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CCRT in Oropharynx and Oral Cavity Cancer
Dr. A.K. AnandDirector, Deptt of Radiation Oncology,Max Cancer Centre, Max Hospital,
New Delhi - 110085
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HEAD AND NECK CANCERS HEAD AND NECK CANCERS HEAD AND NECK CANCERS HEAD AND NECK CANCERS –––– INDIAN INDIAN INDIAN INDIAN
EXPERIENCEEXPERIENCEEXPERIENCEEXPERIENCE
� In the year 2005 at RGCI, Delhi – 1248/6728 patients
(18.54%) had Head and Neck Cancer.
� Males – 1158/3736 (30.9%)� Males – 1158/3736 (30.9%)
Females- 90/2992 (3.01%) M:F - 10:1
� National cancer registry data (New Delhi) shows Head and
Neck constitutes 15.4% of all cancers.
� MAX HOSPITAL,NEW DELHI 2009—HNC 285/1872 (15.3%)
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Treatment aims in locally advanced SCCHN
• Overall survival
• Concurrent RT + CT Vs Neo- Adj CT and RT
• Organ-function preservation
• Symptom control
• Quality of life
– Minimal long-term toxicity
– Tolerability
– Patient satisfaction
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� Radiation with concurrent chemotherapy is
considered to be the standard of care for locally
advanced and unresectable Head and Neck
Cancers.
LOCALLY ADVANCED HEAD AND NECK
CANCERS
Cancers.
� Surgery + Radiation therapy is reserved for certain
sites only
� RT + CT has an important advantage of conservation
of organ related to speech and swallowing.
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Improved Survival in H & N Cancers
�Patients treated between 1988-97 and 1998-2004 (SEER Data)�Patients treated between 1988-97 and 1998-2004 (SEER Data)
�Patients treated after 1998 had 7.6% & 6.1% absolute improvement in overall and cause specific survival
� The absolute OS benefit observed is likely related to improvement in efficacy of treatment with Concurrent RT+CT
�Proportion of patients treated with RT has also increased over time attributable to improvements in Larynx preservation
IJROBP Vol. 72 (2) pp 343-50, 2008
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Improved Survival in H & N Cancers
IJROBP Vol. 72 (2) pp 343-50, 2008
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Locally advanced Head & Neck Cancers
Concurrent RT + CT Vs Radiation Alone
Neo Adjuvant Chemo Vs Concurrent Chemo-Radiation
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Sequential Therapy of Locally advanced
Larynx and Hypopharyngeal Cancers
TAX324
TPF (n=255)
Induction Chemotherapy
(operable or inoperable )
(3 cycles ) PF (n = 246)
Responders RT+CT (66-70 Gy
with weekly CARB
Annals of Oncology 20:921-27,2009
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EORTC 24971 / TAX 323
• Induction TPF
Or Responders Radiation 66-70 Gy66-70 Gy
• PF 3-4 Cycles
NEJM 357, 1695 -1704, 2007
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Chemo-RT Vs Radiation alone
Bernier J et al. Wiley Inter Science: 2005; 843-850
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Chemo-RT Vs Radiation Alone
Bernier J et al. Wiley Inter Science: 2005; 843-850
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Hazard ratio with loco-regional treatment plus chem otherapy versus loco-regional treatment alone by timing of chemothe rapy.
