Altered fractionation: limited by mucosal reactions?

The effectiveness of accelerated fractionation and hyperfractionation in ca ncer of the head and neck has been confirmed by randomized studies. These n ew fractionation strategies are almost invariably accompanied by an increas e of early normal tissue reactions, in particular mucosal reactions. This p aper presents a survey of the available experimental and clinical mucositis data and aims to assess to what extent the upper aerodigestive tract mucos a is limiting to treatment intensification by altered fractionation. The rate of dose delivery is the most important determinant for early radia tion reactions. With accelerated radiotherapy, relative to a conventional t reatment of 7 weeks, the achievable gain in treatment time is 2 weeks at mo st with the mucosa being the limiting tissue. Any further acceleration requ ires a reduction of dose. Manipulations with the temporal distribution of d ose, fraction dose, and optimization of interfraction intervals can improve tolerance but probably do not allow significant further intensification of the existing accelerated schedules. Dose escalation by hyperfractionation does not seem to be directly limited by early mucosal reactions. Late react ing tissues are more likely to limit intensification of these schedules. Suggestions for further improvement of treatment outcome include: the gener ation of a potent agent which can ameliorate radiation mucositis and so per mit further intensification of radiotherapy schedules; combination of alter ed fractionation schedules with hypoxic modifiers; and tailoring of the tre atment strategy based on patient and tumour characteristics. (C) 1999 Elsev ier Science Ireland Ltd. All rights reserved.