Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment
Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment
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DOI：
10.1016/j.ijrobp.2014.05.010
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发表时间：
2014-09-01
影响因子：
7
通讯作者：
Schettino, Giuseppe
中科院分区：
文献类型：
--
作者：
Chaudhary, Pankaj;Marshall, Thomas I.;Schettino, Giuseppe
目的：只有通过详细评估沿布拉格曲线整个范围的相对生物有效性（RBE）变化，才能实现质子治疗的生物优化。临床上使用的 RBE 值 1.1 代表一个广泛的平均值，它忽略了扩展布拉格峰 (SOBP) 远端线性能量转移 (LET) 的急剧上升。特别关注细胞存活的关键终点，我们的工作使用人类正常细胞和抗辐射细胞，对沿单能（原始）和调制（SOBP）光束的细胞杀伤 RBE 变化进行了比较研究，旨在研究 RBE 对 LET 和固有放射敏感性的依赖性。方法和材料：人成纤维细胞（AG01522）和神经胶质瘤（U87）细胞 在 INFN-LNS（意大利卡塔尼亚）沿原始和调制 62 MeV 质子束在 6 个深度位置进行辐照。使用标准克隆形成测定法测量细胞杀伤 RBE 变化，并使用蒙特卡罗模拟和局部效应模型 (LEM) 进一步验证。结果：我们观察到沿质子束路径的显着细胞杀伤 RBE 变化，特别是在远端区域，显示出强烈的剂量依赖性。实验 RBE 值与 LEM 预测值非常一致，表明剂量平均 LET 作为质子生物有效性的合适预测因子。数据还用于验证参数化 RBE 模型。结论：根据从数据推断的变量 RBE，预测的递送至肿瘤区域的生物剂量与临床使用的恒定 RBE 1.1 相比存在显着差异。远端 RBE 的显着增加也表明有可能加强治疗方式的优化，例如缺氧肿瘤的 LET 涂敷。该研究强调了质子治疗采用恒定 RBE 的局限性，并提出了在治疗计划中快速实施 RBE 模型的方法。 (C) 2014 年爱思唯尔公司。
Purpose: The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate the RBE dependence on LET and intrinsic radiosensitvity.Methods and Materials: Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM).Results: We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton biological effectiveness. Data were also used to validate a parameterized RBE model.Conclusions: The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning. (C) 2014 Elsevier Inc.