MACH-NC 2009 DATA
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Hazard ratio of death with loco-regional treatment plus concomitant chemotherapy versus loco-regional treatment alone by type of chemothera py. The test of HRs for poly and mono-chemotherapy . MACH-NC UPDATE-2009(Radioth &Oncol9 2(2009)4-14
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MACH-NC ANALYSIS 2009
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CONCURRENT Vs INDUCTIONRT+CT in LAHNC
TPF – RT+CT (TAX324)
EORTC
24971/TAX323
RT+Erb
(Bonner et al)
PFS 2 Yrs (%) 48 % 25 % 50 %PFS 2 Yrs (%) 48 % 25 % 50 %
3 Yrs (%) 43 % 17 % 48 %
OS 2Yrs (%) 64 % 43 % 65 %
3 Yrs (%) 57 % 37 % 55 %
LRF (%) 32 %
DM 6 % 12.9 %
DM+LRF 1 % 2 %
Second PRT 2 %
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Comparison of overall survival advantage of different combinations (MACH-NC meta-analyses,
Bonner study)
Hazard ratio Hazard ratio (95% CI)(95% CI)
CT or CT or ErbituxErbituxeffect effect
(p(p--value)value)
Absolute benefitAbsolute benefit
At At 2 2 yearsyearsaa
At At 5 5 yearsyearsaa
Adjuvant CT+RTAdjuvant CT+RT11 0.980.98(0.85(0.85––1.19)1.19)
0.740.74 1%1% 1%1%
NeoadjuvantNeoadjuvantCT +RTCT +RT11 0.95 0.95 0.100.10 2%2% 2%2%NeoadjuvantNeoadjuvantCT +RTCT +RT11 0.95 0.95 (0.88(0.88––1.01)1.01)
0.100.10 2%2% 2%2%
Concomitant CT + RTConcomitant CT + RT11 0.81 0.81 (0.76(0.76––0.88)0.88)
<0.0001<0.0001 7%7% 8%8%
ERBITUX + RTERBITUX + RT22 0.73 0.73 (0.56(0.56––0.95)0.95)
0.020.02 7%7% 10%10%
aAssuming survival rates of 50% at 2 years and 32% at 5 years in control groups
Pignon JP, et al. Lancet 2000;355:949–955
Bonner J.A, et al. as presented ASTRO 2008
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Concurrent RT + CT in Oral Cancers
• Usually Post-operative.
• Indicated in “High Risk” patients.
– R1 – Resection (margin positive).
– Nodal Metastasis with Extra Capsular Extension (ECE ).
– pT3 or pT4 primary.
– N2 or N3 nodal disease
– Nodal disease in levels IV or V
– Perineural invasion
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Bernier J et al. NEJM 2004; 1945-1952
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Bernier J et al. NEJM 2004; 1945-1952
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Bernier J et al. NEJM 2004; 1945-1952
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EORTC 24971 /Tax 323
Febrile Neutropenia 5.2 % TPF
Neutropenia 76.9 %
Anemia 9.2 %
Thrombocytopenia 5.2 %Thrombocytopenia 5.2 %
Infection 12 %
Deaths 2.3 % (5.5 % PF)
Stomatitis 23.7 %
esophageal dysphagia 13.9 %
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Hitt R et al. J supportive Oncol 2005; 23 (suppl 16): Abstract 5578
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Swallowing Toxicity after Chemoradiation for Head & Neck Cancer
Chemoradiation Trials -Therapeutic and Functional Outcomes
Trial Radiation Chemotherapy Swallowing Toxicity
RTOG 99 -14 94 72 Gy over 6 weeks; Cisplatin FT rate ,82.9%, 1 year single arm;phase II 40.9%;2year,21.8%
Starr 95 69.9Gy over 38 sdays Fluoroucil +carboplatin 2 Year FT rates 51% v 25% p= .02
RTOG 91-116 70Gy over 7 weeks Cisplatin 14%,16% of both of RTOG 91-116 70Gy over 7 weeks Cisplatin 14%,16% of both of groups had
“difficult swallowing”
Intergroup 0126 70Gy over 7 weeks Cisplatin 52%v 40%;P=0.08 acute FT ratios
Abitol 74.4Gy over 16 weeks Cisplatin Flurocil+mitomycin-C 8% FT dependency chronic;7%
Erbuch 70Gy ,single arm phase 1 Gemcitabine Chronic FT rate 28%
GORTEC 94.0196 70Gy over 7 weeks Cisplatin +Fluorocil FT rate overall,37% v 15% ,
p=.02;15%
Kies 97 75 Gy over 9 weeks Pacilitaxel; Carboplatin; Fluoroucil , 1 year FT rates 20%:single arm phase 1
FT- Feeding Tube
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PEG-Insertion
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CRT is associated with more frequent and longer treatment interruptions than RT
15
20
25
Pat
ient
s (%
)
23%
18%
14%
17%
Calais C, et al.
