Accounting for and harnessing RBE variability in proton therapy

这项拟议的研究涉及癌症的质子束放射治疗。在目前的实践标准中， 质子疗法的治疗计划是基于这样的假设：相对生物有效性 对于所有束流能量、剂量水平和处理体积内的位置，质子的相对效率(RBE)为1.1。在这下面 假设，治疗计划的优化只涉及物理剂量的优化。然而，这是很好的 知道质子的相对分子质量不是恒定的。大量的实验数据明确地表明，RBE 随着质子能量的降低和剂量的减小而增加。这两个量在 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 就预期的生物结果而言，并不一定产生最佳的治疗计划。 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 因此，最大限度地提高了实现最佳治疗结果的可能性。 这项研究的主要假设是：剂量和束流的变化引起质子径向能量的变化 能谱可以在不超过实验RBE的不确定度内建模。模型 可以结合到治疗计划过程中，以便为每个患者提供三维RBE 计算了分布。在临床上，计算的RBE将显著不同于1.1的通用RBE 相关结构。这一假设将通过以下具体目标进行研究：1.开发一种 径向辐射效应随剂量和束能谱变化的唯象模型。2.发展质子 治疗计划方法，其中除了剂量分布之外，可变的RBE分布是 计算出来的。3.通过治疗计划研究(硅胶内或“虚拟”临床试验)调查可行性 并确定RBE偏离通用标准的潜在临床意义 RBE为1.1。

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.