Predictive models for potentiation of cell killing by combined exposure in vitro to photon radiation and BCNU

Cell killing potentiation by combined exposure to ionizing radiation and the cytotoxicant 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is of interest to radiation therapists because of implications to combined modality trials (radiation-therapy plus chemotherapy) for malignant gliomas. An additive-damage model is presented and used to predict cell killing potentiation after sequential exposure in vitro of rat 9L brain tumor cells to BCNU and X rays. Under the assumption of a Poisson distribution of lethal intracellular events, the average number of lethal lesions per cell can be represented by what is called the cumulative hazard. The cumulative hazard is used to arrive at a measure of cell-killing potentiation called the synergy factor (SF) which should be more sensitive than the conventional potentiation factor (PF) in the low-dose portion of the therapeutic dose range. Using a probabilistic modeling approach, it is shown that using cumulative hazards instead of doses to construct isobol curves, results similar to those arrived at with deterministic models for nonstochastic effects are obtained.