Mapping Proton RBE Variability Using Automated Biology and Monte Carlo Techniques

描述（由申请人提供）：尽管费用高昂，质子治疗中心的数量仍呈指数增长。值得注意的是，即使有新的中心上线，人们也越来越认识到，我们对质子生物学有效性的认识存在重大差距，这限制了质子治疗的临床潜力。文献中的一个共同主题是相对生物有效性（RBE）随着渗透深度和剂量的变化而变化。然而，在目前的实践中，在计算治疗的辐射剂量时，在所有情况下，简单地假设RBE为1.1。这一假设可能导致RBE高于1.1的周围正常组织损伤的风险增加。而且，没有机会利用更高的RBE来实现对肿瘤细胞的更大杀伤。迄今为止，几乎所有临床质子治疗和RBE的生物学测量都采用被动散射质子治疗（PSPT）。这可能掩盖了RBE变异性的重要性。以原始扫描质子束传输的调强质子治疗（IMPT）被认为是质子治疗的未来。IMPT比目前流行的PSPT更通用。然而，对于真正的多场优化IMPT，单个光束贡献的物理剂量的高度不均匀性可能会受到RBE变变性的很大影响，即使是经验丰富的从业者也无法识别。另一方面，如果有足够的知识，IMPT计划固有的灵活性可能允许将RBE空间变化纳入治疗计划过程，潜在地增加生物有效靶剂量，同时减少正常组织暴露于每个光束的高RBE区域。我们研究的长期目标是提高我们对质子生物学有效性的理解，并利用由此获得的知识来提高强度调制质子治疗的疗效。为了完成RBE优化的IMPT，从而扩大质子治疗的治疗指标，迫切需要关于RBE的详细空间数据，以指导逆治疗计划过程。在目前的建议中，我们将使用单能量扫描质子束，这是一种基于辐射传输物理学和高通量生物技术的创新实验设计。以下目标将为实现我们的长期目标提供必要的数据；(1)加强最近开发的系统，以系统准确地绘制粒子治疗的生物学效果；(2)基于高分辨率、高精度的生物学数据，提高我们对RBE变异性的理解；(3)研究空间RBE变异性的潜在生物学和临床后果。与其他研究仅关注于传统方法表征RBE相比，本研究的意义在于生成了具有前所未有空间分辨率的高精度RBE数据。这些数据将允许将可变的生物有效性纳入IMPT治疗计划，并显着扩大颗粒治疗的治疗比例。

DESCRIPTION (provided by applicant): Despite the high costs involved, the number of proton therapy centers continues to increase exponentially. Remarkably, even as new centers come on line, there is increasing realization that there are significant gaps in our knowledge of the biologic effectiveness of protons, which limit the clinical potential of proton therapy. One common theme in the literature is that relative biologic effectiveness (RBE) varies substantially as a function of depth of penetration and dose. Yet, in current practice RBE is simplistically assumed to be 1.1 in all situations while computing radiation dose for treatments. This assumption may lead to an increased risk of injury to surrounding normal tissues where RBE may be higher than 1.1. Moreover, the opportunity to take advantage of the higher RBE to achieve greater killing of tumor cells is not realized. To date virtually all clinical proton treatments and biologic measurements of RBE have employed passive scattering proton therapy (PSPT). This has likely masked the importance of RBE variability. Intensity-modulated proton therapy (IMPT) delivered with pristine scanned proton beams is considered to be the future of proton therapy. IMPT is much more versatile than currently prevalent PSPT. However, for true multi-field optimized IMPT the high inhomogeneity of physical dose contributed by individual beams may be substantially affected by RBE variability and go unrecognized even by experienced practitioners. On the other hand, given sufficient knowledge, the inherent flexibility of IMPT planning may allow for the incorporation of RBE spatial variation into the treatment planning process, potentially increasing biologically effective target dose while simultaneously decreasing normal tissue exposure to high RBE regions of each beamlet. The long-term goals of our research are to improve our understanding of the biological effectiveness of protons and to employ the knowledge thus acquired to enhance the efficacy of intensity modulated proton therapy. In order to accomplish RBE optimized IMPT and thereby expand the therapeutic index of proton therapy, detailed spatial data concerning RBE is desperately needed in order to guide the inverse treatment planning process. In the current proposal we will use mono-energetic scanned proton beams, an innovative experimental design based on the physics of radiation transport and high- throughput biological techniques. The following aims will provide data essential for achieving our long-term goals; (1) Enhance a recently developed system for systematically and accurately mapping the biologic effectiveness of particle therapy, (2) Improve our understanding of the variability of RBE based on high- resolution, high accuracy biologic data, (3) Investigate the potential biologic and clinical consequences of spatial RBE variability. In contrast to other studies focusing solely on characterizing RBE using traditional methods, the significance of this proposal lies in generating highly accurate RBE data with unprecedented spatial resolution. Such data will allow for the incorporation of variable biologic effectiveness ito IMPT treatment planning and dramatically expand the therapeutic ratio of particle therapy.