HeadandNeckYao PDF

Multidisciplinary Management
of Head and Neck Cancer I

Min Yao, M.D., Ph.D.
Department of Radiation Oncology
University Hospitals Case Medical Center
Case Western Reserve University
Nothing to disclose
Outline
First Hour:
Laryngeal and Hypopharyngeal Cancer

Nasopharyngeal Cancer
Second Hour:
Oral Cavity Cancer

Oropharyngeal Cancer
The Question:
The best radiotherapy regimen for T2N0 glottic

squamous cell carcinoma is:
A. 1.8 Gy per fraction daily to 70.2 Gy
B. 2.0 Gy per fraction daily to 70 Gy
C. 2.25 Gy per fraction daily to 65.25 Gy
D. 1.2 Gy perfraction twice daily to 79.2 Gy
Treatment of Laryngeal
Squamous Cell Carcinoma
The Larynx
Objectives:
Management of early stage cancer
Management of locally advanced cancer
1. Laryngeal preservation trials with chemoXRT
and patient selection
2. Altered fractionation
3. Radiation with concurrent cetuximab
4. Postoperative radiation
Early Stage of Glottic Cancer

T1A
T1B
Early Stage of Glottic Cancer (T2)
Risk of Lymph Node Metastasis

Glottic Cancer
T1
<2%
T2
<5-8%
T3
15-18%
T4
20-30%
CC Wang. Radiation Therapy for Head and Neck Neoplasms
Radiation Technique for

Early Stage Glottic Cancer
Retrospective study of 315 T1 and 83 T2 patients
Local Control for T1 Disease by Fraction Size
Le. IJROBP 1997
Local Control for T1 Disease

by Overall Treatment Time
Le. IJROBP 1997
Randomized Trial on T1 Glottic Cancer

R
A
N
D
O
M
I
Z
E
Conventional
Fractionation
2 Gy/Fx
Hypofractionation
2.25 Gy/Fx
Tumor < 2/3 of glottis

60 Gy/30 Fx
Tumor > 2/3 of glottis
66 Gy/33 Fx
56.25 Gy/25 Fx
63 Gy/28 Fx
Yamazaki. IJROBP 2006;64:77-82
Local Control Rate Between Arm A and Arm B

2.25 Gy/fx
2 Gy/fx
Yamazaki. IJROBP 2006;64:77-82
Local Control for T2 Disease by Fraction Size
Le. IJROBP 1997
Local Control for T2 Disease

by Overall Treatment Time
Le. IJROBP 1997
2006 ASTRO
RTOG 95-12
HYPERFRACTIONATION FOR
T2 VOCAL CORD CA.
S
T
R
A
T
I
F
Y
Stage
1. T2a
2. T2b
R
A
N
D
O
M
I
Z
E
1. Conventional
Fractionation:
2 Gy/fx/d to
70 Gy/35 fx/7 wks
2. Hyperfractionation:
1.2 Gy/fx BID to
79.2 Gy/66 fxs/6.5 wks
No Difference between the 2 arms
228 patients, with median follow up of 20 months
Radiation Dose Fractions

83 pts (36%) treated BID, 1.1-1.2/fx, total
dose, 74-80 Gy.
147 pts (64%) tx QD. 89 with at least 2 Gy fx.,
57 with 2.06-2.26 Gy/fx, 1 with 1.8 Gy/fx.
Total dose 65 to 75 Gy, median 70 Gy.
Garden et.al. IJROBP 55:2:322-328. 2003
Radiation Treatment Outcomes
P=0.06 N=228
Radiation Treatment Outcomes
Summary for XRT for Early Stage

Glottic Cancer
Radiation to the larynx only. No need

to include lymph node
Higher than 2 Gy daily fraction,

preferable 2.25 Gy/fraction to 63 Gy for
T1 disease and 65.25 Gy for T2 disease.
Limit treatment course < 43 days
Early Stage Supraglottic Cancer

(Clinical Stage T1-2N0-1)
Risk of Lymph Node Metastasis

Glottic Cancer
Supraglottic Cancer
T1
<2%
27 to 40%
T2
<5-8%
27 to 40%
T3
15-18%
55 to 65%
T4
20-30%
55 to 65%
CC Wang. Radiation Therapy for Head and Neck Neoplasms
Early Stage Supraglottic Cancer

(Clinical Stage T1-2N0-1)
Surgical approach
Supraglottic laryngectomy and bilateral
selective neck dissection (level II to IV)
Definitive Radiation alone

Tumor to 70 Gy, 2 Gy/fx, once daily
Whole larynx and bilateral neck to 50-56 Gy
Locally Advanced Laryngeal Cancer

(T3-4, N2-3)

(T3-4, N2-3)
Surgical approach
Total laryngectomy and selective neck
dissection. Post-op XRT +/- chemo.
Laryngeal Preservation with ChemoXRT

Tumor and nodes to 70 Gy, 2 Gy/fx/day
Whole larynx and bilateral neck to 50-56 Gy
VA LARYNGEAL PRESERVATION TRIAL

Surgery
R
A
N
D
O
M
I
Z
E
Radiation Therapy
PR
CR or PR
(3rd Cycle
of Chemo)
Surgery
Radiation
Therapy
CR
Induction
Chemotherapy
(2 Cycles)
< PR
Surgery
Radiation
Therapy
Induction Chemotherapy: Cisplatin and 5-FU

2 yr overall survival of 68%
in both arms
NEJM 1991;324:1685-1690
64% patients (107) in the

induction chemo arm
preserved their larynx.
NEJM 1991;324:1685-1690
RTOG 91-11 Laryngeal Preservation Trial

CR/PR
R
A
N
D
O
M
I
Z
E
CDDP/5FU
CDDP/5FU
No Response
Surgery/XRT
RT plus concurrent cisplatin

RT alone
XRT
RTOG 91-11
Median F/U 3.8 years
Induction
CCRT
RT
2 year Larynx preserved
75%
88%
70%
2 year LR control
61%
78%
56%
8%
9%
16%
55%
54%
56%
2 yr. DM
5-yr. Survival
* Estimated from survival curves
Forastiere et al, NEJM 2003; 349:2091-2098.
RTOG 91-11 Laryngeal Preservation Trial
84%
72%
67%
Median F/U 3.8 years
Forastiere et al, NEJM 2003; 349:2091-2098.
Long Term Update of RTOG 91-11
Forastiere et al, JCO 2013, March
Patient Selection for

Laryngeal Preservation
Patient Factors
Patient preference
Age, co-morbidity
Patient social family support, compliance
Disease Factors
T stage
Tumor volume
Pretreatment laryngeal function

