A biophysical model of cell survival in particle beam therapy combined with hyperthermia incorporating temperature and radiation quality

<i>Objective.</i>Hyperthermia (HT) is expected to enhance the biological effects of not only conventional radiotherapy but also particle beam therapy. However, a biophysical model that comprehensively considers both radiation quality (i.e. ion type and linear energy transfer, LET) and temperature has not yet been established. This study aimed to develop a model capable of calculating the cell-killing effect of particle beam therapy combined with HT.<i>Approach.</i>To incorporate temperature dependence into the stochastic microdosimetric kinetic (SMK) model, we hypothesized that sublethal lesion kinetics are temperature-dependent and that the thermal enhancement effect saturates at high LET. The resulting temperature-dependent SMK (TSMK) model was validated by fitting its parameters to published survival data from five Chinese hamster ovary cell lines treated with various radiation beams and subsequent HT.<i>Main results.</i>The TSMK model accurately reproduced the dose-survival curves for all five cell lines under both irradiation-alone and combined HT conditions. It also successfully replicated the LET dependence of the relative biological effectiveness (RBE) and thermal enhancement ratio (TER) for both highly and minimally thermosensitive cells. The TSMK model suggests that the LET dependence of TER is ion-type specific, similar to RBE. Furthermore, for cells treated with post-irradiation HT, the RBE and TER values rise at a lower LET compared to the RBE without HT.<i>Significance.</i>The TSMK model is the first biophysical model capable of calculating cell survival after combined irradiation with various beams and HT while accounting for dependencies on both radiation quality and temperature. This model is expected to be instrumental in optimizing treatment conditions and developing biologically-based treatment planning systems for particle beam therapy combined with HT.