A comprehensive model for heat-induced radio-sensitisation.

A comprehensive model for heat-induced radio-sensitisation.
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DOI:
10.1080/02656736.2017.1341059
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发表时间:
2018-06
期刊:
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
影响因子:
--
通讯作者:
Oelfke U
Oelfke U
中科院分区:
其他
文献类型:
--
作者:
Brüningk SC;Ijaz J;Rivens I;Nill S;Ter Haar G;Oelfke U

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联合放射治疗(RT)和热疗(HT)可通过热诱导放射增敏来改善治疗结果。我们提出了一个经验性的细胞存活模型(AlphaR模型)来描述这种多模式治疗。该模型的动机是观察到,热诱导的放射敏感性可能是通过受热细胞DNA损伤修复能力的降低来解释的。我们假设,这种修复只可能达到一个阈值水平,超过这个阈值,存活率将随着剂量的增加而指数下降。两个细胞系(HCT116,Cal27)的实验细胞存活数据与文献(幼年仓鼠肾[BHK]和中国仓鼠卵巢细胞[CHO])的细胞存活数据一起被考虑用于HT和联合RT-HT。克隆存活率与治疗温度和热剂量R2 ≥ 之间的关系采用AlphaR模型进行研究。对于HT生存曲线(0-80CEM43,43.5-57 °C),自由拟合AlphaR模型参数的数目可以减少到两个。这两个参数均随温度呈指数增长。基于我们的AlphaR模型,我们推导了不同温度下的相对生物有效性(RBE)或高温处理,以提供热剂量的另一种描述。对于组合RT-HT,我们的分析仅限于模型的线性二次臂。结果表明,在所用范围内(20-80CEM_(43),0-12 ),热剂量是热致辐射敏化的有效指标,模型参数可描述为热感生辐射敏化的函数。总体而言,提出的模型为描述细胞存活曲线提供了一个灵活的框架,并可能有助于更好地量化热诱导的放射敏感性,以及总体上的热剂量。
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.
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