Huguenin P, et al.
6.2
days
8.9
days
6
8
10
No.
of d
ays
6.2
days
8.9
days
Calais C, et al.
0
5
10
15
Unplannedtreatment
interruptions
Treatmentinterruptions ≥3 days
Pat
ient
s (%
)
14%
3 da
ys 4 da
ys
6.2
days
RT CRT
Calais G, et al. J Natl Cancer Inst 1999;91:2081–2086; Huguenin P, et al. J Clin Oncol 2004;22:4665–4673
0
2
4
Median Mean
Duration of treatment break
No.
of d
ays
3 da
ys 4 da
ys
6.2
days
Huguenin P, et al.
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CRT: compromised postoperative adherence to CT
1 88%
Trea
tmen
t cyc
le
►►Number of patients receiving Number of patients receiving cisplatincisplatin on time on time and without delay decreases over timeand without delay decreases over time
0 20 40 60 80 100
3
2
Bernier J, et al. N Engl J Med 2004;350:1945–1952
66%
Patient compliance with CT (%)
Trea
tmen
t cyc
le
49%
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CHRONIC TOXICITY
1. Xerostomia (dry mouth) : >66%
2. Difficulty eating / swallowing : 35%-68%
3. Sticky salvia : 33%
4. Decreased sense of taste : 25-50%
TOXICITY OF CONVENTIONAL RADIATION
4. Decreased sense of taste : 25-50%
5. Dental problems : 33%
6. Pain : 15-30%
7. Appearance : 20-25%
8. Trismus
9. Silent Aspiration & Asp. Pneumonitis
List MA et al Semin. Radiat. Oncol Vol:14, No-2: 2004
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RT + Erbitux in locally advanced SCCHN
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Patterns of care in locally advanced SCCHN
Treatment patterns in Europe*(incl. RT only, excluding surgery)
17% 17% 19%
17%
20% 21% 19%12%
RT only
CT only
CRT
*Europe: France, Germany, Italy, SpainBudach et al. ESMO 2010, Abstract No.1033P
2% 3%6%
0,4%3%
3%
18%
24%
55%43%
37%
36%
6%
15%
2006 (927 pts)
2007(923 pts)
2008 (1239 pts)
2009 (1220 pts)
CRT
Erbitux+RT
Erbitux only
Erbitux+CT+RTErbitux+CT
Erbitux (all combinations)
18% 26%36%
9%
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RT + Erbitux (n=211)
Erbitux initial dose (400 mg/m 2)Erbitux (250 mg/m 2) + RT (wks 2–8)
Stage III and IV non-metastatic
SCCHN R
Erbitux in locally advanced SCCHN: Bonner Phase III study
N=424
RT (n=213)
Bonner et al. NEJM 2006
Primary endpoint : duration of locoregional control
Secondary endpoints : OS, PFS, RR, QoL, and safety
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Erbitux in locally advanced SCCHN: Significant benefit in locoregional control
Loco
regi
onal
con
trol
(%
)
100
80
6024.4 months
HR=0.68 [95% CI: 0.52–0.89] p=0.005
3-year control rate
47%
RT + ErbituxRT
Months
Loco
regi
onal
con
trol
(%
)
60
40
20
00 10 20 30 40 50 60
14.9months
24.4 months 47%
34%
Bonner et al. NEJM 2006
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Erbitux in locally advanced SCCHN:5-year survival update
HR=0.73 [95% CI: 0.56–0.95]p=0.018
100
90
80
70
60
Ove
rall
surv
ival
(%
)
49.0 months 46%
5-year survival rate
RT + ErbituxRT
Bonner et al. Lancet Oncol 2010
60
50
40
30
20
10
00 10 20 30 40 50 60 70
Ove
rall
surv
