hepatic oligometastasis.
Pract Radiat Oncol. 2016;6(2):86-95. http://dx.doi.org/10.1016/j.prro.2015.10.011.
3. Ohri N, Tome WA, Mendez Romero A, et al. Local control after stereotactic body
radiation therapy for liver tumors. Int J Radiat Oncol Biol Phys. 2018;1. In press.
http://dx.doi.org/10.1016/j.ijrobp.2017.12.288.
4. Mahadevan A, Blanck O, Lanciano R, et al. Stereotactic body radiotherapy (SBRT) for
liver metastasis clinical outcomes from the international multi-institutional RSSearch
patient registry. Radiat Oncol. 2018;13(1):26. http://dx.doi.org/10.1186/s13014-018-
0969-2.
5. Kang KH, Okoye CC, Patel RB, et al. Complications from stereotactic body
radiotherapy for lung cancer. Cancers. 2015;7(2):981-1004.
http://dx.doi.org/10.3390/cancers7020820.
6. Yan C, Combine AG, Bednarz G, et al. Clinical implementation and evaluation of the
Acuros dose calculation algorithm. J Appl Clin Med Phys. 2017;18(5):195-209.
http://dx.doi.org/10.1002/acm2.12149.
7. Padmanaban S, Warren S, Walsh A, Partridge M, Hawkins MA. Comparisons of Acuros
(AXB) and Anisotropic Analytical Algorithm (AAA) for dose calculation in treatment of
esophageal cancer: effects on modelling tumour control probability. Radiat Oncol.
2014;9:286. http://dx.doi.org/10.1186/s13014-014-0286-3.
9. Sharma SD. Unflattened photon beams from the standard flattening filter free
accelerators for radiotherapy: Advantages, limitations and challenges. J Med Phys.
2011;36(3):123-125. http://dx.doi.org/10.4103/0971-6203.83464.
10. Yan Y, Yadav P, Bassetti M, et al. Dosimetric differences in flattened and flattening
filter-free beam treatment plans. J Med Phys. 2016;41(2):92-99.
http://dx.doi.org/10.4103/0971-6203.181636.
11. Ogata T, Nishimura H, Mayahara H, Uehara K, Okayama T. Identification of the
suitable leaf margin for liver stereotactic body radiotherapy with flattening filter-free
beams. Med Dosim. 2017;42(4):268-272.
http://dx.doi.org/10.1016/j.meddos.2017.06.002.
12. Rana S. Clinical dosimetric impact of Acuros XB and analytical anisotropic algorithm
(AAA) on real lung cancer treatment plans: review. Int J Cancer Ther Oncol.
2014;2(1):02019. http://dx.doi.org/10.14319/ijcto.0201.9.
13. Pollom EL, Chin AL, Diehn M, Loo BW, Chang DT. Normal tissue constraints for
abdominal and thoracic stereotactic body radiotherapy. Semin Radiat Oncol.
2017;27(3):197-208. http://dx.doi.org/10.1016/j.semradonc.2017.02.001.
Figures and Tables.

Figure 1. Patient immobilization.