New York Proton Center, New York, New York, USA.
Med Phys. 2022 Oct;49(10):6560-6574. doi: 10.1002/mp.15894. Epub 2022 Aug 17.
The transmission proton FLASH technique delivers high doses to the normal tissue distal to the target, which is less conformal compared to the Bragg peak technique. To investigate FLASH radiotherapy (RT) planning using single-energy Bragg peak beams with a similar beam arrangement as clinical intensity-modulated proton therapy (IMPT) in a liver stereotactic body radiation therapy (SBRT) and to characterize the plan quality, dose sparing of organs-at-risk (OARs), and FLASH dose rate percentage.
An in-house platform was developed to enable inverse IMPT-FLASH planning using single-energy Bragg peaks. A universal range shifter and range compensators were utilized to effectively align the Bragg peak to the distal edge of the target. Two different minimum MU settings of 400 and 800 MU/spot (Bragg-400 MU and Bragg-800 MU) plans were investigated on 10 consecutive hepatocellular carcinoma patients previously treated by IMPT-SBRT to evaluate the FLASH dose and dose rate coverage for OARs. The IMPT-FLASH using single-energy Bragg peaks delivered 50 Gy in five fractions with similar or identical beam arrangement to the clinical IMPT-SBRT plans. NRG GI003 dose constraint metrics were used. Three dose rate calculation methods, including average dose rate (ADR), dose threshold dose rate (DTDR), and dose-ADR (DADR), were all studied.
The novel spot map optimization can fulfill the inverse planning using single-energy Bragg peaks. All the Bragg peak FLASH plans achieved similar results for the liver-gross tumor volume (GTV) D and heart , compared to SBRT-IMPT. The Bragg-800 MU plans resulted in 18.3% higher clinical target volume (CTV) compared with SBRT (p < 0.05), and no significant difference was found between Bragg-400 MU and SBRT plans. For the CTV D , SBRT plans resulted in 10.3% (p < 0.01) less than Bragg-400 MU plans and 16.6% (p < 0.01) less than Bragg-800 MU plans. The Bragg-800 MU plans generally achieved higher ADR, DADR, and DTDR dose rates than Bragg-400 MU plans, and DADR mostly led to the highest V compared to other dose rate calculation methods, whereas ADR led to the lowest. The lower dose rate portions in certain OARs are related to the lower dose deposited due to the farther distances from targets, especially in the penumbra of the beams.
Single-energy Bragg peak IMPT-FLASH plans eliminate the exit dose in normal tissues, maintaining comparable dose metrics to the conventional IMPT-SBRT plans, while achieving a sufficient FLASH dose rate for liver cancers. This study demonstrates the feasibility of and sufficiently high dose rate when applying the Bragg peak FLASH treatment for a liver cancer hypofractionated FLASH therapy. The advancement of this novel method has the potential to optimize treatment for liver cancer patients.
传输质子 FLASH 技术可将高剂量输送至靶区远端的正常组织，与布拉格峰技术相比，其适形性较差。本研究旨在探讨使用与临床强度调制质子治疗（IMPT）相似的单次布拉格峰能束排列方式进行肝立体定向体部放射治疗（SBRT）的 FLASH 放疗（RT）计划，并对计划质量、危及器官（OAR）剂量节省和 FLASH 剂量率百分比进行特征描述。
开发了一种内部平台，以实现使用单能布拉格峰的逆向 IMPT-FLASH 计划。利用通用射程移位器和射程补偿器，可有效将布拉格峰对准靶区的远端边缘。在 10 例先前接受 IMPT-SBRT 治疗的肝细胞癌患者中，分别研究了两种不同的最小 MU 设置（400 和 800 MU/点（Bragg-400 MU 和 Bragg-800 MU）计划），以评估 OAR 的 FLASH 剂量和剂量率覆盖情况。IMP-FLASH 使用单能布拉格峰，以与临床 IMPT-SBRT 计划相似或相同的射束排列方式，在五部分中给予 50Gy。使用 NRG GI003 剂量限制指标。研究了三种剂量率计算方法，包括平均剂量率（ADR）、剂量阈值剂量率（DTDR）和剂量-ADR（DADR）。
新的点图优化可以满足使用单能布拉格峰进行逆向规划的要求。与 SBRT-IMPT 相比，所有的布拉格峰 FLASH 计划均能使肝脏-大体肿瘤体积（GTV）D 和心脏 获得相似的结果。与 SBRT 相比，Bragg-800 MU 计划使临床靶体积（CTV）增加了 18.3%（p<0.05），但 Bragg-400 MU 计划与 SBRT 计划之间无显著差异。对于 CTV D，SBRT 计划导致 10.3%（p<0.01）低于 Bragg-400 MU 计划和 16.6%（p<0.01）低于 Bragg-800 MU 计划。与 Bragg-400 MU 计划相比，Bragg-800 MU 计划通常能获得更高的 ADR、DADR 和 DTDR 剂量率，而 DADR 主要导致比其他剂量率计算方法更高的 V，而 ADR 导致最低的 V。某些 OAR 中的较低剂量率部分与靶区较远导致的剂量沉积较低有关，尤其是在射束的半影区。
单能布拉格峰 IMPT-FLASH 计划消除了正常组织中的出口剂量，与常规 IMPT-SBRT 计划保持可比的剂量指标，同时为肝癌提供足够的 FLASH 剂量率。本研究证明了在肝癌部分分割 FLASH 治疗中应用布拉格峰 FLASH 治疗的可行性和足够高的剂量率。该新方法的进展有可能优化肝癌患者的治疗。