ival
(%
)
29.3months
36%
Months
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RT + Erbitux: Relevant grade ≥≥≥≥3 adverse events
Mucositis/stomatitis
Dysphagia
Radiation dermatitis
Xerostomia
RT (n=212)RT + Erbitux (n=208)
p<0.001
p=0.01
Patients (%)
*Listed for its relationship to Erbitux
Median duration of any mucositis or dysphagia in th e overall population: similar in both treatment groups (12–13 weeks)
0 10 20 30 40 50 60
Fatigue/malaise
Acne-like rash
Infusion reactions*
Bonner et al. NEJM 2006
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Glo
bal h
ealth
sta
tus/
QoL
sco
re 100
80
RTErbitux + RT
Adding Erbitux to RT increases survival without compromising QoL
Curran et al. JCO 2007QoL: post-baseline scores for the EORTC QLQ-C30
Glo
bal h
ealth
sta
tus/
QoL
sco
re
60
40
20
0
Visit
Baseline Week 4 Month 4 Month 8 Month 12
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Efficacy: Survival benefit
Rx regimens HR Absolute Benefit
(95% CI) 5-Year
RT + concurrent CT 1
vs RT alone0.81
(0.76–0.88)8%
Cisplatin + 5-FU 0.77(0.69–0.85)
10%
Cisplatin alone 0.73(0.56–0.95)
11%
RT + Erbitux vs RT alone 2,3 0.73(0.56–0.95)
9%
TPF (vs PF) ���� RT4 0.73(0.56–0.94)
TPF (vs PF) ���� RT + Carboplatin 5 0.70(0.54–0.90)
1Pignon et al. Lancet 2000; 2Bonner et al. NEJM 2006; 3Bonner et al. Lancet Oncol 2010; 4Vermorken et al. NEJM 2007; 5Posner et al. NEJM 2007
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Adding ERBITUX to RT provides similar efficacy to concomitant CRT
The immediate larynx preservation (LP) rate after T PF followed by ERBITUX + RT is similar to TPF followed by cisplati n + RT
80
100 9298
LP r
ate
3 m
onth
s af
ter
trea
tmen
t (%
)
0
20
40
60
80
CRT ERBITUX + RT
LP r
ate
3 m
onth
s af
ter
trea
tmen
t (%
)
Lefebvre J et al. J Clin Oncol 2009;27(Suppl. 15):Abstract 6010
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Combining ERBITUX with RT ensures more patients will be treated as planned
More patients were able to complete their ERBITUX + RT course compared with patients receiving CRT
60
80 71
Pat
ient
s co
mpl
etin
g R
T
afte
r in
duct
ion
ther
apy
(%)
0
20
40
60
CRT ERBITUX + RT
43
Pat
ient
s co
mpl
etin
g R
T
afte
r in
duct
ion
ther
apy
(%)
Lefebvre J et al. J Clin Oncol 2009;27(Suppl. 15):Abstract 6010
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� Several critical organs in close proximity to the
tumor
� Organ motion practically absent
Why IMRT In Head & Neck Cancers ?
� Patient set up uncertainties manageable
� Conventional radiation is associated with several
side effects which can be permanent
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ADVANTAGES OVER CONVENTIONAL RADIATION
IMPROVED TUMOUR DOSE
� Dose constraints on tumor reduced due to sharp
IMRT IN HEAD & NECK CANCERS
� Dose constraints on tumor reduced due to sharp
fall of dose
� Higher dose of radiation can be delivered to the
tumor due to better protection of critical organs
like spinal cord, eye, optic nerve etc.
