Event-by-event approach to the oxygen-effect-incorporated stochastic microdosimetric kinetic model for hypofractionated multi-ion therapy

An oxygen-effect-incorporated stochastic microdosimetric kinetic (OSMK) model was previously developed to estimate the survival fraction of cells exposed to charged-particle beams with wide dose and linear energy transfer (LET) ranges under various oxygen conditions. In the model, hypoxia-induced radioresistance was formulated based on the dose-averaged radiation quality. This approximation may cause inaccuracy in the estimation of the biological effectiveness of the radiation with wide variation in energy deposited to a sensitive volume per event, such as spread-out Bragg peak (SOBP) beams. The purpose of this study was to apply an alternative approach so as to consider the energy depositions on an event-by-event basis. The production probability of radiation-induced lesions per energy was formulated with oxygen partial pressure to account for the hypoxia-induced radioresistance. The reduction in the oxygen enhancement ratio for high-LET radiations was modeled by reducing the sensitive-volume size and increasing the saturation energy in microdosimetry. The modified OSMK model was tested against the reported survival data of three cell lines exposed to six species of ions with wide dose and LET ranges under aerobic and hypoxic conditions. The model reasonably reproduced the reported cell survival data. To evaluate the event-by-event approach, survival distributions of Chinese hamster ovary cells exposed to SOBP beams were estimated using the original and modified OSMK models. The differences in the estimated survival distributions between the models were marginal even under extreme hypoxia. The event-by-event approach improved the theoretical validity of the OSMK model. However, the original OSMK model can still provide an accurate estimation of the biological effectiveness of therapeutic radiations.