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

Abstract

To investigate the effect of heterogeneity in tumor cell kinetics on radiation dose-response curves for a population of patients. A series of exploratory calculations have been performed using an improved geometric-stochastic model of tumor cure. Radiation therapy dose-response curves may plateau, or nearly so, at tumor control levels well below 100%, if a proportion of tumors would grow sufficiently fast to counterbalance the effect of fractionated radiotherapy. If the model assumptions of doubling time heterogeneity are correct, the difference between a short and protracted radiation regimen would be not only in the position and steepness of the radiation dose-response curve, but also in the level of the predicted plateau. For a given rate of dose accumulation, the one-sided flattening in dose-response curves at high doses is predicted from the modeling, and determined by the proportion of most radioresistant and rapidly growing tumors. This shows that empirical models of tumor control probability which assume a symmetric sigmoid relationship from 0 to 100% have apparent limitations, seemingly not well acknowledged in the literature.