Trotti, Andy 1 Fu, Karen K2 Pajak, Thomas F3 Jones, Christopher U4

1
Scientific Session RTOG Semi-Annual Meeting
Miami, Florida Saturday Jan 21, 2006
LONG TERM OUTCOMES OF RTOG 90-03 A COMPARISON
OF HYPERFRACTIONATION AND TWO VARIANTS OF
ACCELERATED FRACTIONATION TO STANDARD
FRACTIONATION RADIOTHERAPY FOR HEAD AND NECK
SQUAMOUS CELL CARCINOMA
Trotti, Andy 1 Fu, Karen K2 Pajak, Thomas F3
Jones, Christopher U4 Spencer, Sharon A5
Phillips, Theodore L2 Garden, Adam S9 Ridge,
John A7 Cooper, Jay S8 Ang, K Kian9
2
Standard Fractionation (SFX) Hyperfractionation
(HFX) Accelerated Hyperfractionation with Split
(AHFX-S)Accelerated Fractionation Concomitant
Boost (AFX-C)
Schema
S T R A T I F Y
oral cavity vs. oropharynx vs. larynx/hypopharynx
N- vs. N KPS 90-100 vs. 60-80
R
3
Primary To determine whether
hyperfractionation and/or accelerated
fractionation improve the local-regional control
rate of advanced squamous cell carcinoma of the
head and neck.Secondary To evaluate the
disease-free and overall survival rates
associated with patients treated by each of the
different fractionation schemes, and evaluate
associated levels of acute and late treatment
toxicities.
Objectives
4
Analyzable patients 1073 1068
Median follow-up 3.4 yrs
8.5 yrsLate events gt90 d
from start gt180 d from start
2005 analysis
Trotti (2005)
Fu (2000)
5
1113 patients entered 1068 analyzable (96)
Well balanced by gender, race, age, primary
site, KPS, T-stage, N-stage, stage groupOral
cavity 10.3Oropharynx 60.5Hypopharynx
13.1SG Larynx 16.1 AJCC Stage II 3.4
(BOT and HPX)AJCC Stage III 28.3AJCC Stage
IV 68.3
Patient characteristics
6
Local-Regional Control
7
Disease-Free Survival
8
Overall Survival
9
Causes of death
AFX-C 209 58.4 10.5 1.0 30.1
SFX 214 57.0 8.4 0.5 34.1
HFX 204 61.3 8.8 0.5 29.4
AHFX-S 219 56.6 12.3 0.5 30.6
Total dead Study cancer Second malignancy Complica
tions of protocol treatment Other causes unknown
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Time to Late Grade 3 Toxicity
11
Prevalence of Grade 3 Late Effects
WITH TOXICITY
n218/arm n136/arm
n76/arm n36/arm
n16/arm
1 2
5 8
10
Avg. No. Pts per arm
YEARS FROM START OF RT
12
Time to Second Primary
13
Conclusions

• AFX-C (p0.044) and HFX (p0.080) are assoc w/
  modestly higher loco-regional control (HR 0.80
  7 points).
• There is a trend for better disease-free survival
  in AFX-C and HFX.
• There are no differences in overall survival.

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Conclusions

• The risk of ever developing a grade 3 late event
  ranges from 33-44 at 5 years and 36-56 at 10
  years.
• The rate of late events is slightly higher with
  concomitant boost but not statistically
  significant (p0.18).
• Late event prevalence rates are similar among
  arms rates tend to decrease over time.
• The risk of developing a second malignancy is 25
  at 5 years and 40 at 10 years (1/5 are HN 4/5
  are non-HN sites).

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THANK YOU
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Participating Institutions
University of South Florida Radiological
Associates of Sacramento U. of Alabama at
Birmingham Medical Center University of
California San Francisco U. of Texas-MD Anderson
Cancer Center Fox Chase Cancer Center New York
University Hospital McGill University Medical
College of Wisconsin Washington
University Montefiore Medical Center University
of Western Ontario Akron City Hospital SUNY
Health Science Cntr/Brooklyn Wayne State
University University of Pennsylvania Medical
Center Dartmouth Hitchcock Medical Center Albert
Einstein Medical Center University of Puerto
Rico/Med Sciences Ca Emory University Affiliated
Hospitals University Of Alberta Thomas Jefferson
University Hospital
103 83 82 75 56 54 50 49 44 42 37 37 37 32 30 28 2
5 23 21 19 19 19
University of Rochester LDS Hospital Loyola Univ
Medical Center Johns Hopkins Hospital University
of Miami Hamilton Regional Cancer Centre Mayo
Clinic University of Kentucky Hospital South
Jersey Oncology Group CCOP Wake Forest University
Baptist Medical Center Kansas City CCOP S. Nevada
Cancer Research Foundation CCOP North Shore
University Hospital CCOP University of California
Davis Medical Center Greenville S.C. CCOP West
Michigan Cancer Center CCOP Atlanta Regional
CCOP Dayton CCOP Main Line Health CCOP Christiana
Care Health Services, Inc. Columbia River
CCOP Upstate Carolina CCOP
18 14 12 12 12 11 10 10 8 8 5 5 3 3 3 3 2 2 2 1 1
1
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LRC, DFS, DM and OS
 AFX-C
SFX
HFX
AFX-S
Locoregional Control 2yr 5yr 10yr
53 49 40
48 42 40
55 49 49
46 42 39
Disease Free Survival 2yr 5yr 10yr
31 20 11
34 23 15
38 25 13
38 26 11
Distant Metastasis 2yr 5yr 10yr
22 29 31
20 29 33
24 27 29
21 27 29
Overall Survival 2yr 5yr 10yr
55 37 18
47 29 19
46 30 17
49 34 19