Bookbinder Alexander, Krieger Miriam, Lansonneur Pierre, Magliari Anthony, Zhao Xingyi, Choi J Isabelle, Simone Charles B, Lin Haibo, Folkerts Michael, Kang Minglei
New York Proton Center, New York, New York, USA.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
Med Phys. 2025 Jul;52(7):e17876. doi: 10.1002/mp.17876. Epub 2025 May 8.
Ultra-high dose rate, or FLASH, radiotherapy has shown promise in preclinical experiments of sparing healthy tissue without compromising tumor control. This "FLASH effect" can compound with dosimetric sparing of the proton Bragg peak (BP) using a method called Single Energy Pristine Bragg Peak (SEPBP) FLASH. However, this and other proposed FLASH techniques are constrained by lack of familiar treatment planning systems (TPSs). Creating modules to implement SEPBP FLASH into a commercial TPS opens up the possibility of more widespread investigation of FLASH and lays the groundwork for future clinical translation.
To implement, investigate, and benchmark the capacity of a commercial TPS research extension for BP FLASH SBRT treatment planning by studying the dosimetric properties and FLASH ratio for critical organs-at-risk (OARs) at several sites.
A 250 MeV clinical proton beam model was commissioned in the Eclipse TPS (Varian Medical Systems, Palo Alto, USA). BP FLASH fields were single-layer maximum-energy beams with a universal range shifter (URS) and field-specific range compensators (RCs). RCs for each beam angle were included as contours within the structure set, while the URS was modeled in the PBS beamline. Spotmaps were created using Lloyd's algorithm with minimum monitor units (MU)-based spacing to ensure plan quality and preserve FLASH coverage for critical OARs. Inverse optimization while preserving minimum MU constraints was done with scorecard-based optimization. Fifteen SBRT cases from three anatomical sites (liver, lung, base-of-skull [BOS]) previously treated at the New York Proton Center were re-optimized using this method, and dosimetric characteristics of BP plans were compared to clinically treated plans. FLASH ratios for critical OARs were evaluated for BP FLASH plans.
The dose distributions, including target uniformity, conformity index (CI), and DVHs, showed no significant difference in clinically-used metrics between BP FLASH and clinically delivered plans across all anatomical sites. Mean 40 Gy/s FLASH ratios for critical OARs were above 84% for all but one OAR with 2 Gy threshold and above 98% for all OARs with 5 Gy threshold. D for liver and BOS cases was 111.3 ± 2.68 and 112.88 ± 1.29, respectively, and D for lung cases was 112.04 ± 1.09. All D remained below 115%.
Inverse planning using a single-energy BP FLASH technique based on sparse spots and ultra-high minimum MU/spot can achieve intensity-modulated proton therapy (IMPT)-equivalent quality and sufficient FLASH coverage. This successful prototype brings us closer to commercial implementation and may increase the availability of proton FLASH dosimetry studies.
超高剂量率放疗，即FLASH放疗，已在临床前实验中展现出在不影响肿瘤控制的情况下保护健康组织的潜力。这种“FLASH效应”可与质子布拉格峰（BP）的剂量学保护相结合，采用一种名为单能原始布拉格峰（SEPBP）FLASH的方法。然而，这种以及其他提出的FLASH技术受到缺乏熟悉的治疗计划系统（TPS）的限制。创建将SEPBP FLASH应用于商业TPS的模块，为更广泛地研究FLASH开辟了可能性，并为未来的临床转化奠定了基础。
通过研究多个部位关键危及器官（OAR）的剂量学特性和FLASH比值，实现、研究并评估商业TPS研究扩展用于BP FLASH立体定向体部放疗（SBRT）治疗计划的能力。
在Eclipse TPS（美国瓦里安医疗系统公司，帕洛阿尔托）中调试了一个250 MeV临床质子束模型。BP FLASH射野是具有通用射程移位器（URS）和特定射野射程补偿器（RC）的单层最大能量束。每个射野角度的RC作为结构集中的轮廓包含在内，而URS在笔形束扫描（PBS）束线中建模。使用基于劳埃德算法的点图，以基于最小监测单位（MU）的间距来确保计划质量并为关键OAR保留FLASH覆盖范围。在保留最小MU约束的情况下，使用基于计分卡的优化进行逆向优化。对先前在纽约质子中心治疗的来自三个解剖部位（肝脏、肺、颅底[BOS]）的15个SBRT病例使用此方法重新优化，并将BP计划的剂量学特征与临床治疗计划进行比较。评估BP FLASH计划中关键OAR的FLASH比值。
剂量分布，包括靶区均匀性、适形指数（CI）和剂量体积直方图（DVH），在所有解剖部位的BP FLASH和临床实施计划之间的临床常用指标上没有显著差异。除一个2 Gy阈值的OAR外，关键OAR的平均40 Gy/s FLASH比值均高于84%，所有5 Gy阈值的OAR均高于98%。肝脏和BOS病例的D分别为111.3±2.68和112.88±1.29，肺部病例的D为112.04±1.09。所有D均保持在115%以下。
基于稀疏点和超高最小MU/点的单能BP FLASH技术的逆向计划可实现强度调制质子治疗（IMPT）等效质量和足够的FLASH覆盖。这个成功的原型使我们更接近商业应用，并可能增加质子FLASH剂量学研究的可用性。
