Investigating the effect of clonogen resensitization on the tumor response to fractionated external radiotherapy

In this work we further develop the modeling of tumor dynamics by proposing a mechanism of tumor resensitization that is based on the process of reoxygenation. Reoxygenation is modeled using the concept of nonstationary diffusion of oxygen. This leads to the derivation of an explicit expression for the radiosensitivity parameter that predicts a radiosensitivity that increases with time. To account for the resensitization mechanism, the time-dependent expression for the radiosensitivity is then incorporated within a tumor control probability (TCP) model that already includes tumor cell repopulation and repair. We fit a set of experimental animal TCP curves corresponding to several different fractionation regimes using both the modified (with resensitization) and unmodified (without resensitization) versions of the TCP model. In comparison to the unmodified model, the modified model produces statistically superior fits, and is able to describe an "inverse" dose-fractionation behavior present in the data.