Quantification of chemotherapy contributions to chemoradiotherapy

Chemoradiotherapy (CRT) treatments are those which use chemotherapy drugs to improve the tumor control obtainable from radiotherapy schedules. Such additions are known to be beneficial and are widely prescribed. However, the methodologies employed for defining chemotherapy and radiation doses are entirely different, meaning that quantitative elucidation of the chemotherapy contribution to a CRT schedule remains difficult. One solution is to express the chemotherapy effect in terms of its radiation-equivalent and several authors have examined ways of doing this. This article outlines an approach which uses radiation-alone dose-response data as a platform against which to derive estimates of the drug contribution to CRT treatments. Such a methodology is potentially advantageous as radiation-alone parameters derived from observations of tumor response over a range of doses provide a realistic representation of whole-population behaviour and do not require prior assumptions to be made concerning radiosensitivity variations, etc. Although essentially a theoretical investigation. this approach provides some insight into how derived CRT dose-response curves can vary according to the possible modes of drug action, four of which are considered here, i.e. independent cell kill, dose sensitisation, reduced repopulation or combinations of each. It is shown that, for the moderate drug-induced TCP improvements usually observed in practice, the chemotherapy dose-equivalents derived from individual observations are a reasonable predictor of those operating at other levels of response, irrespective of the underlying drug-radiation synergy. •Use of radiation-alone dose-response data to determine radiation dose-equivalents of chemotherapy contributions to chemoradiotherapy.•To show how radiation-alone dose-response equations may be modified to take account of various chemotherapy enhancement mechanisms.•Examination of the variation in chemoradiotherapy dose-response characteristics for different drug-enhancement mechanisms.•Validity of using a derived chemotherapy dose-equivalent to predict chemoradiotherapy outcomes over a range of radiation doses.