Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams.
Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams.
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DOI：
10.18632/oncotarget.10996
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发表时间：
2016-08-30
期刊：
影响因子：
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通讯作者：
Abdollahi A
中科院分区：
文献类型：
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作者：
Dokic I;Mairani A;Niklas M;Zimmermann F;Chaudhri N;Krunic D;Tessonnier T;Ferrari A;Parodi K;Jäkel O;Debus J;Haberer T;Abdollahi A
全球越来越多的粒子治疗设施标志着精确肿瘤学的新时代。迫切需要实施强有力的生物物理读数，以评估不同辐射质量的功效。这是第一次报告的生物物理评价的蒙特卡罗模拟预测模型的处方剂量为四个粒子的质量，即，质子，氦，碳或氧离子使用光栅扫描技术和临床治疗设置在HIT。在计算机模拟、物理剂量测定和克隆性肿瘤细胞存活率之间发现了高度一致性。采用细胞荧光离子径迹混合检测器（Cell-Fit-HD）技术检测每个细胞核的粒子穿越。在研究的一组放射生物学替代物中，如晚期ROS积累和细胞凋亡（caspase 3/7激活），相对生物学效应（RBE）主要与辐射物种特异性DNA双链断裂（DSB）形成和修复动力学的时空模式相关。残留核γ-H2 AX灶的大小和数量随着线性能量转移（LET）和RBE的增加而增加，这让人联想到DNA损伤复杂性的增强和不可修复DSB的积累。这些数据证实了复杂DSB形成作为细胞命运的中心决定因素和细胞存活/RBE的可靠生物替代物的高度相关性。多尺度模拟，物理和放射生物学表征的新的临床质量光束在这里提出的高精度生物个体化放射治疗的发展迈出了第一步。
The growing number of particle therapy facilities worldwide landmarks a novel era of precision oncology. Implementation of robust biophysical readouts is urgently needed to assess the efficacy of different radiation qualities. This is the first report on biophysical evaluation of Monte Carlo simulated predictive models of prescribed dose for four particle qualities i.e., proton, helium-, carbon- or oxygen ions using raster-scanning technology and clinical therapy settings at HIT. A high level of agreement was found between the in silico simulations, the physical dosimetry and the clonogenic tumor cell survival. The cell fluorescence ion track hybrid detector (Cell-Fit-HD) technology was employed to detect particle traverse per cell nucleus. Across a panel of radiobiological surrogates studied such as late ROS accumulation and apoptosis (caspase 3/7 activation), the relative biological effectiveness (RBE) chiefly correlated with the radiation species-specific spatio-temporal pattern of DNA double strand break (DSB) formation and repair kinetic. The size and the number of residual nuclear γ-H2AX foci increased as a function of linear energy transfer (LET) and RBE, reminiscent of enhanced DNA-damage complexity and accumulation of non-repairable DSB. These data confirm the high relevance of complex DSB formation as a central determinant of cell fate and reliable biological surrogates for cell survival/RBE. The multi-scale simulation, physical and radiobiological characterization of novel clinical quality beams presented here constitutes a first step towards development of high precision biologically individualized radiotherapy.