辐射响应热增强的数学模型：热力学方法
Mathematical model for the thermal enhancement of radiation response: Thermodynamic approach
摘要：
放射治疗可以有效地杀死恶性细胞，但治愈癌症患者所需的剂量可能会对邻近的健康组织造成严重的附带损害。热疗（HT）是改善放射治疗（RT）效果的一种有前途的选择，在医院中的应用越来越多。然而，同步热放疗的协同效应还没有得到很好的理解，而其数学建模是必不可少的治疗计划。为了更好地理解这种协同作用，我们提出了一个理论模型，其中的热增强比（TER）的解释是通过轻度HT的亚致死性损伤的施加放射增敏的细胞的分数。进一步的损伤最终会杀死细胞或抑制其在不可逆过程中的增殖。我们建议的TER是成比例的能源投资的敏化，这是一个简单的速率过程建模。假设蛋白质变性作为HT诱导的亚致死损伤的主要驱动力，并考虑到细胞蛋白质的热容量的温度依赖性，敏化率被认为是指数依赖于温度，与以前的经验观察。我们的预测很好地再现了体外和体内研究的实验数据，解释了同时热放疗的细胞放射反应的热调制。
英文摘要：
Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Hyperthermia (HT) is a promising option to improve the outcome of radiation treatment (RT) and is increasingly applied in hospital. However, the synergistic effect of simultaneous thermoradiotherapy is not well understood yet, while its mathematical modelling is essential for treatment planning. To better understand this synergy, we propose a theoretical model in which the thermal enhancement ratio (TER) is explained by the fraction of cells being radiosensitised by the infliction of sublethal damage through mild HT. Further damage finally kills the cell or inhibits its proliferation 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 predictions well reproduce experimental data from in-vitro and in-vivo studies, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.
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