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: First report of RTOG 9003

Purpose: The optimal fractionation schedule for radiotherapy of head and ne ck cancer has been controversial. The objective of this randomized trial wa s to test the efficacy of hyperfractionation and two types of accelerated f ractionation individually against standard fractionation. Methods and Materials: Patients with locally advanced head and neck cancer were randomly assigned to receive radiotherapy delivered with: 1) standard fractionation at 2 Gy/fraction/day, 5 days/week, to 70 Gy/35 fractions/7 we eks; 2) hyperfractionation at 1.2 Gy/fraction, twice daily, 5 days/week to 81.6 Gy/68 fractions/7 weeks; 3) accelerated fractionation with split at 1. 6 Gy/fraction, twice daily, 5 days/week, to 67.2 Gy/42 fractions/6 weeks in cluding a 2-week rest after 38.4 Gy; or 4) accelerated fractionation with c oncomitant boost at 1.8 Gy/fraction/ day, 5 days/week and 1.5 Gy/fraction/d ay to a boost field as a second daily treatment for the last 12 treatment d ays to 72 Gy/42 fractions/6 weeks. Of the 1113 patients entered, 1073 patie nts were analyzable for outcome. The median follow-up was 23 months for all analyzable patients and 41.2 months for patients alive, Results: Patients treated with hyperfractionation and accelerated fractiona tion with concomitant boost had significantly better local-regional control (p = 0.045 and p = 0.050 respectively) than those treated with standard fr actionation, There was also a trend toward improved disease-free survival ( p = 0.067 and p = 0.054 respectively) although the difference in overall su rvival was not significant. Patients treated with accelerated fractionation with split had similar outcome to those treated with standard fractionatio n. All three altered fractionation groups had significantly greater acute s ide effects compared to standard fractionation, However, there was no signi ficant increase of late effects. Conclusions: Hyperfractionation and accelerated fractionation with concomit ant boost are more efficacious than standard fractionation for locally adva nced head and neck cancer. Acute but not late effects are also increased. ( C) 2000 Elsevier Science Inc.