Not Eligible for RTOG 91-11
T4 with tumor extending through the

thyroid cartilage into neck soft tissue
Extending more than 1 cm into base

of the tongue

T4 with tumor extending through the

thyroid cartilage into neck soft tissue
Salvage Laryngectomy at the VA Trial

< T4
28%
T4
56%
p = 0.001

Bulky tumor tumor volume

more than 3.5 cm3 for glottic
cancer and more than 6 cm3 for
supraglottic cancer

Adequate baseline laryngeal function

Tracheotomy
PEG tube dependent
Recurrent aspiration pneumonia
T4A: Thyroid Cartilage Invasion
What to consider
when patients refuse
upfront surgery
or medically inoperable?
Treatment Outcomes for T4 Laryngeal Cancer

Institute
No
Treatment
OS
Larynx Preserved
U Florida1
43
XRT (bid)
37%(5y)
47% (5y)
U Chicago2
32
TFHX
53%(4y)
86% (med 43
mon followup)
U Michigan3 36
ind/conXRT
78%(3y)
67% (med 69
mon followup)
Case4
17
conXRT
64%(3y)
2 pt salvage
laryngectomy
1. IJROBP 1998;40:549; 2. Ann Oncol 2008;19:1650; 3. Laryngoscope 2009;119:1510.

4. 7th International Head and Neck Symposium 2008
Treatment Outcomes for T4 Laryngeal Cancer
About 20 to 25 % patients who did

not need salvage surgery may need
long term tracheostomy or PEG
tube
T4A Laryngeal Cancer
T4A Laryngeal Cancer after ChemoXRT

(T3-4, N2-3)
What to consider
for patients who are not
candidates for chemoXRT and
(refuse) surgery?
Radiation alone with

altered fractionation
Radiation with Cetuximab
RTOG 90-03. PHASE III STUDY OF ALTERED

FRACTIONATION VS. STANDARD FRACTIONATION
S Site
T
R
A
T
I
F
Y
Oral Cavity
Oropharynx
Larynx
Hypopharynx
Stage
N0 vs N+
KPS
90-100 vs
60-80
1. Standard Fractionation
A
N
2. Hyperfractionation
3. Accelerated
Fractionation
(Split-Course)
O
M
I
Z
E
4. Accelerated
Fractionation
(Concomitant Boost)
RTOG 90-03
Standard fractionation
7000 cGy/35 fx
7 weeks
Hyperfractionation
8160 cGy/68 fx
7 weeks (1.2 Gy Bid)
Accelerated fractionation, split course

6720 cGy/42 fx
6 weeks (1.6 Gy Bid)
Accelerated fractionation, concomitant boost

7200 cGy/42 fx
6 weeks
RTOG 90-03 Results

2 yr LRC
2 yr DFS
2 yr OS
Standard
Fractionation
46.0%
31.7%
46.1%
Split-course
Accelerated
47.5%
33.2%
46.2%
Concomitant Boost
54.5%
(p=0.05)
39.3%
(p=0.054)
50.9%
Hyperfractionated
54.4%
(p=0.045)
37.6%
(p=0.067)
46.1%
(p=0.13)
Fu. IJROBP 2000;48:7-16
More than 1400 patients

6 fxs given either daily Monday to Saturday
Or Bid one day in a week (Monday to Friday)
Lancet 2003;362:933-940
DAHANCA 6 & 7
Lancet 2003;362:933-940
DAHANCA 6 & 7
Lancet 2003;362:933-940
Radiation alone with altered fractionation
Accelerated fractionation (Concomitant

Boost)
Six fractions per week (Bid one day per
week, at least 6 hours apart between
fractions)
Radiation plus Cetuximab vs.

Radiation alone
R
A
HNSCC
stage III/IV,
M0
Radiation alone
D
O
M
I
Radiation plus
weekly Cetuximab
Z
E
Bonner et al. NEJM 2006;354:567-578
Kaplan-Meier Estimates of Local Regional Control
Kaplan-Meier Estimates of Overall Survival
Kaplan-Meier Estimates of Overall Survival

5 Year Update
Bonner et al. Lancet Oncol 2010
Radiation technique in locally

advanced laryngeal cancer
Conventional Radiation Techniques

Initial setup
40 Gy, 2
Gy/fx/day
50 Gy, 2
Gy/fx/day
electron

Off Cord
Additional 14 Gy
to 54 Gy

Final Boost
Additional 16-18 Gy to 70-72 Gy
Intensity-Modulated Radiotherapy
In the Treatment of Laryngeal Cancer
IMRT Results for Laryngeal Cancer

Author
No
Locoregional Control Overall Survival
Eisbruch
11
60% (3 y)
NA
Yao
33
85% (2 y)
NA
Lee
20
90% (2 y)
69% (2 y)
Studer
58
65% (3 y)
78% (3 y)
ultimate 82% (3 y)
Daly
19
94% (3 y)
51% (3 y)
Target Delineation For Definitive IMRT

CTV1
GTV + 5 mm (tumor and involved nodes)
CTV2
CTV1 + high risk surrounding tissue (the whole

larynx)
High risk lymphatic areas
CTV3
Intermediate risk lymphatic areas

(lymphatic areas not included in CTV2)
Dose Fractionation in IMRT

PTV1
70 Gy in 33 to 35 fractions
PTV2
60 to 63 Gy in 33 to 35 fractions
PTV3
PTV = CTV + 3-5 mm
T3N1 Laryngeal Cancer
Red PTV1
70 Gy
Purple PTV2 63 Gy
Yellow PTV3 56 Gy
T3N2C Supraglottic cancer
Incorrect IMRT
A patient with T3N0 larynx cancer, received

definitive IMRT
Only the larynx was included in IMRT
Incorrect IMRT
Patient recurred just inferior to the

radiation field
Postoperative Radiation in
Laryngeal Cancer
Postoperative IMRT for Laryngeal Cancer

Stoma > 60 Gy
Treatment of Hypopharyngeal
Anatomy of Hypopharynx
3 parts - the 3 Ps
Pyriform sinus
Posterior pharyngeal wall
Post-cricoid region
Anatomy of Hypopharynx
Pyriform sinus
Pyriform sinus
Pyriform Sinus Cancer
NC
NP
OC
OP
EORTC 24891 LARYNX PRESERVATION

FOR HYPOPHARYNGEAL CA.
R
A
N
D
O
M
I
Z
E
Surgery
Radiation Therapy
Complete
Responders*
Radiation Therapy
Partial or
Non-Responders
Surgery
Induction
Chemotherapy
(3 Cycles)
XRT
Induction Chemotherapy: Cisplatin and 5 FU

