Accounting for and harnessing RBE variability in proton therapy

质子治疗中考虑和利用 RBE 变异性

• 批准号: 9751238
• 负责人: Oleg Vassiliev
• 金额: $ 28.08万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751238
• 关键词: Accounting; Affect; Biological; Childhood Ependymoma; Clinical; Computer Simulation; Computer software; Data; Data Analyses; Databases; Dimensions; Dose; Effectiveness; Elements; Foundations; Goals; Linear Energy Transfer; Location; Meta-Analysis; Methodology; Methods; Modeling; Normal tissue morphology; Outcome; Patients; Photons; Physical Function; Planning Techniques; Process; Protons; Publishing; Radiation therapy; Relative Biological Effectiveness; Research; Residual Tumors; Source; Structure; Therapeutic; Time; Tissues; Treatment outcome; Uncertainty; Variant; base; cancer radiation therapy; clinically relevant; clinically significant; cohort; density; experience; experimental study; ionization; phenomenological models; physical property; predictive tools; proton beam; proton therapy; spectral energy; tool; treatment planning; virtual clinical trial

The proposed study concerns proton beam radiotherapy of cancer. In the current standard of practice, treatment planning for proton therapy is based on the assumption that the relative biological effectiveness (RBE) of protons is 1.1 for all beam energies, dose levels and locations within the treated volume. Under this assumption, optimization of a treatment plan involves optimization of the physical dose only. However, it is well known that proton RBE is not constant. Abundant experimental data show unambiguously that the RBE increases with decreasing proton energy and with decreasing dose. Both these quantities vary within the treated volume and so does the RBE. This means that achieving an optimal distribution of the physical dose does not necessarily produce a treatment plan that is optimal in terms of the expected biological outcomes. The proposed study will develop a methodology and tools that will facilitate a new treatment plan optimization strategy that accounts for RBE variability, directly optimizes expected biological effects of a treatment, and thereby maximizes the likelihood of achieving best treatment outcomes. The main hypothesis of this study is that: Variations in proton RBE caused by variations of dose and beam energy spectrum can be modelled within uncertainties not exceeding those of experimental RBEs. The model can be incorporated in the treatment planning process so that for each patient a three dimensional RBE distribution is calculated. The computed RBEs will differ significantly from the generic RBE of 1.1 in clinically relevant structures. This hypothesis will be investigated by the following specific aims: 1. To develop a phenomenological model of RBE as a function of dose and beam energy spectrum. 2. To develop a proton treatment planning methodology where in addition to dose distribution, the variable RBE distribution is computed. 3. To investigate through treatment planning studies (in-silico or “virtual” clinical trials) the feasibility of the new methodology and to determine the potential clinical significance of RBE deviations from the generic RBE of 1.1.

拟议的研究涉及癌症的质子束放射治疗。 质子治疗的治疗计划基于以下假设：相对生物有效性 在此情况下，对于所有束流能量、剂量水平和处理体积内的位置，质子的 (RBE) 均为 1.1。 假设，治疗计划的优化仅涉及物理剂量的优化，但这很好。 已知质子 RBE 不是恒定的，大量实验数据明确表明 RBE。 随着质子能量的降低和剂量的降低而增加。 治疗体积和 RBE 也是如此，这意味着实现物理剂量的最佳分布。 不一定会产生就预期生物学结果而言最佳的治疗计划。 拟议的研究将开发一种方法和工具，以促进新的治疗计划 考虑 RBE 变异性的优化策略，直接优化预期的生物效应 治疗，从而最大限度地提高获得最佳治疗结果的可能性。 本研究的主要假设是： 剂量和束流变化引起质子 RBE 的变化 能谱可以在不超过实验 RBE 的不确定性范围内进行建模。 可以纳入治疗计划过程中，以便为每个患者提供三维 RBE 计算得出的 RBE 与临床中的通用 RBE 1.1 存在显着差异。 该假设将通过以下具体目标进行研究： 1. 开发一个 RBE 随剂量和束能谱变化的唯象模型 2. 开发质子。 治疗计划方法，除了剂量分布外，可变 RBE 分布为 3. 通过治疗计划研究（计算机模拟或“虚拟”临床试验）来调查可行性。 的新方法并确定 RBE 偏离通用方法的潜在临床意义 RBE 为 1.1。