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

Abstract

Purpose: A therapeutic benefit can be achieved by hyperfractionation (HF) if tumours have small fractionation sensitivities characterized by alpha/beta values greater than those for late effects of dose limiting normal tissues. 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 the alpha/beta ratio were obtained from tumour control data from the randomized HF trials using the LQ model and a logit or probit type dose-response curve. A joint analysis of five randomized HF trials for head and neck carcinomas was performed to estimate overall alpha/beta and gamma50 values for tumour control. In addition, alpha/beta ratios for the individual trials were estimated using fixed gamma50 values (characteristic quantifying the steepness of dose-response curves) between 1.4 and 5 for tumours.

Results: An overall gamma50 of 3.1 (1.5-4.7) was estimated for the dose-tumour control relation from the HF trials, assuming a logit or probit dose-response curve. The tumours showed small fractionation sensitivities characterized by an overall alpha/beta of 10.5 (6.5-29) Gy. One trial allowed quantitative 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 gamma50 of 5 and was even smaller for smaller gamma50 values.

Conclusion: Head and neck carcinomas showed small fractionation sensitivities with alpha/beta values greater than those typical for bone, soft tissues, and skin, as well as steep dose response curves. Thus, important prerequisites for improving the therapeutic benefit of radiotherapy of head and neck carcinomas by HF are fulfilled for patients who met the accession criteria of the trials.