J.L. Lefebvre et al, JNCI 88:890-899, 1996

FOR HYPOPHARYNGEAL CA.
S + RT CT+ RT+ S
No. of patients
94
100
5-yr. D-F Survival
27%
25%
5-yr. Survival
35%
30%
Distant Mets.
36%
25%
5-yr. Alive with Larynx
---
17%
J.L. Lefebvre et al, JNCI 88:890-899, 1996

10 year Results
Median F/U: 10.5yrs S + RT CT+ RT+ S
No. of patients
94
100
10-yr. PFS
8.5%
10.5%
10-yr. Survival
13.8%
13.1%
Distant Mets.
36%
25%
10 yr. Alive with functional Larynx 8.7%

J.L. Lefebvre et al, Annals Oncology, 2012
IMRT for Hypopharyngeal Cancer
Include bilateral retropharyngeal

lymph node to skull base
Include level V
Pay attention to the lower edge of the
hypopharynx
IMRT Results for Hypopharyngeal Cancer

Author
No
Locoregional Control
Overall Survival
Eisbruch
12
75% (3 y)
NA
Lee
11
73% (2 y)
53% (2 y)
Studer
65
80% (3 y)
80% (3 y)
ultimate 89% (3 y)
Daly
23
70% (3 y)
45% (3 y)
Liu
27
68.2% (3y)
51.9% (3y)
63% (5y)
34.8% (5y)
NASOPHARYNGEAL
CARCINOMA
INTERGROUP 99 (RTOG 88-17)

Al-Sarraf et al, JCO, 1998
R
A
AJCC
(1992)
III or IV
D
O
M0
RT alone (70 Gy)

Conventional XRT
RT (70 Gy) + CDDP x 3
I
Z
E
CDDP + 5FU x 3

Minimal 5 year follow up for all patients
CT/RT
5 yr progression-free survival
5 yr disease-free survival
5 yr overall survival
58%
RT
29%
(p<0.001)
74%
46%
(p<0.001)
67%
37%
(p<0.001)

Caucasian patients have more WHO
type 1 histology, but Asian patients have
more WHO type 3 histology.
National Cancer Center-Singapore

Joseph Wee, JCO, 2005
AJCC
(1997)
III or IV
M0
WHO II/III
D
O
M
I
N = 221
RT (70 Gy)
Conventional XRT
RT (70 Gy)
CDDP x 3
Z
E
CDDP + 5 FU x 3
National Cancer Center-Singapore

Joseph Wee, JCO, 2005
Median Follow up 37.8 months
CT/RT
RT
2 yr Disease Free Survival
76%
59%
(p=0.027)
2 yr distant metastases-free rate
87%
70%
(p=0.0007)
2 yr overall survival
84%
77%
(p=0.006)
Can chemotherapy add any

benefit beyond
stage III/IV patients?
CCRT vs. RT alone for Stage II NPC

Chen et al. JNCI 2011
R
Chinese
stage
II
D
O
230 Patients
Med Follow-up 5
years
M
I
Z
E
RT (70 Gy)
RT (70 Gy)
Weekly CDDP
(30mg/m2)

Chinese stage II which is equivalent to
AJCC II/III patients
78% received at least 6 cycles of CDDP
and 26% received 7 cycles and 5% 8
cycles
No difference in LRC (93% vs. 91%)

5 year OS:
5 year PFS:
5 year DMFS:
94.5% vs. 85.8%, p=0.007

87.9% vs. 77.8%, p=0.17
94.8% vs. 83.9%, p=0.007
MVA showed the # of chemotherapy cycles

was the only independent factor associated
with better OS, PFS, Distant control
NCCN Guidelines (V2.2011)

T1N0M0
Definitive XRT to
Nasopharynx and
Elective XRT to neck
T1,N1-3, M0
T2-4, Any N
Concurrent ChemoXRT
Followed by adjuvant chemo
Radiotherapy Advances
Intensity Modulated
Radiotherapy
IMRT for NPC:UCSF

Lee et al, IJROBP 2002;53:1:12-21
N = 87
T3/T4:
45%
N+:
79%
Chemotherapy:
III/IV: 74%
85%
4 Year Local Progression-free

97%
N=87
Median F/U=30 months
Lee et al, IJROBP 2002;53:1:12-21
4 Year Distant Metastases-Free

66%
N=87
Lee et al, IJROBP 2002;53:1:12-21
4 year Overall Survival
73%
N=87
Lee et al, IJROBP 2002;53:1:12-21
IMRT(15 studies) vs. Conventional
Local Progression-Free Rate
90-100%
74%-93%
Distant Mets-Free Rate
66%-91%
67%-84%
RTOG 0225 IMRT in NPC

Stage:
I-IVb
Histology:
WHO I-III
R
E
G
I
S
T
E
R
70 Gy to gross
disease
concurrently
59.4 Gy to
microscopic disease
Over 33 days
CT:(T2b and/or + LN)
RTOG PROTOCOL 0225

Lee et al, JCO, 2009
Late complications of Radiation

Xerostomia
Temporal Lobe Necrosis
Oral and dental complications
Hearing loss (more with CCRT)
Pituitary hypofunction
Neural complications
Soft and hard tissue necrosis
Two randomized trials for early-staged NPC

showed IMRT to be superior to
Conventional radiotherapy in terms
Improving salivary function.
Pow EH et al. IJROBP 66:981-991, 2006
Kam MK et al. JCO 25:4873-4879, 2007
IMRT in Nasopharyngeal Cancer
Target Delineation
Dose Prescription
Treatment Planning
Initial stage T1N0 Nasopharyngeal cancer
PET upstaging to T1N1
There appears to be
extension into the
medial aspect of the
left pterygopalatine
fissure and extension
into the left-sided
vidian's nerve into the
skull base.
Target Volumes in NPC

CTV1
GTV-P and GTV-LN plus margins

(5 mm bone and air)
CTV2
High-risk areas with microscopic

disease
CTV3
Lower risk lymphatic regions
Target Volumes in NPC CTV2

CTV2:
CTV2-Primary
CTV2-Node
CTV2-P
CTV1
CTV2-P
Entire nasopharynx,
posterior 4th or 3rd
nasal cavity and
maxillary sinus,
anterior to 2/3
clivus, laterally,
parapharyngeal space.
CTV2-P
CTV2-P
skull base, and
inferior sphenoid
sinus (entire
sphenoid sinus in
T3/4 disease)
CTV2-Node
Bilateral Upper deep
jugular (junctional,
parapharyngeal),
Bilateral Level II, and
level VA, Bilateral
retropharyngeal nodes.
CTV2-Node
And also the lymphatic
region adjacent to
involved nodes
Dose Prescription
PTV 1
70 Gy/33 to 35 fractions
PTV2
60-63 Gy/33 to 35 fractions
PTV3
54-56 Gy/33 to 35 fractions
Radiation Dose Escalation?

