Mapping Proton RBE Variability Using Automated Biology and Monte Carlo Techniques

使用自动化生物学和蒙特卡罗技术绘制质子 RBE 变异性

• 批准号: 8887318
• 负责人: DAVID R GROSSHANS
• 金额: $ 17.4万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8887318
• 关键词: Affect; Anatomy; Applications Grants; Biological; Biology; Cell Culture Techniques; Cell Line; Clinical; Complex; Data; Dose; Effectiveness; Experimental Designs; Exposure to; Future; Goals; Health; Individual; Injury; Intensity modulated proton therapy; Knowledge; Lead; Linear Energy Transfer; Literature; Maps; Masks; Measurement; Measures; Methods; Mission; Modality; Modeling; Mono-S; National Cancer Institute; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Penetration; Process; Protons; Public Health; Radiation; Radiation Physics; Radiation therapy; Relative Biological Effectiveness; Research; Research Support; Resolution; Risk; Sampling; Scanning; Source; System; Techniques; Testing; Therapeutic; Therapeutic Index; Tumor Volume; Uncertainty; Variant; Work; base; cancer rehabilitation; cancer therapy; cell killing; cell type; clinically significant; cost; design; effective therapy; experience; flexibility; improved; innovation; irradiation; killings; neoplastic cell; novel; particle therapy; physical property; proton beam; proton therapy; treatment planning; treatment response

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.

描述（由申请人提供）：尽管涉及高成本，质子治疗中心的数量继续呈指数级增长。值得注意的是，即使新的中心上线，人们越来越意识到，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学有效性（RBE）随穿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RBE被简单地假设为1.1。这种假设可能导致RBE可能高于1.1的周围正常组织损伤风险增加。此外，利用更高的RBE来实现更大的肿瘤细胞杀伤的机会没有实现。到目前为止，几乎所有的临床质子治疗和生物测量RBE采用被动散射质子治疗（PSPT）。这可能掩盖了RBE可变性的重要性。利用原始扫描质子束进行的强度调制质子治疗（IMPT）被认为是质子治疗的未来。IMPT比目前流行的PSPT用途广泛得多。然而，对于真正的多场优化的IMPT，由各个射束贡献的物理剂量的高度不均匀性可能会受到RBE可变性的显著影响，并且即使是经验丰富的从业者也无法识别。另一方面，给定足够的知识，IMPT规划的固有灵活性可以允许将RBE空间变化并入治疗规划过程中，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子束的高RBE区域。我们研究的长期目标是提高我们对质子生物学效应的理解，并利用由此获得的知识来提高强度调制质子治疗的疗效。为了实现RBE优化的IMPT，从而扩大质子治疗的治疗指数，详细的空间数据RBE是迫切需要的，以指导逆向治疗计划过程。在目前的提议中，我们将使用单能扫描质子束，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）增强最近开发的系统，以系统和准确地绘制粒子治疗的生物学有效性，（2）基于高分辨率，高准确度的生物学数据，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。与其他研究仅专注于使用传统方法表征RBE相比，该提案的意义在于生成具有前所未有的空间分辨率的高度准确的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，并显着扩大粒子治疗的治疗率。

项目成果

Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques.

• DOI: 10.3390/cancers12123658
• 发表时间: 2020-12-05
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Bronk L;Guan F;Patel D;Ma D;Kroger B;Wang X;Tran K;Yiu J;Stephan C;Debus J;Abdollahi A;Jäkel O;Mohan R;Titt U;Grosshans DR
• 通讯作者: Grosshans DR

Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy.

• DOI: 10.1038/srep09850
• 发表时间: 2015-05-18
• 期刊: Scientific reports
• 影响因子: 4.6
• 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
• 通讯作者: Grosshans DR