Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia.
German Cancer Research Center - DKFZ, Department of Medical Physics in Radiation Oncology, Heidelberg, Germany; Heidelberg Institute for Radiation Oncology - HIRO, Heidelberg, Germany.
Int J Radiat Oncol Biol Phys. 2023 Jul 15;116(4):949-959. doi: 10.1016/j.ijrobp.2023.01.048. Epub 2023 Feb 1.
Patient-specific ridge filters provide a passive means to modulate proton energy to obtain a conformal dose. Here we describe a new framework for optimization of filter design and spot maps to meet the unique demands of ultrahigh-dose-rate (FLASH) radiation therapy. We demonstrate an integrated physical optimization Intensity-modulated proton therapy (IMPT) (IPO-IMPT) approach for optimization of dose, dose-averaged dose rate (DADR), and dose-averaged linear energy transfer (LET).
We developed an inverse planning software to design patient-specific ridge filters that spread the Bragg peak from a fixed-energy, 250-MeV beam to a proximal beam-specific planning target volume. The software defines patient-specific ridge filter pin shapes and uses a Monte Carlo calculation engine, based on Geant4, to provide dose and LET influence matrices. Plan optimization, using matRAD, accommodates the IPO-IMPT objective function considering dose, dose rate, and LET simultaneously with minimum monitor unit constraints. The framework enables design of both regularly spaced and sparse-optimized ridge filters, from which some pins are omitted to allow faster delivery and selective LET optimization. To demonstrate the framework, we designed ridge filters for 3 example patients with lung cancer and optimized the plans using IPO-IMPT.
The IPO-IMPT framework selectively spared the organs at risk by reducing LET and increasing dose rate, relative to IMPT planning. Sparse-optimized ridge filters were superior to regularly spaced ridge filters in dose rate. Depending on which parameter is prioritized, volume distributions and histograms for dose, DADR, and LET, using evaluation structures specific to heart, lung, and esophagus, show high levels of FLASH dose-rate coverage and/or reduced LET, while maintaining dose coverage within the beam specific planning target volume.
This proof-of-concept study demonstrates the feasibility of using an IPO-IMPT framework to accomplish proton FLASH stereotactic body proton therapy, accounting for dose, DADR, and LET simultaneously.
患者特异性脊滤波器提供了一种被动的方法来调节质子能量，以获得适形剂量。在这里，我们描述了一种新的框架，用于优化滤波器设计和点图，以满足超高剂量率（FLASH）放射治疗的独特需求。我们展示了一种集成的物理优化强度调制质子治疗（IMPT）（IPO-IMPT）方法，用于优化剂量、剂量平均剂量率（DADR）和剂量平均线性能量传递（LET）。
我们开发了一种逆向规划软件，用于设计患者特异性脊滤波器，将来自固定能量 250 MeV 束的布拉格峰扩展到近端束特异性计划靶区。该软件定义了患者特异性脊滤波器销形状，并使用基于 Geant4 的蒙特卡罗计算引擎提供剂量和 LET 影响矩阵。使用 matRAD 的计划优化考虑了剂量、剂量率和 LET 的同时最小监视器单位约束的 IPO-IMPT 目标函数。该框架允许设计规则间隔和稀疏优化的脊滤波器，其中一些销被省略以允许更快的交付和选择性 LET 优化。为了演示该框架，我们设计了 3 例肺癌患者的脊滤波器，并使用 IPO-IMPT 对这些计划进行了优化。
与 IMPT 计划相比，IPO-IMPT 框架通过降低 LET 和增加剂量率选择性地保护了危及器官。稀疏优化的脊滤波器在剂量率方面优于规则间隔的脊滤波器。根据优先考虑的参数，使用心脏、肺和食管的特定评估结构的剂量、DADR 和 LET 的体积分布和直方图显示出高水平的 FLASH 剂量率覆盖和/或降低 LET，同时保持束特异性计划靶区内的剂量覆盖。
这项概念验证研究证明了使用 IPO-IMPT 框架同时考虑剂量、DADR 和 LET 来实现质子 FLASH 立体定向体部质子治疗的可行性。
