Modelling heat-induced radiosensitization: clinical implications

• Published in: International journal of hyperthermia Vol. 20; no. 2; pp. 201 - 212
• Main Authors: Myerson, R. J., Roti, J. L. Roti, Moros, E. G., Straube, W. L., Xu, M.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.03.2004; Taylor & Francis
• Subjects: Animals; Combined Modality Therapy; heat-induced radiosensitization; Humans; Hyperthermia; Hyperthermia, Induced; Neoplasms - radiotherapy; radiation therapy; Radiation Tolerance
• ISSN: 0265-6736; 1464-5157
• DOI: 10.1080/02656730310001609353

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.