Altered Fractionation; Brachytherapy; SRS,
accelerated fractionation in 2D and IMRT era.
None of the trials showed benefit in terms of
tumor control in the setting of chemoradiation.
Late toxicities observed: temporal lobe
necrosis, massive epistaxis, cranial
neuropathies.
IMRT in Nasopharyngeal Cancer
Mean Parotid dose < 26

Gy; 50% of parotid dose
< 30 Gy
70% larynx,
hypopharynx, cervical
esophagus < 45 Gy
Or
Use split-field IMRT if
lower neck is not involved
Max optic nerves 50 Gy
Max BS Dose:
50 Gy
Mean Oral
Cavity 40 Gy
NPC: 2013 and Beyond

Since Intergroup 0099 from 15 years ago,
despite multiple randomized trials, CCRT
followed by adjuvant chemotherapy remains
the standard.
Stage II patients should be offered
chemotherapy.
Patients should be offered IMRT to
maximize target coverage and spare
normal tissues.

Distant failure is main issue with this
disease.
More effective and less toxic
systemic therapy is needed.
Patient selection will be key for all
future studies (EBV DNA).

RTOG Developing Protocol
T>2
or N+
WHO
I-III
R
E
G
I
S
T
E
R
IMRT
(70 Gy)
Plus
CDDP
X3
Low
EBV
High
EBV
R
A
N
D
O
M
I
Z
E
R
A
N
D
O
M
I
Z
E
Observe
CDDP + 5FU
X3
New chemo
Regimen
(Gemcitabine)
Multidisciplinary Management
of Head and Neck Cancer II
Min Yao, M.D., Ph.D.
Department of Radiation Oncology
University Hospitals Case Medical Center
Case Western Reserve University
Treatment of Oral Cavity

Oral Cavity
Treatment Paradigm
Oral Cavity Cancer
Upfront surgical resection

Adjuvant treatment based on
risk factors from pathology
General Indications for Post-operative

Radiation in Head and Neck Cancers
Advanced stage
Multiple lymph nodes involved
Extracapsular extension (ECE)
Positive/close surgical margins
Perineural invasion
Lymphovascular invasion
Oral tongue cancer with deep invasion
General Principles in Post-operative

Radiation in Head and Neck Cancers
Delivered as soon as the wound is healed
Hopefully within 4 to 6 weeks after surgery
Radiation finished within 100 days after
surgery (package time, Rosenthal. Head Neck 2002)
At least 60 Gy
Concurrent chemotherapy in high risk
patients
Risk Adaptive Adjuvant Radiation

Depending on Pathology Features
PORT in Head and Neck Cancer

Phase III Randomized Study to Determine the Optimal Dose
Pathology
adverse Features
ECE
Margin +
>2 N+
T stage
PNI
Oral cavity
primary
R
A Low Risk
N
D
O
M
I
High Risk
Z
E
Dose A
57.6 Gy/32 fx
Dose B
63 Gy/35 fx
Dose C
68.4 Gy/38 fx
Peters, et al. IJROBP 1993;26:3
Local Regional Control by Risk Factors

0-1
2-3
ECE
>4
Peters, et al. IJROBP 1993;26:3
Low Risk
Intermediate Risk
High Risk
Ang et al. IJROBP 2001;51:571-578
Local Regional Control and Survival by Risk Factors
Ang et al. IJROBP 2001;51:571-578
RTOG 9501/EORTC 22931

Surgery
Patients with
high risk
pathology
features
R
A
N
D
O
M
I
Z
E
Arm 1 :
60-66 Gy
Arm 2:
60-66 Gy plus
Cisplatin X3
Results of EORTC Trial 22931 and RTOG 9501

(PORT vs PORT PLUS CHEMO)
EORTC 22931(60 mo)
RTOG 9501(45.9 mo)
End Point
RT
RT+CT
p
value
RT
RT+CT
p
value
5 yr DFS
36%
47%
.04
61%
78%
.04
LR
Control
69%
82%
.007
72%
82%
.01
5 yr OS
40%
53%
.02
57%
63%
.19
Bernier. NEJM 2004; 350:1945
Cooper. NEJM 2004; 350:1937
Overall Survival Results

EORTC 22931
Bernier. NEJM 2004; 350:1945
RTOG 9501
Cooper. NEJM 2004; 350:1937
Combined RTOG/EORTC Analysis
Bernier, Cooper. Head Neck 2005;27:843

Overall Survival for Patients WITH Positive Margin and/or ECE

Overall Survival for Patients WITHOUT Positive Margin and/or ECE
Long Term Follow Up of RTOG 9501

Patients with Positive Margin and/or ECE
Cooper et al. IJROBP 2012
Risk Adaptive PORT depending on Pathology

Risk Features
Management
Low Risk
No Radiation
Intermediate Risk
(neg margin, no ECE)
Radiation alone to 60 Gy
High Risk (pos margin

and/or ECE)
Radiation to 60-66 Gy
with concurrent cisplatin
RTOG 0920 Phase III Intermediate Risk PORT

Eligibility
Perineural invasion;
Lymphovascular invasion;
T1, N1-2 or T2-4a, N0-2,
no extracapsular extension
Close margin (< 5 mm)
T2 oral cavity cancer with
> 5 mm depth of invasion.
R
A
N
D
O
M
I
Z
E
Arm 1 :
60 Gy
Arm 2:
60 Gy plus
Cetuximab X 11
RTOG 1216 Phase II/III High Risk PORT

Eligibility
Stage III or IV HNSCC
Extracapsular extension
< 3 mm surgical margin
R
A
N
D
O
M
I
Z
E
Arm 1 : 60-66 Gy
cisplatin X 6
Arm 2: 60-66 Gy
docetaxel X 6
Arm 2: 60-66 Gy
docetaxel and
Cetuximab
Radiation Technique
for Oral Cavity Cancer
General Principles in Target Delineation in

Postoperative Radiation in HNC
Review pre-operative information including physical
exam and images to understand the extent of the
disease
Read operation note and talk to surgeon to find out
the areas of concern
Read pathology report and talk to pathologist
Deformed registration of pre-operative images to
post-operative simulation CT
If still not sure, ask the surgeon to come to the
planning room when you delineate targets
Target Delineation For Postoperative IMRT

CTV1
Tumor bed (tumor and involved nodes)
CTV2
CTV1 + high risk surrounding tissue

