Generalized mathematical model for adaptive cell survival after thermoradiotherapy: The impact of sublethal damage uri icon

Open Access

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Peer Reviewed

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Abstract

  • The efficacy of radiotherapy (RT) can be significantly enhanced by combination with hyperthermia (HT), offering improved therapeutic outcomes at reduced radiation doses. Recent technological advancements have revitalized HT as a promising option for combinatorial RT. However, the underlying mechanisms, implications, and cause-effect relationships require further elucidation for precise integration into clinical practice. In this context, mathematical modeling provides the necessary predicting power for treatment planning. Moreover, based on physicochemical principles, such models help elucidate the behavior of biological systems under heat. Some cell cultures exhibit dose-dependent changes in therapy response and survival, prompting the development of a model incorporating cell recovery mechanisms. We extended Jung's model of cellular inactivation by heat based on the accumulation of sublethal damage to combinatorial radiotherapy in general and incorporated dose-dependent recovery rates. The resulting unified model (Umodel) is suited to describe (i) individual or sequential treatment/fraction outcomes, (ii) differences and changes in cellular response and recovery or adaptation to treatment, and (iii) the observed sensitivity to treatment order. We demonstrate excellent performance (R2 > 0.95) on various cell survival data from the literature and our own experimental series. Our observations suggest that the induction of sublethal damage in cells is pivotal, promoting cellular vulnerability for synergistic outcomes in combined therapeutic schemes.