A comprehensive model for heat-induced radio-sensitisation

Abstract

Combined radiotherapy (RT) and hyperthermia (HT) treatments may improve treatment outcome by heat induced radio-sensitisation. We propose an empirical cell survival model (AlphaR model) to describe this multimodality therapy. The model is motivated by the observation that heat induced radio-sensitisation may be explained by a reduction in the DNA damage repair capacity of heated cells. We assume that this repair is only possible up to a threshold level above which survival will decrease exponentially with dose. Experimental cell survival data from two cell lines (HCT116, Cal27) were considered along with that taken from the literature (baby hamster kidney [BHK] and Chinese hamster ovary cells [CHO]) for HT and combined RT-HT. The AlphaR model was used to study the dependence of clonogenic survival on treatment temperature, and thermal dose R² ≥ 0.95 for all fits). For HT survival curves (0–80 CEM43 at 43.5–57 °C), the number of free fit AlphaR model parameters could be reduced to two. Both parameters increased exponentially with temperature. We derived the relative biological effectiveness (RBE) or HT treatments at different temperatures, to provide an alternative description of thermal dose, based on our AlphaR model. For combined RT-HT, our analysis is restricted to the linear quadratic arm of the model. We show that, for the range used (20–80 CEM43, 0–12 Gy), thermal dose is a valid indicator of heat induced radio-sensitisation, and that the model parameters can be described as a function thereof. Overall, the proposed model provides a flexible framework for describing cell survival curves, and may contribute to better quantification of heat induced radio-sensitisation, and thermal dose in general.

Keywords:

• Linear quadratic model
• thermo-radio-sensitisation
• thermal dose
• radiation
• focused ultrasound

Acknowledgements

The authors thank the teams of Yuen-Li Chung and Sue Eccles for providing HCT116 and Cal27 cells. This work was supported financially by Cancer Research UK. Research at the Institute of Cancer Research is supported by Cancer Research UK under programme C33589/A19727. We thank the Focused Ultrasound Foundation for funding the work of Jannat Ijaz. We acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported financially by Cancer Research UK. Research at the Institute of Cancer Research is supported by Cancer Research UK under programme C33589/A19727. We thank the Focused Ultrasound Foundation for funding the work of Jannat Ijaz. We acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research.