High risk lymphatic areas (hemi-neck)
CTV3

Dose Fractionation in IMRT

Intermediate Risk
High Risk
PTV1
60 Gy (30 fx)
66 Gy (30-33 fx)
PTV2
60 Gy (30 fx)
60 Gy (30-33 fx)
PTV3
54 to 56 Gy (30 fx)
54 to 56 Gy (30 fx)
PTV = CTV + 3-5 mm
Published Series in Postoperative IMRT in Oral Cavity Cancer
Chan et al
Chan et al. Oral Oncology 2013;49:255-260
Failure Patterns after Postoperative IMRT

in Oral Cavity Cancer
Primary tumor bed
Infratemporal fossa/skull base
Pterygoid muscle involvement
Extensive perineural involvement
Contralateral Neck
Area between primary tumor and first echelon
lymphatic region
Yao, et al. IJROBP 2007;67:1332-1341
IMRT Treatment Plan
PET at Recurrence
Yao, et al. IJROBP 2007;67:1332-1341
Anatomy of Inferior Alveolar Nerve and Mental Nerve
Yao, et al. IJROBP 2007;67:1332-1341
Failure Patterns after Postoperative IMRT in Oral Cavity Cancer

CT at Treatment Planning
CT at Recurrence
Yao, et al. IJROBP 2007;67:1332-1341
Failure Patterns after Postoperative IMRT

in Oral Cavity Cancer
Primary tumor bed

High level II/Skull base
Contralateral Neck
1/3 failures were marginal and out-of-field
Contralateral neck failures in patients received
ipsilateral XRT or primary site XRT only
Failures in high level II/skull base in the node
positive neck
Chan et al. Oral Oncology 2013;49:255-260. 180 patients treated at Princess Margaret Hospital
Contralateral Level 1A and 2 Failure
T3N1 oral tongue cancer. Post-op IMRT included only

ipsilateral oral cavity and ipsilateral upper neck
Contralateral Level 2 Failure
T2N1 oral tongue cancer, postoperative radiation

Courtesy of Dr. Nancy Lee
Damast, et al. Head Neck 2012;34:900-906
Ipsilateral Level 3 Failure
T2N1 oral tongue cancer, postoperative radiation

Contralateral Level 2 Failure
T4AN1 oral tongue cancer, postoperative radiation
Submental Failure
Patient with T4AN3 oral tongue cancer with FOM involvement.

Level 1A was not included in the IMRT treatment
Conclusions regarding treatment planning

1. Postoperative IMRT requires careful and comprehensive
target volume delineation, and larger volumes may be needed
than the primary RT setting.
2. Nearly a third of LRFs occurred in marginal or out-of-field
locations, suggesting that more comprehensive radiotherapy
volumes are needed.
3. Bilateral neck irradiation in patients with N2b disease (I say
all oral tongue cancer) and inclusion of high level II (to the
jugular foramen) in the presence of extensive nodal
involvement are recommended.
Chan et al. Oral Oncology 2013;49:255-260.
Oral Tongue Target Summary

Oral tongue: pay attention to the depth of
invasion
Cover the entire tongue
Cover the entire flap
Bilateral neck included
Include level 1b to level IV
Cover high level II in the ipsilateral positive
neck
Oral Tongue Target Summary
Constrictor
T4AN0 Oral Tongue SCC
FOM
Make sure to cover level 1A and the submental

skin well. Placement of Bolus in your planning
Constrictor
SCC of FOM extending into mandible
T4AN2C Buccal Mucosa Cancer,

Recurred at skull base before PORT
Oral Tongue Cancer with Extensive Perineural

Involvement and Skull Base Extension
Oral Tongue Cancer with Extensive Perineural

Involvement and Skull Base Extension
perineural spread
Make sure V3 is covered to the Base of Skull
35 F with recurrent SCC of gingivobuccal sulcus. R chin numbness
Conclusions
Adjuvant treatment based on pathology
features risk adaptive
Careful attention to target delineation
should be done for all cases.
Comprehensive radiation needed
Treatment of Oropharyngeal
Oropharynx Anatomy
Base of the tongue
Tonsils
Anterior and posterior tonsillar pillars
Tonsillar fossa
Soft palate
Posterior and lateral pharyngeal wall
Incidence of Oropharyngeal Cancer

SEER data from 1973 to
2004
Oropharynx (HPVrelated Oral SCC) 17,625
Oral cavity (HPVunrelated Oral SCC)
28,144
Chaturvedi A K et al. JCO 2008;26:612-619

Oropharynx
HPV-related
Oral Cavity
HPV-unrelated
271 OPC collected in SEER

from 1984-2004
Overall incidence of OPSCC
increased by 28%
HPV- positive OPSCC
increased by 225%
HPV- negative OPSCC
decreased by 50%
Incidence Rates for Oropharyngeal Cancer
Human Papillomavirus (HPV)
DNA virus
>100 different sub-types
Infects skin and mucosa
Asymptomatic
Benign growths warts
Oncogenic (cancer
causing) types are mostly
16 and 18
HPV Virus Transforms Normal Cell Into Cancer Cell

Viral DNA
integrates
Nucleus into
normal cell
DNA
Viral DNA
enters
nucleus
Virus
uncoats
viral
proteins E6
and E7
Disables Tumor
Suppressor Proteins
Uncontrolled
cell growth
CA
HPV Biology
E6 protein mediates p53
degradation.
E7 protein binds to
pRb protein releases
E2F => cell cycle
progression to S phase
Presentation
Anatomic Site
Histology
Age
Gender (M:F)
SE Status
Risk Factors
Incidence
Survival
HPV-Positive
HPV-Negative
Tonsil/BOT
Basaloid
Younger
3:1
High
Sexual behavior
Increasing
Improved
All sites
Keratinized
Older
3:1
Low
Tobacco/alcohol
Decreasing
Worse
Presentation
HPV positive tumors tend to present with
smaller primary disease
T1-2 : T3-4 3:2
Most patients (especially HPV +ve) are
node positive
80- 90%
HPV and survival

Trial
Cases
Marker
Survival Rates
First author,
year
RTOG
0129
323
HPV
82% vs. 57% (3year)
Ang, 2010
TROG
02.02
185
p16INK4A
91% vs. 74% (2year)
Rischin, 2010
DAHANC
A 6/7
794
p16INK4A
66% vs. 28% (5year)
Lassen, 2011
TAX 324
111
HPV
82% vs. 35% (5year)
Posner, 2011
Risk Grouping for Overall survival from RTOG 0129

Ang et al NEJM 2010
Oropharyngeal Carcinoma (N=260)

p16-negative (N=73)
p16-positive (N=187)
10 pack-years
(94)
>10 pack-years
(93)
N0-2a
(29)
N2b-3
(64)
10 pack-years
(16)
T2-3
(9)
Low-risk
Intermediate-risk
3-Y OS: 94%
3-Y OS: 67%
(N=123 or 47%)
(N=73 or 28%)
>10 pack-years
(57)
T4
(7)
High-risk
(N=64 or 25%)
3-Y OS: 42%
Risk Classification for Overall survival

by p-16, Smoking, & T-N Category
Ang et al NEJM 2010
Management Strategies in
NCCN grouping
T1 2
N0 - 1
T3 4A
N0 - 1
unresectable
T1 4A
N2 - 3
NCCN guidelines
3 basic recommendations for all groups
Radiation (+/- concurrent chemotherapy)
Surgery (+/- postoperative radiation/
chemoradiation) (except for unresectable
disease)
Induction chemotherapy followed by RT or CRT
(except for early stage disease)
What is the optimal therapy for oropharynx cancer?