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REDUCTION OF NORMAL TISSUES TOXICITY
TISSUES WITH TANGIBLE GAINS
1. Sparing of parotids glands avoiding xerostomia
and dental caries
2. Mandible
IMRT IN HEAD & NECK CANCERS
2. Mandible
3. Pharyngeal mucosa & musculature
4. Inner & middle ear
5. Temporal mandibular joints
6. Temporal brain lobes
7. Optic pathways
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Concurrent RT + CT in Oral Cancers
• Critical Issues in Radiation Planning:
– Identify Preoperative Tumor Extension with clinical and
Radiological correlation. Radiological correlation.
– Identify high risk areas – Bone Invasion, location o f
positive nodes and ECE for SIB if feasible.
– Trace Cranial Nerves in Adenoid Cystic Carcinoma or
Extensive PNI upto base of skull.
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Contralateral Neck – Level II classical –
where Post belly of diagastric muscle is crossed by IJV
(* Eisbruch et al IJROBP 2004; 59(1): 28-42), (* Dawson et al )
Cranial extent of high
Diagastric Ms crossing IJV (Cranial extent of low risk
neck)
Cranial extent of high risk neck
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Carotid artery
Styloid process
Superior most axial CT
image at which level II
nodal target delineated in
side of neck Ipsilateral to
primary tumor in post -
styloid region.
HIGH RISK NECK
Tip of Mastoid
Internal jugular veins
Carotid artery
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Diagastric Ms crossing
Superior most axial CT image
at which level II nodal target
delineated in side of neck
contralateral to primary
tumor.
LOW RISK NECK
Diagastric Ms crossing IJV (Cranial extent of
low risk neck)
IJV
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Knowledge of Radiological Anatomy needs to be enhanced
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• Buccal Mucosa – Inclusion of ITF (Infratemporal fossa) in upper alveolus RMT lesions. lesions.
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Pt. name – S.J., Age – 54/F, Reg. No. – SKDD. 392184
Ca Right Buccal Mucosa (recurrent), T4N0M0-Infratemporal fossa inclusion
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Pt. name – A.P., Age – 54/M, Reg. No. – SKDD. 335034
Ca upper alveolus with Extensive PNI & Cranial Ns involv.
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Pt. name – A.P., Age – 54/M, Reg. No. – SKDD. 335034
Ca upper alveolus with Extensive PNI & Cranial Nerves involv –Target Delineation
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CA TONSIL TREATED WITH IMRT –PAROTID SPARING
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Ca Oropharynx – FDG avid tumor at Primary site and
Metastatic Lymphnode. Target volume with CT-PET fusion
ill defined Primary Tumor definition
Well defined
Primary
Tumor
definition
CECT CT-PET Fusion
Well defined
Lymphnode
showing
metastasis
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Rapid Arc™ Objectives
• Single arc IMRT
• IMRT quality
– Uniform target coverage
– Improved normal tissue – Improved normal tissue sparing
• Treat in 2 minutes or less
– Highly efficient
– Low peripheral dose
• Simple planning and delivery
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Rapid Arc - IMRT Quality
1685 MU496 MUSRapidArc
Single arc IMRT Conventional
7-field IMRT
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RESULTS: Conventional Radiation best results with Conventional
Radiation reported in RTOG 9003 STUDY – On Locally Advanced
Head & Neck Cancers 2 Years Loco Regional Control - 54.5%
IMRT
Patient No. Patient No. Sites Sites Median FollowMedian Follow--up up
(Months) (Months)
LocalLocal--Regional Regional
Control Control
IMRT IN HEAD AND NECK CANCERS
(Months) (Months) Control Control
Lee et al
Chao et al
Yau et al
Dawson et al
Anand et al
67
126
60
58
62
Nasopharynx
Head & Neck
Head & Neck
Head & Neck
Head & Neck
31
26
17.5
27
19
97% (4yr)
85% (2yr)
87% (1yr)
79% (2yr)
77% (2yr)
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IMRT +/- Chemotherapy Experience (n=62)
Kaplan Meier estimate of Loco-regional control (A) and Overall survival (B)
Anand et.al, British Journal of Radiology (2008) 81, 865-871
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Anand et.al, British Journal of Radiology (2008) 81, 865-871
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Disease Free Survival1.1
1.0
.9
.8
.7
.6
.5
.4
Overall Survival1.1
1.0
.9
.8
.7
.6
.5
.4
Overall Survival of RT + Erb + Cisplat.
