On behalf of my RTOG investigator colleagues it is my privilege to present the long term outcomes of the RTOG H&N fractionation trial. This trial was begun more than 15 years ago and represents one of the largest purely fractionation trials ever conducted.
As you know there were 4 arms: SFX HFX w/ dose escal to 81.6 Gy, split course and concom boost.
Prim Obj was to improve local-regional control and a number of the usual secondary objectives.
Results were 1st reported in in 2000 by Karen Fu. For this report we have 5 years of additional follow-up for a median f/u of 8 years.The longest follow-up on any patient is 13.5 years. We also changed the time-based defn of late events from 90 to 180 days from start of therapy due to some prolonged acute events.
For this report we have 1068 analyzable patients; mostly oropharynx patients with only 10% oral cavity patients. Only 3% were stage II. Mostly stage II-IV using the 1988 staging system.
Kaplan-Meier local regional control showing about 7 points higher local-regional control for HFX and AFX-C. We did not include the split course are in these curves because I was similar to the standard arm and leaving it out make it easier to read.
Kaplan-Meier risk of developing at least 1 grade 3 or better late effect. Slight trend for higher risk with con com boost, but not stat signif at 0.18.
Prevalence of high grade late effects at years 1, 2, 5, 8 and 10. They tend to diminish over time and range from 6-24 %, depending on the year you look.
Risk of developing a second primary
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
RTOG Semi-Annual Meeting
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
Standard FractionationStandard Fractionation (SFX)(SFX)
Accelerated Hyperfractionation with SplitAccelerated Hyperfractionation with Split
Accelerated Fractionation ConcomitantAccelerated Fractionation Concomitant
oral cavity vs.
N- vs. N +
KPS 90-100 vs. 60-80
PrimaryPrimary:: To determine whether hyperfractionation and/or acceleratedTo determine whether hyperfractionation and/or accelerated
fractionation improve thefractionation improve the local-regional controllocal-regional control rate of advancedrate of advanced
squamous cell carcinoma of the head and neck.squamous cell carcinoma of the head and neck.
SecondarySecondary ::To evaluate the disease-free and overall survival ratesTo evaluate the disease-free and overall survival rates
associated with patients treated by each of the different fractionationassociated with patients treated by each of the different fractionation
schemes, and evaluate associated levels of acute and late treatmentschemes, and evaluate associated levels of acute and late treatment
Analyzable patientsAnalyzable patients 10731073 10681068
Median follow-up 3.4 yrs 8.5Median follow-up 3.4 yrs 8.5
Late events >90 d from start >180 dLate events >90 d from start >180 d
from startfrom start
Trotti (2005)Trotti (2005)Fu (2000)Fu (2000)
1113 patients entered; 1068 analyzable (96%)1113 patients entered; 1068 analyzable (96%)
Well balanced by gender, race, age, primary site, KPS, T-stagWell balanced by gender, race, age, primary site, KPS, T-stag
N-stage, stage groupN-stage, stage group
Oral cavityOral cavity 10.3%10.3%
SG LarynxSG Larynx 16.1%16.1%
AJCC Stage IIAJCC Stage II 3.4 % (BOT and HPX)3.4 % (BOT and HPX)
AJCC Stage IIIAJCC Stage III 28.3%28.3%
AJCC Stage IVAJCC Stage IV 68.3%68.3%
HFX 132/261 p=0.080
AFX-C 127/267 p=0.044
0 1 2 3 4 5 6 7 8 9 10
49% at 5 years (HFX & AFX-C)
42% at 5 years (SFX)
Causes of death
Complications of protocol treatment
Other causes & unknown
Prevalence of Grade 3+
YEARS FROM START OF RT
HFX RR=0.97 p=0.39
AFX-C RR=1.10 p=0.82
AHFX-S RR=1.04 p=0.72
1 2 5 8 10
n=218/arm* n=136/arm* n=76/arm * n=36/arm*
* Avg. No. Pts per arm
Time to Second Primary
0 1 2 3 4 5 6 7 8 9 10
25% at 5 years
40% at 10 years
• AFX-C (p=0.044) and HFX (p=0.080) 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
• 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 (p=0.18).
• 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 H&N; 4/5 are non-H&N
THANK YOUTHANK YOU
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
Medical College of Wisconsin
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
University of Rochester
Loyola Univ Medical Center
Johns Hopkins Hospital
University of Miami
Hamilton Regional Cancer Centre
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
Main Line Health CCOP
Christiana Care Health Services, Inc.
Columbia River CCOP
Upstate Carolina CCOP