A Radiation Therapy Oncology Group (RTOG) Phase III Randomized Study to Compare Hyperfractionation and Two Variants of Accelerated Fractionation to Standard Fractionation Radiotherapy for Head and Neck Squamous Cell Carcinomas: Preliminary Results of RTOG

James Metz, MD
OncoLink Associate Editor
Last Modified: November 1, 1999

Presenter: Karen K. Fu, MD
Affiliation: RTOG and University of California San Francisco

Summary:
Various fractionation schemes have been advocated for the treatment of head and neck cancer based on single institution experiences. This multi-institutional Phase III trial was performed to evaluate disease free survival, overall survival, local control and toxicities of each regimen.

Methods:
From 1991-1997, 1113 patients with advanced head and neck cancer were entered on the study. The most common primary site was oropharyngeal. Most patients had stage IV disease (64%). Patients were randomized to one of 4 arms in the trial:

Stantard fractionation (SF)of 70 Gy in 2 Gy fractions over 7 weeks
Hyperfractionation (HFX)81.6 Gy in 1.2 Gy fractions BID over 7 weeks
Accelerated fractionation with a split course (AFX-S)67.2 Gy at 1.6 Gy fractions BID over 6 weeks
Accelerated fractionation with a concomitant boost (AFX-C)72 Gy at 1.8 Gy fractions to a large field and 1.5 Gy fractions added as a boost each day on the last 12 treatment days.

Results:

The patients were well balanced between the four arms of the trial in pretreatment characteristics.
Local Regional Control was 46% (SF) vs 54% (HFX) vs 54% (AFX-C) vs 46% (AFX-S)
Two Year Disease Free Survival was 32% (SF) vs 38% (HFX) vs 39% (AFX-C) vs 33% (AFX-S)
There was no significant difference between the groups in regards to overall survival and distant metastatic rates
Acute RTOG Grade III toxicity was increased in all three altered fractionation regimens ranging from 51%-59% vs 35% for standard fractionation
AFX-C regimen had increased transient RTOG Grade III late toxicity but no difference in persistent toxicity when compared to the other regimens

Clinical/Scientific Implications:
The results of this altered fractionation trial have been highly anticipated by radiation oncologists. This trial will affect the design of all subsequent RTOG head and neck trials.

Local-regional control was significantly increased in the hyperfractionation arm (HFX) and the accelerated fractionation with concomitant boost arm (AFX-C)
There was no significant difference in overall survival between the groups
An analysis of the radiobiological implications revealed reducing the overall time of treatment by one week and keeping the total dose at 70 Gy or increasing the dose by 6 Gy may result in an increased local-regional control rate of approximately 10%
Because the AFX-C is logistically the easiest and most cost effective altered fractionation regimen it will be adopted as the control arm for all future RTOG head and neck trials

ASTRO coverage is sponsored, in part, by Varian Medical Systems, Inc.