Modelling heat-induced radiosensitization: clinical implications

Clinically achievable minimum tumour temperatures are in the order of about 41°C. Therefore, it is important to evaluate mechanisms by which temperatures in this range might enhance cytotoxicity. Previous in vitro studies have demonstrated that 1–4 h (depending on the sequencing of modalities) of heating at 41°C produces substantial heat-induced radiosensitization with little or no cell killing by heat alone. The increased radiation sensitivity is best modelled as a change in the single hit, α, parameter (with no significant effect on the two-hit parameter, β) of the cell survival curve. The implications of heat-induced radiosensitization being mediated by a change in α on the traditional thermal enhancement ratio (for various radiation doses/fraction and α/β) are reviewed. Response rates for a cohort of 60 patients enrolled on a prospective thermal dose escalation study are modelled assuming that the thermal dose dependence of heat-induced radiosensitization is modulated by a heat-induced ▵α. The clinical data are fitted with ▵α about 0.05–0.1 Gy−1. Randomized trials reported in the literature and the implication for the design of future prospective trials are reviewed in light of these observations.