Month
3024181260
Cum
Sur
viva
l
.3
.2
.1
0.0
Survival Function
Censored
Months
3024181260
Cum
Sur
viva
l
.3
.2
.1
0.0
Survival Function
Censored
Disease Free Survival of RT + Erb. + Cisplat.
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Impact on mucositis
� There is no reduction in the severity of mucositis with
IMRT. Mucositis is usually exaggerated in the area of
SIB to the primary site.
IMRT IN HEAD AND NECK CANCERS
SIB to the primary site.
� Upto 40% of patients need PEG insertion in patients
treated with IMRT + Concurrent CT
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Sparing of Submandibular gland with IMRT
�Mean threshold dose of SMG was 36 Gy
�Usually C/L SMG was spared
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Radiation + Erbitux in locally advanced Head & Neck Cancers –
Indian Experience (Aug 2005 – 2009)Indian Experience (Aug 2005 – 2009)
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Ca Alveolus Ca Alveolus 11 Inoperable Inoperable
Ca Buccal Mucosa Ca Buccal Mucosa 3 3 Surgery Refused Surgery Refused
Ca Ant 2/3 Tounge Ca Ant 2/3 Tounge 1010 Med. InoperableMed. Inoperable 11
UnresectableUnresectable 11
WLE + MRND WLE + MRND 22 High RiskHigh RiskPost OpPost OpMargins +ve Margins +ve
Tongue Commando Tongue Commando 33
TABLE -1 PATIENTS CHARACTERISTICS ( AUG 2005 – MAY 2009 )
(n=25)
Margins +ve Margins +ve nodes > 2 / ECE +venodes > 2 / ECE +veWLE ( Residual++) WLE ( Residual++) 11
Ca Base of TongueCa Base of Tongue 11
Ca OropharynxCa Oropharynx 11
Ca Pyriform FossaCa Pyriform Fossa 44
Ca Supralottic LarynxCa Supralottic Larynx 22
Ca Post CricoidCa Post Cricoid 11
Ca NasopharynxCa Nasopharynx 11
Ca Parotid Ca Parotid (Unresectable ) (Unresectable )
11
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N0N0 N1N1 N2N2 N3N3
T1T1 ---- ---- ---- ----
TABLE – 2 STAGE DISTRIBUTION ,(n=25)
STAGE IIB – 4T1T1 ---- ---- ---- ----
T2T2 11 22 11
T3T3 33 44 33
T4T4 33 55 22 11
STAGE IIB – 4STAGE III – 10STAGE IVA – 10STAGE iV B- 1
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CHEMOCHEMO--IMMUNOTHERAPY SCHEDULE IMMUNOTHERAPY SCHEDULE
Inj ERBITUXInj ERBITUX 400mg / m2400mg / m2 Day (Day (--7)7)
RADIATION AND CONCURRENT CETUXIMAB (ERBITUX) IN HNC
250mg / m2 250mg / m2 Weekly Weekly
Inj CISPLATINUM Inj CISPLATINUM + ERB+ ERB
35mg / m235mg / m2 Weekly Weekly
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DOSE:DOSE:-- RADIATION THERAPYRADIATION THERAPY
DOSE DELIVEREDDOSE DELIVERED
RADICALRADICALINTENTINTENT
CTVCTV 55.26 55.26 ---- 60.6Gy 60.6Gy 4 4 (old age, Prev Gamma knife)(old age, Prev Gamma knife)
CTVCTV 65.0 65.0 ---- 70.2 Gy70.2 Gy 1313
RADIATION AND CONCURRENTCETUXIMAB (ERBITUX) IN HNC
POSTPOSTOPERATIVEOPERATIVE
CTVCTV 54 54 ---- 60.6 Gy60.6 Gy 66
47* 47* ---- 52.0 Gy*52.0 Gy* 22
* preop/ re-radiation for 2nd malignancy
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RESPONSE ASSESSMENTRESPONSE ASSESSMENT
RT + ERB n=13RT + ERB n=13## RT + Cisp + ERB n=12RT + Cisp + ERB n=12
RESPONSE AT 3 MONTHSRESPONSE AT 3 MONTHS
CRCR *9 (69.23%)*9 (69.23%) **7 (58.33%)**7 (58.33%)
