Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy.
Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy.
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DOI：
10.1038/srep09850
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发表时间：
2015-05-18
影响因子：
4.6
通讯作者：
Grosshans DR
中科院分区：
文献类型：
--
作者：
Guan F;Bronk L;Titt U;Lin SH;Mirkovic D;Kerr MD;Zhu XR;Dinh J;Sobieski M;Stephan C;Peeler CR;Taleei R;Mohan R;Grosshans DR
在放射治疗中使用的粒子（例如质子）的物理性质已经被很好地表征，并且它们的剂量分布优于基于光子的治疗上级。然而，质子治疗也可能具有尚未充分利用的固有生物学优势。与光子束不同，粒子束的线性能量传递（LET）和生物学有效性沿束路沿着变化。选择性放置高效区域可以增强肿瘤细胞杀伤，同时保留正常组织。然而，以前用于绘制生物有效性空间变化的方法非常耗时，并且通常会产生不一致的结果，并且具有很大的不确定性。因此，需要准确地模拟相对生物学有效性，以指导新的治疗计划方法的数据是有限的。我们使用Monte Carlo建模和高含量的自动化克隆存活测定来空间映射扫描质子束的生物学有效性，具有高精度和高通量，同时最大限度地减少生物学不确定性。我们发现，细胞杀伤、剂量和LET之间的关系是复杂且非唯一的。测得的生物效应显著大于大多数以前的报告，即使对于最高的LET值，也观察到非线性存活分数反应。这种方法的扩展可以生成优化质子治疗计划所需的数据，包括可变RBE。
The physical properties of particles used in radiation therapy, such as protons, have been well characterized, and their dose distributions are superior to photon-based treatments. However, proton therapy may also have inherent biologic advantages that have not been capitalized on. Unlike photon beams, the linear energy transfer (LET) and hence biologic effectiveness of particle beams varies along the beam path. Selective placement of areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues. However, previous methods for mapping spatial variations in biologic effectiveness are time-consuming and often yield inconsistent results with large uncertainties. Thus the data needed to accurately model relative biological effectiveness to guide novel treatment planning approaches are limited. We used Monte Carlo modeling and high-content automated clonogenic survival assays to spatially map the biologic effectiveness of scanned proton beams with high accuracy and throughput while minimizing biological uncertainties. We found that the relationship between cell kill, dose, and LET, is complex and non-unique. Measured biologic effects were substantially greater than in most previous reports, and non-linear surviving fraction response was observed even for the highest LET values. Extension of this approach could generate data needed to optimize proton therapy plans incorporating variable RBE.