State Key Laboratory of Nuclear Physics and Technology, and Key Laboratory of HEDP of the Ministry of Education, Center for Applied Physics and Technology, Peking University, Beijing, China; New York Proton Center, New York, New York.
Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Int J Radiat Oncol Biol Phys. 2024 Nov 15;120(4):1181-1191. doi: 10.1016/j.ijrobp.2024.06.002. Epub 2024 Jun 14.
This study aimed to investigate a dose rate optimization framework based on the spot-scanning patterns to improve ultrahigh-dose-rate coverage of critical organs at risk (OARs) for proton pencil beam scanning (PBS) FLASH radiation therapy (ultrahigh dose-rate (often referred to as >40 Gy per second) delivery) and present implementation of a genetic algorithm (GA) method for spot sequence optimization to achieve PBS FLASH dose rate optimization under relatively low nozzle beam currents.
First, a multifield FLASH plan was developed to meet all the dosimetric goals and optimal FLASH dose rate coverage by considering the deliverable minimum monitor unit constraint. Then, a GA method was implemented into the in-house treatment platform to maximize the dose rate by exploring the best spot delivery sequence. A phantom study was performed to evaluate the effectiveness of the dose rate optimization. Then, 10 consecutive plans for patients with lung cancer previously treated using PBS intensity-modulated proton therapy were optimized using 45 GyRBE in 3 fractions for both transmission and Bragg peak FLASH radiation therapy for further validation. The spot delivery sequence of each treatment field was optimized using this GA. The ultrahigh-dose-rate-volume histogram and dose rate coverage V were investigated to assess the efficacy of dose rate optimization quantitatively.
Using a relatively low monitor unit/spot of 150, corresponding to a nozzle beam current of 65 nA, the FLASH dose rate ratio V of the OAR contour of the core was increased from 0% to ∼60% in the phantom study. In the patients with lung cancer, the ultrahigh-dose-rate coverage V was improved from 15.2%, 15.5%, 17.6%, and 16.0% before the delivery sequence optimization to 31.8%, 43.5%, 47.6%, and 30.5% after delivery sequence optimization in the lungs-GTV (gross tumor volume), spinal cord, esophagus, and heart (for all, P < .001). When the beam current increased to 130 nA, V was improved from 45.1%, 47.1%, 51.2%, and 51.4% to 65.3%, 83.5%, 88.1%, and 69.4% (P < .05). The averaged V for the target and OARs increased from 12.9% to 41.6% and 46.3% to 77.5% for 65 and 130 nA, respectively, showing significant improvements based on a clinical proton system. After optimizing the dose rate for the Bragg peak FLASH technique with a beam current of 340 nA, the V values for the lung GTV, spinal cord, esophagus, and heart were increased by 8.9%, 15.8%, 22%, and 20.8%, respectively.
An optimal plan quality can be maintained as the spot delivery sequence optimization is a separate independent process after the plan optimization. Both the phantom and patient results demonstrated that novel spot delivery sequence optimization can effectively improve the ultrahigh-dose-rate coverage for critical OARs, which can potentially be applied in clinical practice for better OARs-sparing efficacy.
本研究旨在基于点扫描模式探索一种剂量率优化框架，以提高质子笔形束扫描（PBS）FLASH 放疗中危及器官（OAR）的超高剂量率覆盖范围（超高剂量率（通常指每秒 >40Gy）），并提出一种遗传算法（GA）方法用于点序列优化，以实现在相对较低的喷嘴束流下 PBS FLASH 剂量率优化。
首先，通过考虑可交付的最小监测单位约束，开发了多野 FLASH 计划，以满足所有剂量学目标和最佳 FLASH 剂量率覆盖范围。然后，将 GA 方法实施到内部治疗平台中，通过探索最佳的点交付顺序来最大化剂量率。进行了体模研究以评估剂量率优化的有效性。然后，对 10 例先前使用 PBS 强度调制质子治疗的肺癌患者进行优化，对于透射和布拉格峰 FLASH 放疗，每个患者均接受 45GyRBE，分 3 次进行治疗。使用此 GA 对每个治疗野的点交付序列进行了优化。通过超高剂量率体积直方图和剂量率覆盖 V 来评估剂量率优化的效果，以定量评估剂量率优化的效果。
在体模研究中，使用相对较低的监测单位/点 150，对应的喷嘴束流为 65nA，OAR 轮廓的 FLASH 剂量率比从核心的 0%增加到约 60%。在肺癌患者中，超高剂量率覆盖 V 从肺-GTV（大体肿瘤体积）、脊髓、食管和心脏的 15.2%、15.5%、17.6%和 16.0%分别提高到 31.8%、43.5%、47.6%和 30.5%，在递送序列优化后（所有 P<0.001）。当束流增加到 130nA 时，V 从 45.1%、47.1%、51.2%和 51.4%提高到 65.3%、83.5%、88.1%和 69.4%（P<0.05）。靶区和 OARs 的平均 V 分别从 12.9%提高到 41.6%和从 46.3%提高到 77.5%，对于 65 和 130nA，分别显示出显著的改善，这是基于临床质子系统实现的。在用束流 340nA 优化布拉格峰 FLASH 技术的剂量率后，肺 GTV、脊髓、食管和心脏的 V 值分别增加了 8.9%、15.8%、22%和 20.8%。
在计划优化后，作为独立的处理过程进行点交付序列优化，可以保持优化计划的质量。体模和患者的结果均表明，新的点交付序列优化可以有效提高危及器官的超高剂量率覆盖范围，这可能在临床实践中应用于更好的 OAR 保护效果。
