Radiation Therapy Oncology Group (RTOG) Altered Fractionation Trials

Abstract

The Radiation Therapy Oncology Group (RTOG) has been conducting clinical trials of altered fractionation radiotherapy since 1977. Altered fractionation schemes tested include hyperfractionation, several types of accelerated fractionation as well as hypofractionation. Initial trials were aimed at establishing the maximum tolerable dose using altered fractionation in various disease sites including head and neck, lung, brain, pelvis, and the gastrointestinal tract. Results of Phase I/U studies of hyperfraetionated radiotherapy clearly demonstrated that escalation of total doses to 15- 20% higher than those used in conventional fractionation can be achieved with acceptable acute toxicity and no significant increase of late toxicity. A dose-response relationship for tumor control was observed in head and neck cancer, non-small cell lung cancer and malignant gliomas. Daily interfraction interval ＜ 4.5 h was a significant risk factor for acute toxicity and late effects. Treatment interruption ＞ 5 days was detrimental to tumor control and survival. These studies have identified appropriate doses using hyperfractionation for comparison with standard fractionation, accelerated fractionation and other experimental treatments for the different disease sites. Phase III comparisons of hyperfractionation versus standard fractionation with or without chemotherapy have been completed in non-small cell lung cancer and malignant gliomas. For non-small cell lung cancer, induction chemotherapy followed by standard fractionated radiotherapy yielded better survival than hyperfractionated or standard fractionated radiotherapy alone. A Phase JIJ trial comparing hyperfractionation and BCNU to standard fractionation and I3CNU for malignant gliomas has completed patient accrual; results are not available yet. A Phase III comparison of standard fractionation and hyperfractionation and two variants of accelerated fractionation for head and neck cancer is in progress.