No randomized trials (between Surgery vs XRT)
MEDLINE search 1970 2000 51 studies, ~
6400 pts Parsons et al (2002)
Marked similarities in all disease and survival
outcomes
Marked disparity with higher complication
rates in Surgery +/- RT vs RT +/- ND
Comparative functional outcomes poorly
studied
Parsons. Cancer 2002, 94:2967-2980
Trends in treatment for advanced stage

oropharyngeal cancers, 1985 to 2001, National
Cancer Database data, N = 42,688.
2013
Surgery
Changes in Treatment of Advanced

Oropharyngeal Cancer, 1985-2001.
Chen, Amy, et al. Laryngoscope. 117(1):1621, January 2007.
GORTEC French Trial:

Oropharyngeal CA
R
A
Stage III/IV N
D
Oropharynx O
M
I
N=226
Z
E
Arm 1 :
5 FU + Carbo
70 Gy (QD)
Arm 2:
70 Gy RT (QD)
Denis et al. JCO, 2004
GORTEC French Trial:

Oropharyngeal CA
Chemo + RT
5 yr LRC
48%
5 yr DFS
27%
5 yr OS
22%
RT Alone
25%
p=.002
15%
p= 0.01
16%
p=0.05
Denis et al. JCO, 2004
MACH meta-analysis
Set the Stage for concurrent chemoradiation
Individual patient data

1965 1993
63 trials;10,741 pts
Absolute benefit of chemotherapy 4%
Pignon et al. Lancet, 2000
Meta-analysis of locoregional treatment with and

without chemotherapy: absolute effect on survival
Pignon et al. Lancet, 2000
MACH updated (2007)

Through 2000 (including 1965 to 2000); total 87 trials;
16,485 patients
Still 4% survival benefit with chemo adding to radiation;
8% with concurrent chemoradiation
Magnitude of benefit higher with platinum (p < 0.01);
No difference between concurrent poly-chemo and
mono-chemo
Benefit consistent over all tumor locations (Blanchard,
Radiotherapy Oncol 2011)
Pignon et al, Radiotherapy Oncol 2009
MACH updated (2007)
5 year overall survival increased

from 27.4% to 32.7%
Significant
benefits from
studies with
concurrent
chemotherapy
and from studies
using cisplatin
Blanchard. Radiotherapy Oncol 2011
Cisplatin
Traditional cycles - RTOG - 100mg/m2 X 3
cycles (NPC +ve trial, 91-11 larynx preservation,
95-01 and EORTC postop trials, INTERgroup
unresectable trial)
Weekly - ECOG - weekly 20mg/m2 was ve;
now common to see 30 (-40) mg/m2 little HN
data, though cervical (GYN) data.
Daily - Jeremic - 159 pts - randomize
6mg/m2/day CDDP + 70 Gy / > survival and
LRC
Is the more the better?

Is accelerated radiation with
concurrent chemotherapy better
than conventional fractionation
radiation with concurrent
chemotherapy?
GORTEC 99-02 trial
Stage III or IV
of sq cell ca
R
A
N
D
O
M
I
Z
E
QD RT: 70 Gy / 7 weeks
Carbo/5FU (n=279)
Acc RT: 70 Gy / 6 weeks
Carbo/5FU (n=280)
Acc RT : 64.8 Gy/3.5 wks
(n=281)
Median F/U=5.2 years
GORTEC 99-02
Bourhis et al. Lancet Oncology, 2012
RTOG 0129
S
T
R
A
T
I
F
Y
Zubrod PS
R
0 or 1
A
Site : larynx vs N
none
D
Nodal Status : O
M
N0
N1 or N2a-b I
Z
N2c-N3
E
Arm 1: AFX-CB/6 weeks

72 Gy/42 FXS/6 wks
Cisplatin 100 mg/m2
days 1 and 22
Arm 2: 70 Gy in 7 weeks
Cisplatin 100 mg/m2
days 1, 22, 43.
RTOG 0129: Trial Endpoints

Primary Endpoint

Can cetuximab add any benefit to
concurrent chemoradiation?
RTOG 0522
S
T
R
A
T
I
F
Y
Zubrod PS
0 or 1
Site : larynx vs
none
Nodal Status :
N0
N1 or N2a-b
N2c-N3
R
A
N
D
O
M
I
Z
E
Arm 1: AFX-CB or IMRT

plus CDDP 100 mg/m2 days 1
and 22
Plus cetuximab
Arm 2 :AFX-CB or IMRT
plus CDDP 100 mg/m2 days 1
and 22
RTOG 0522
940 patients were enrolled
Median follow-up 2.4 years
2 year progression-free survival: 63% vs. 64%.
p=0.66
2 year overall survival: 83% vs. 80%, p = 0.17
Arm A had higher rates of grade 3-4 mucositis
(45% vs. 35%, P=0.003) and skin reactions
(40% vs. 17%, P<0.0001)
Ang ASCO 2011

The More is NOT the better
Sequential Combined Modality Therapy

A Phase III Study: TAX 324
TPF vs PF Followed by Chemoradiotherapy
T
R
A
N
D
O
M
I
Z
E
Carboplatinum - AUC 1.5

Weekly
F
EUA
P
Surgery
Daily Radiotherapy
TPF: Docetaxel 75D1 + Cisplatin 100D1 + 5-FU 1000 CI- D1-4 Q 3 weeks x3
PF: Cisplatin 100 D1 + 5-FU 1000 CI-D1-5 Q 3 weeks x 3
Posner et al , NEJM 2007
TAX324
TAX 323. NEJM 2007
TAX324
The control arm PF induction chemo not
standard treatment
83% of patients on TPF had grade 3-4
neutropenia and 65% grade 3-4
nonhematologic effects
Only 73% completed treatment per
protocol
The Paradigm Study:

