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

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.

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.


  • 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

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