Henthorn N T, Warmenhoven J W, Sotiropoulos M, Aitkenhead A H, Smith E A K, Ingram S P, Kirkby N F, Chadwick A L, Burnet N G, Mackay R I, Kirkby K J, Merchant M J
Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester UK
The Christie NHS Foundation Trust, Manchester Academic Health Science Centre Manchester UK.
RSC Adv. 2019 Feb 28;9(12):6845-6858. doi: 10.1039/c8ra10168j. eCollection 2019 Feb 22.
Relative Biological Effectiveness (RBE), the ratio of doses between radiation modalities to produce the same biological endpoint, is a controversial and important topic in proton therapy. A number of phenomenological models incorporate variable RBE as a function of Linear Energy Transfer (LET), though a lack of mechanistic description limits their applicability. In this work we take a different approach, using a track structure model employing fundamental physics and chemistry to make predictions of proton and photon induced DNA damage, the first step in the mechanism of radiation-induced cell death. We apply this model to a proton therapy clinical case showing, for the first time, predictions of DNA damage on a patient treatment plan. Our model predictions are for an idealised cell and are applied to an ependymoma case, at this stage without any cell specific parameters. By comparing to similar predictions for photons, we present a voxel-wise RBE of DNA damage complexity. This RBE of damage complexity shows similar trends to the expected RBE for cell kill, implying that damage complexity is an important factor in DNA repair and therefore biological effect.
相对生物效应（RBE）是指不同辐射方式产生相同生物学终点所需剂量的比值，是质子治疗中一个存在争议但很重要的话题。许多唯象模型将可变的RBE纳入其中，作为线性能量传递（LET）的函数，不过缺乏机理描述限制了它们的适用性。在这项工作中，我们采用了一种不同的方法，使用一个基于基础物理和化学的径迹结构模型来预测质子和光子诱导的DNA损伤，这是辐射诱导细胞死亡机制的第一步。我们将这个模型应用于一个质子治疗临床病例，首次展示了在患者治疗计划上对DNA损伤的预测。我们的模型预测是针对理想化细胞的，并应用于一个室管膜瘤病例，现阶段没有任何细胞特异性参数。通过与光子的类似预测进行比较，我们给出了DNA损伤复杂性的体素级RBE。这种损伤复杂性的RBE显示出与预期的细胞杀伤RBE相似的趋势，这意味着损伤复杂性是DNA修复以及因此也是生物学效应中的一个重要因素。