PRPR 33 44
PDPD ---- 11
RADIATION AND CONCURRENTCETUXIMAB (ERBITUX) IN HNC
SDSD ---- ------
STATUS AT LAST FOLLOW FU STATUS AT LAST FOLLOW FU
FOLLOW UP RANGEFOLLOW UP RANGE--: 2: 2--28 MONTHS,28 MONTHS, MEDIAN MEDIAN –– 13 MONTHS13 MONTHS
Alive NED Alive NED -- 88 Alive NED Alive NED --77
Alive with disease Alive with disease -- 22 Alive with disease Alive with disease -- 22
Died with disease Died with disease -- 33 Died with disease Died with disease -- 33
* Post Op 3/8* Post Op 3/8 **Post Op 4/7**Post Op 4/7# 1 pt LFU# 1 pt LFU
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Gr. II Skin rash
Gr. I - II Mucositis Radiotherapy + Cispl + Erb
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Grade I -Acne form rash
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Pro
babi
lity
of s
urvi
val (
%)
1.00
0.75
0.50
ERBITUX + RT: Overall Survival by Severity of Acne/Rash
ERBITUX + RT Grade 2-4 Acne/Rash
Time (Month)
Pro
babi
lity
of s
urvi
val (
%)
0 10 20 30 40 50 60 70
0.50
0.25
0.00
Bonner J.A, et al. as presented ASTRO 2008
ERBITUX + RT Grade 0-1 Acne/Rash
grade 0–1 grade 2-4n 81 127
Median 25.6 68.8+p=0.002HR (CI)= 0.49 (0.34 – 0.72)
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CA LT. UPPER ALVEOLUS WITH INTRACRANIAL
EXTENSION Treated with IMRT + ERBITUX
CT Showing GTV MRI Showing GTV at same
slice
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CA LT. UPPER ALVEOLUS WITH INTRACRANIAL EXTENSION
MRI Done 4 months later shows complete responsewith residual non enhancing thickening at the site of previous tumor
MRI & CT-PET- complete Response, NED till 36 months
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Cone Beam CT Image Planning CT Image
Tumor Shrinkage after 3 weeks of IMRTNote medical deviation of residual tumor parotid gl and and DARS
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Medical Deviation of Target Volume by 1.3cm
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• Instantly Ready Stereoscopic Imaging
• Bony anatomy or implanted markers
• Setup verification before and
during treatment (Snap Verification)
Image-Guided Radiation Therapy with ExacTrac
Fast, easy, precise daily positioning
• 6D patient setup (translations & rotations)
• Adaptive Gating
• System set-up accuracy 1mm 1
• Patient set-up accuracy 2mm 2,3
• May be used daily for all extracranial and
frameless radiosurgery patients
1) A phantom study on the pos. accuracy of the Novalis Body system. Yan H, et al.; Med. Phys. 30 (12), Dec.03: 3052–3060;
2) Image-Guided and IMRS for patients with Spinal Metastasis. Ryu S, et al.; CANCER April 03 / Vol.97;
3) A Technique for IMRS for Spinal Tumors. Yin F-F, et al.; Med. Phys. 29 (12), Dec.02: 2815–2822;
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Medial shift of Isodose curves due to Tumour shrinkage
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Weight loss,parotid gland shrinkage, and parotid centre- of-volume medial displacement during a course of radiation
therapy leads to an increase in the parotid gland mean dose. Red denotes 63Gy and yellow 26Gy.
