Fractionation sensitivities and dose-control relations of head and neck carcinomas: analysis of the randomized hyperfractionation trials

Purpose: A therapeutic benefit can be achieved by hyperfractionation (HF) i f tumours have small fractionation sensitivities characterized by alpha/bet a values greater than those for late effects of dose limiting normal tissue s. It is the purpose of the present paper to estimate alpha/beta values for head and neck carcinomas from randomized HF trials. Materials and methods: Maximum likelihood estimates of the alpha/beta ratio were obtained from tumour control data from the randomized HF trials using the LQ model and a legit or probit type dose-response curve. A joint analy sis of five randomized HF trials for head and neck carcinomas was performed to estimate overall alpha/beta and gamma 50 values for tumour control. In addition, alpha/beta ratios for the individual trials were estimated using fixed gamma 50 values (characteristic quantifying the steepness of dose-res ponse curves) between 1.4 and 5 for rumours. Results: An overall gamma 50 of 3.1 (1.5-4.7) was estimated for the dose-tu mour control relation from the HF trials, assuming a legit or probit dose-r esponse curve. The tumours showed small fractionation sensitivities charact erized by an overall alpha/beta of 10.5 (6.5-29) Gy. One trial allowed quan titative estimation of the alpha/beta values for late normal tissue damage: The alpha/beta estimate for late effects of grade 2 + was 4.0 (3.3-5.0) Gy , assuming a fixed gamma 50 of 5 and was even smaller for smaller gamma 50 values. Conclusion: Head and neck carcinomas showed small fractionation sensitiviti es with alpha/beta values greater than those typical for bone, soft tissues , and skin, as well as steep dose response curves. Thus, important prerequi sites for improving the therapeutic benefit of radiotherapy of head and nec k carcinomas by HF are fulfilled for patients who met the accession criteri a of the trials. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved .