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.
Collections
Subject
Cell Line
Animals
Humans
DNA Damage
Combined Modality Therapy
Hyperthermia, Induced
Radiotherapy
DNA Repair
Models, Theoretical
Cricetinae
Hot Temperature
Research team
Radiotherapy Physics Modelling
Therapeutic Ultrasound
Language
eng
Date accepted
2017-06-06
License start date
2018-06
Citation
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2018, 34 (4), pp. 392 - 402
Publisher
TAYLOR & FRANCIS LTD