Sequential Therapy vs. Chemoradiotherapy
A Phase III Study of TPF/C-XRT vs P-ACBXRT
T
R
A
N
D
O
M
I
Z
E
T*
ACB
3 Cycles of
NR
Chemotherapy
Surgery
C
F
PR,CR
Daily Radiotherapy
Q 3 Weeks
Surgery
XRT
ACB Radiotherapy
*T + ACB for Non-Responders
Phase III Sequential Trial:

University of Chicago DeCIDE Trial
T
R
A
N
D
O
M
I
Z
E
2 Cycles of
Chemotherapy*
T
H
F
6 Cycles of Every
Other Week
Chemoradiotherapy*
X
T
H
F
6 Cycles of Every Other

Week
Chemoradiotherapy*
X
* Cisplatinum (P); Docetaxel (T); Hydoxyurea (H); 5-Fuorouracil (F); BID Radiotherapy (X)
Randomized Induction Trials

PARADIGM
Terminated due to
slow accrual
Analyzed 145 of
planned 300 pts
3y overall survival
73% induction v 78%
upfront CRT (p=.77)
DeCIDE
280 pts
3y overall survival 75%
induction v 73% upfront
CRT (p=.70)
Lower rates of DF (10% v
19%, p=.025) did not
translate into survival
benefit
ASCO 2012
Conclusion for Induction Chemotherapy

Induction chemotherapy with TPF should NOT
be considered as standard treatment.
It may compromise patients to receive
concurrent chemoXRT due to delay and side
effects.
Use only in patients who may have delay in
definitive concurrent chemoXRT, could not
tolerate radiation, or in clinical trial settings
Radiation Treatment Technique

IMRT
T2 N1 M0 Tonsil Cancer
Primary Tumor
Neck Node
Twenty centers from U.S., Europe and Asia with known H&N
IMRT expertise
Courtesy of Dr. Harari
H&N IMRT
Practice
Heterogeneity
T2 N1 M0 Tonsil Cancer
P. Harari: Radiotherapy & Oncology 2012
Courtesy of Dr. Harari
RTOG Guidelines
RTOG 0022 (T1-2, N0-1)
RTOG 1016 (HPV pos.)
CTV1 GTV + areas

considered to contain potential
microscopic disease; typically
1-2 cm; minimum 5 mm except
if GTV adj to areas known to
be uninvolved
CTV1 GTV + 0.5 1.5 cm
CTV2 High risk subclinical

disease possible local
subclinical infiltration of the
primary site, and first
echelon lymph nodes
CTV2 optional high risk

subclinical disease (first
echelon nodes)
CTV3 remaining neck

nodal levels at risk (nodal
levels not first echelon nodes
and not adjacent to levels
containing grossly involved
nodes)
CTV3 - lymph node groups at

risk
Target Delineation For Definitive IMRT

CTV1
GTV + 5-10 mm (tumor and involved

nodes) minus bone and air
CTV2
CTV2-P CTV1 + high risk adj. tissue

CTV2-N High risk lymphatic areas
CTV3

RTOG Dosing Guidelines

RTOG 0022 (T1-2, N0-1)
RTOG 1016 (HPV positive)
PTV1
66 Gy/30 fx
2.2 Gy/fx
PTV1
70 Gy/35 fx
2.0 Gy/fx
PTV2
60 Gy/30fx
2.0 Gy/fx
PTV2
56 Gy/35 fx
1.6 Gy/fx
PTV3
54 Gy/30fx
1.8 Gy/fx
PTV3
50-52.5 Gy/35 fx
1.43 - 1.5 Gy/fx
Dose Fractionation in IMRT/Chemo

PTV1
70 Gy in 33 to 35 fractions
PTV2
PTV3
PTV = CTV + 3-5 mm
Base of Tongue Target Delineation

CTV 1
(Red)
Base of Tongue Target Delineation

CTV2
(Blue)
CTV 3
(Yellow)
Base of Tongue Isodoses
Tonsil Target Delineation

CTV 1
(Red)
Courtesy of Dr. Garden
Tonsil Target Delineation

CTV 1
(Red)
CTV2
(Blue)
CTV 3
(Yellow)
Tonsil planning 3-D view

CTV 1
(Red)
CTV2
(Blue)
CTV 3
(Yellow)
Tonsil isodoses
RTOG Dosing Guidelines

95% of the high dose PTV covered with
prescription
No more than 20% to receive >110% dose
No more than 1% to receive < 93%
No more than 1% (or 1 cc) outside PTV
should receive >110%
IMRT for Oropharynx

First Author, year
Patient
number
Median
follow up
(months)
Disease control
Feng, 2005
94
36
94% (LRC, crude)
Studer, 2007
105
88% (LC, 2y)
Mendenhall, 2010
130
42
84% (LRC, 5y)
Daly, 2010
107
29
92% (LRC, 3y)
Setton, 2010
442
37
95% (LC, 3y)
Sher, 2012
163
36
86% (LRC, 3y)
Garden, 2012
776
54
90% (LRC, 5y)
Clavel, 2012
100
42
95% (LRC, 3y)
Ipsilateral Radiation in
Lateralized Tonsil Cancer
T1-T2, N0-N1 tumor
Less than 1.0 cm extension to soft palate
No base of tongue involvement
ACR Appropriateness Criteria. Head Neck 2012;34:613-616
Stage T2N0 Tonsil Cancer
Ipsilateral Radiation in Tonsil Cancer
Ipsilateral tonsil radiation

First author,
year
Patient
number
% N0-1
% T1-2
Contralateral
neck failure
Jackson, 1999
178
87%
65%
3% (N0-1)
Kagei, 2000
32
84%
56%
0%
O Sullivan, 2001
228
83%
84%
3%
Rusthoven, 2009
20
20%
90%
0%
56%
100%
2%
Chronowski, 2012 102
26 patients treated with IMRT versus 27 with conventional XRT.
QOL for IMRT in Oropharynheal Cancer

Main HNCI domain scores at 12 months after treatment
Yao. IJROBP 2007;69:1354-1360

Types of diet at 12 months
Yao. IJROBP 2007;69:1354-1360

Mean eating scores across the first year
Yao. IJROBP 2007;69:1354-1360
Nutting. Lancet Oncol 2011;12:127-36

