Altered fractionation in the management of head and neck cancer

Progress in radiation science led to the development of two classes of biologically sound fractionation schedules for the treatment of head and neck cancers. These altered fractionation regimens are referred to as hyperfractionation and accelerated fractionation schedules. Hyperfractionation exploits the difference in fractionation sensitivity between tumours and tissues manifesting late morbidity and only minor variations exist among regimens tested. In contrast, accelerated fractionation attempts to reduce tumour proliferation as a major cause of radiotherapy failure. Although there are major permutations, the existing schedules can conceptually be grouped into two categories, namely pure accelerated fractionation and hybrid accelerated regimens, depending on whether there are concurrent changes in other fractionation parameters. The results of completed phase III clinical trials addressing different types of altered fractionation schedules in head and neck carcinomas are summarized and examined in this review paper. The data from trials on hyperfractionation regimens applying 10-15% total dose increment consistently revealed a 10-15% improvement in the local control rate of a subset of intermediate-stage carcinomas without increasing the incidence of late complications. The available data on accelerated fractionation regimens already showed that tumour clonogen proliferation is a major cause of radiation failure. However, completed studies revealed that a 1-1.5 week treatment acceleration without total-dose reduction, achieved by administering 2 Gy fractions six times per week or concomitant boost schedule, yielded a ~ 15% higher tumour control rate without increasing late toxicity. Shortening the overall time to below 2 weeks with an associated total-dose reduction did not seem to improve the tumour control rate but might decrease some late normal-tissue injury. A weekly dose accumulation rate of ≤ 14 Gy or delivery of three fractions of 1.6 Gy per day, with a 6 h interval, without total-dose reduction was found to increase morbidity significantly. Further treatment refinements are being pursued based on these findings.