Department of Radiation Oncology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
Int J Radiat Oncol Biol Phys. 2013 Sep 1;87(1):216-22. doi: 10.1016/j.ijrobp.2013.05.013. Epub 2013 Jun 19.
To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT).
A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose-volume and LET-volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs.
The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation.
We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.
研究线性能量转移（LET）引导的计划优化在强度调制质子治疗（IMPT）中的可行性和潜在临床获益。
使用多标准优化（MCO）模块为 5 例头颈部癌症和 2 例胰腺癌患者生成一系列定义目标的帕累托最优 IMPT 基础计划（BP）。使用蒙特卡罗平台计算每个 BP 的剂量和 LET 分布。定制的 MCO 导航模块允许用户在 BP 之间进行插值，以生成可交付的帕累托最优解决方案。基于剂量-体积和 LET-体积直方图以及三维分布，评估每个患者 BP 之间的差异。使用基于 LET 的相对生物效应（RBE）模型评估在导航帕累托最优 BP 空间时的潜在临床获益。
对于头颈部患者，BP 之间的靶区平均 LET 值变化高达 30%，对于胰腺癌患者，BP 之间的平均 LET 值变化高达 14%。在危及器官（OARs）中变化更为明显，同一患者的 BP 之间的平均 LET 值差异高达 2 倍。通常观察到 OARs 的剂量和 LET 分布之间存在反比关系。考虑到 LET 依赖性可变 RBE 值，在 MCO 导航过程中，在几个研究结构上，RBE 加权剂量平均提高了 40%。
我们提出了一种优化质子治疗的新策略，以最大化肿瘤靶区的平均剂量-averaged LET，同时最小化正常组织结构的平均剂量-averaged LET。MCO BP 显示出显著的 LET 变化，导致 RBE 加权剂量可能存在显著差异。使用剂量和 LET 分布进行引导的帕累托表面导航提供了评估多种可交付计划的手段，并有助于确定临床最佳解决方案。
