De Mendoza, Adriana M. and Michlíková, Soňa and Berger, Johann and Karschau, Jens and Kunz-Schughart, Leoni A. and McLeod, Damian D. (2021) Mathematical model for the thermal enhancement of radiation response: thermodynamic approach. Scientific reports, 11 (1). pp. 1-14. ISSN 2045-2322

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Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

Item Type: Article
Subjects: Science and mathematics > Mathematics
Science and mathematics > Physics
Science and mathematics > Life sciences, biology
Date Deposited: 17 Feb 2022 14:37
Last Modified: 17 Feb 2022 14:37
URN: urn:nbn:de:gbv:715-oops-54005
DOI: 10.1038/s41598-021-84620-z

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