Mean EORTC HN35 dry mouth score
Nutting. Lancet Oncol 2011;12:127-36
Future Prospective
Management of HPV-related
De-escalation Regimens
RTOG 1016 - Cetuximab-RT vs ChemoRT
Eligibility
Oropharynx
P16 pos
T1-2, N2a-3
T3-4 any N
N=700
3.8 yrs to enroll
~8 yr to analysis
S
T
R
A
T
I
F
Y
T-stage
T 1,2
T 3,4
N-stage
N0-2A
N2B-C
Smoking
<10 PY
>10 PY
Zubrod
1
2
R
A
N
D
O
M
I
Z
E
IMRT 70 Gy in 6 wks
cisplatin x 2
IMRT 70 Gy in 6 wks
cetuximab for 8 wks
IMRT 6 fractions per week
ECOG 1308: HPV-specific Trial
Chemotherapy to Select Patients for Lower Dose Radiation
INDUCTION
ELIGIBILITY
Stage
III,IVA,B
Resectable
HPV +
Oropharynx
N=83
CR
(3 cycles)
CONCURRENT
IMRT 54Gy/27 fxs
Cetuximab 250mg/m2 qwk
Weekly
Paclitaxel
+
CONCURRENT
Cetuximab
IMRT 69.3Gy/33fxs
<CR
Cetuximab 250mg/m2 qwk
Cetuximab loading dose = 400mg/m2 on Day1 of Cycle1 with Induction
Advancement in Surgery
Historical surgeries for OPC were
open resections
Advent of minimally invasive transoral
techniques
TLM transoral laser microsurgery
TORS transoral robotic surgery
Minimally Invasive Surgery

First
author,
year
Patient Surgery
number
T1 2 (%) /
N2c(%)
XRT / ChemoXRT
LRC
Moore,
2012
66
TORS
+ND
90% /12%
21% / 42%
97%
LC/94% RC
Genden,
2009
20
TORS
+ND
100% / 0%
35% / 15%
ND
Weinstein,
2012
30
TORS
+ND
83% / 0%
0%/ 0%
97% LC
Weinstein,
2010
47
TORS
+ND
76% / 4%
28% / 57%
98%
LC/96% RC
White,
2010
89
TORS +/ND
80% / 13%
63% / ND
89%
Haughey,
2011
204
TLM +ND 66% / 8%
54% / 25%
93%
ECOG 3311 P16+ Trial Low Risk OPSCC:

Personalized Adjuvant Therapy Based on Pathologic
Staging of Surgically Excised HPV+ Oropharynx Cancer
Assess
Eligibility:
HPV (p16)+
SCC
oropharynx
Stage III-IV:
cT1-3, N1-2b
(no T1N1)
Baseline
Functional/
QOL
Assessment
LOW RISK:
T1-T2N0-N1
negative margins
Observation
Radiation Therapy
IMRT 50Gy/25 Fx
Transoral Resection
(any approach)
with neck dissection
HIGH RISK:
Positive Margins
> 1 mm ECS or
4 metastatic LN
R
A
N
D
O
M
I
Z
E
INTERMEDIATE:
Evaluate for 2-yr PFS
Clear margins
Local-Regional Recurrence,
1 mm ECS
23 metastatic LN Functional Outcomes/QOL
PNI
LVI
Radiation Therapy
IMRT 60 Gy/30 Fx
Radiation Therapy
IMRT 66 Gy/33 Fx +
CDDP 40 mg/m2 wkly
RTOG Randomized Phase II High Risk OPSCC:

Risk Based Therapy for HPV negative Oropharynx Cancer
Assess
Eligibility:
HPV (p16)
negative SCC
oropharynx
Stage III-IV:
cT1-3, N0-2b
Baseline
Functional/
QOL
Assessment
R
A
N
D
O
M
I
Z
E
IMRT 70 Gy
+/- chemotherapy
Transoral Resection and

Neck dissection
Risk-based PORT
+/- chemotherapy
Conclusions
Increased incidence of oropharyngeal cancer due to
HPV
Concurrent chemoXRT is the standard for locally
advanced oropharyngeal cancer .
IMRT offers better QOL in oropharyngeal cancer.
Dose de-escalation under investigation in HPVrelated oropharyngeal cancer.
Role of minimal invasive surgery needs to be defined.
The Question:
The best radiotherapy regimen for T2N0 glottic

squamous cell carcinoma is:
A. 1.8 Gy per fraction daily to 70.2 Gy
B. 2.0 Gy per fraction daily to 70 Gy
C. 2.25 Gy per fraction daily to 65.25 Gy
D. 1.2 Gy perfraction twice daily to 79.2 Gy

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Multidisciplinary Management

of Head and Neck Cancer I

Laryngeal and Hypopharyngeal Cancer

Oral Cavity Cancer

The best radiotherapy regimen for T2N0 glottic

Early Stage of Glottic Cancer

Early Stage of Glottic Cancer (T2)

Risk of Lymph Node Metastasis

Radiation Technique for

Retrospective study of 315 T1 and 83 T2 patients

Local Control for T1 Disease by Fraction Size

Le. IJROBP 1997

Local Control for T1 Disease

Le. IJROBP 1997

Randomized Trial on T1 Glottic Cancer

Tumor < 2/3 of glottis

Yamazaki. IJROBP 2006;64:77-82

Local Control Rate Between Arm A and Arm B

Yamazaki. IJROBP 2006;64:77-82

Local Control for T2 Disease by Fraction Size

Le. IJROBP 1997

Local Control for T2 Disease

Le. IJROBP 1997

228 patients, with median follow up of 20 months

Radiation Dose Fractions

Garden et.al. IJROBP 55:2:322-328. 2003

Radiation Treatment Outcomes

Garden et.al. IJROBP 55:2:322-328. 2003

Radiation Treatment Outcomes

Garden et.al. IJROBP 55:2:322-328. 2003

Summary for XRT for Early Stage

Radiation to the larynx only. No need

Higher than 2 Gy daily fraction,

Limit treatment course < 43 days

Early Stage Supraglottic Cancer

Risk of Lymph Node Metastasis

CC Wang. Radiation Therapy for Head and Neck Neoplasms

Early Stage Supraglottic Cancer

Definitive Radiation alone

Locally Advanced Laryngeal Cancer

Locally Advanced Laryngeal Cancer

Laryngeal Preservation with ChemoXRT

VA LARYNGEAL PRESERVATION TRIAL

Induction Chemotherapy: Cisplatin and 5-FU

VA LARYNGEAL PRESERVATION TRIAL

VA LARYNGEAL PRESERVATION TRIAL

64% patients (107) in the

RTOG 91-11 Laryngeal Preservation Trial

RT plus concurrent cisplatin

2 year Larynx preserved

Forastiere et al, NEJM 2003; 349:2091-2098.

RTOG 91-11 Laryngeal Preservation Trial

Median F/U 3.8 years

Forastiere et al, NEJM 2003; 349:2091-2098.

Long Term Update of RTOG 91-11

Forastiere et al, JCO 2013, March

Long Term Update of RTOG 91-11

Forastiere et al, JCO 2013, March

Long Term Update of RTOG 91-11

Forastiere et al, JCO 2013, March

Patient Selection for

Patient Selection for

T4 with tumor extending through the