The effect of heterogeneity in tumor cell kinetics on radiation dose-response. An exploratory investigation of a plateau effect

Purpose: To investigate the effect of heterogeneity in tumor cell kinetics on radiation dose-response curves for a population of patients. Materials and methods: A series of exploratory calculations have been perfo rmed using an improved geometric-stochastic model of tumor cure. Results: Radiation therapy dose-response curves may plateau, or nearly so, at tumor control levels well below 100%, if a proportion of tumors would gr ow sufficiently fast to counterbalance the effect of fractionated radiother apy. If the model assumptions of doubling time heterogeneity are correct, t he difference between a short and protracted radiation regimen would be not only in the position and steepness of the radiation dose-response curve, b ut also in the level of the predicted plateau. Conclusions: For a given rate of dose accumulation, the one-sided flattenin g in dose-response curves at high doses is predicted from the modeling, and determined by the proportion of most radioresistant and rapidly growing tu mors. This shows that empirical models of tumor control probability which a ssume a symmetric sigmoid relationship from 0 to 100% have apparent limitat ions, seemingly not well acknowledged in the literature. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.