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IMPACT OF IMRT
ON ON
XEROSTOMIA
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Anand et al: Clinical Oncology (2006) 18: 497 - 504
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IMPACT OF IMRT ON CHRONIC
DYSPHAGIA
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DYSPHAGIA RELATED ANATOMICAL STRUCTURES
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�23% experienced late Dysphagia Gr. III or IV
�Probability of swallowing disorders increased significantly
with dose to constrictor muscles- + 19% per 10Gy after
55Gy
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Anand et.al, British Journal of Radiology (2008) 81, 865-871
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Anand et.al, British Journal of Radiology (2008) 81, 865-871
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NAME: J. B
DATE: 21st JULY 2004, Post op Ca Tongue treated with IMRT
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NAME: COL. B.S CRNO: 48936, CA NASOPHARYNX, TREATED IN
DEC’ 2003 WITH IMRT + CT
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NAME: MRS. R. K, CRNO: 57793, IMRT BASE OF TONGUE,
Treated in Aug’2003
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Skin Fibrosis
• Grade 3 xerostomia ---11.8% ---- IMRT
53.4% ---- Conventional RT
• Grade 3 dysphagia -----0% ---- IMRT
26.7%---- Conventional RT (p=0.01)
• Skin Fibrosis ----- 0% ---- IMRT
26.7% ---- Conventional RT (p=0.03)
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Where do we go from here?
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Survival outcomes by HPV status RTOG 0129 study
• Phase III RTOG 0129 study in patients with stage II I-IV oropharyngeal cancer receiving standard FX or accelerated RT and cisplat in
• Survival data from 323 patients with HPV-evaluable tumors were analyzed
100
75
Ove
rall
surv
ival
(%
) HPV-positive
Ang et al. NEJM 2010
No at risk
HPV-positive 206 193 179 165 151 73
HPV-negative 117 89 76 65 51 22
75
50
25
00 1 2 3 4 5
Years since randomization
Ove
rall
surv
ival
(%
) HPV-positive
HPV-negative
HR=0.38 (95% CI: 0.26-0.55)p<0.001
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Three-year outcomes by HPV status RTOG 0129 study
Variable HPV-positive (%)
HPV-negative(%) p-value
Overall survival 82.4 57.1 <0.001
Progression-free survival
73.7 43.4 <0.001survival
Local-regional failure
13.6 35.1 <0.001
Distant metastases
8.7 14.6 0.23
Second primary tumor
5.9 14.6 0.02
Ang et al. NEJM 2010
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Oropharynx: Classification of patients intorisk-of-death categories
>10 pack -years≤10 pack -years>10 pack -years≤10 pack -years
HPV-positive(n=178)
HPV-negative(n=88)
Oropharyngeal cancer (n=266)
Recursive-partitioning analysis identified prognost ic factors with the most predictive significance
>10 pack -years(n=65)
≤10 pack -years(n=23)
>10 pack -years(n=90)
≤10 pack -years(n=88)
N0-N2a(n=26)
N2b-N3(n=64)
T2-T3(n=15)
T4(n=8)
42.9% at low risk3 year OS = 93.0%
27.4% at high risk3 year OS = 46.2%
29.7% at intermediate risk3 year OS = 70.8%
Ang et al. NEJM 2010
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Conclusions
• Treatment of locally advanced HNC is highlychallenging—Loco-regional control, long termmorbidity and organ conservation are importantconsiderations.
• Conc RT + CT is superior to Neo Adj CT foll by RT. Role• Conc RT + CT is superior to Neo Adj CT foll by RT. Roleof Induction CT is yet to be defined.
• Tumor HPV status is an independent prognostic factorfor OS and PFS
HPV-positive patients are at low risk, therefore may notneed to be subjected to the high toxicity of CRT (RTOG1016: RT + cisplatin vs RT + Erbitux)
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