Gao Hao, Lin Bowen, Lin Yuting, Fu Shujun, Langen Katja, Liu Tian, Bradley Jeffery
Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
School of Mathematics, Shandong University, Jinan, Shandong, China.
Med Phys. 2020 Dec;47(12):6388-6395. doi: 10.1002/mp.14531. Epub 2020 Nov 8.
FLASH radiotherapy (RT) can potentially reduce normal tissue toxicity while preserving tumoricidal effectiveness to improve the therapeutic ratio. The key of FLASH for sparing normal tissues is to irradiate tissues with an ultra-high dose rate (i.e., ≥40 Gy/s), for which proton RT can be used. However, currently available treatment plan optimization method only optimizes the dose distribution and does not directly optimize the dose rate. The contribution of this work to FLASH proton RT is the development of a novel treatment optimization method, that is, simultaneous dose and dose rate optimization (SDDRO), to optimize tissue-receiving dose rate distribution as well as dose distribution.
Distinguished from existing methods, SDDRO accounts for dose rate constraint and optimizes dose rate distribution. In terms of mathematical formulation, SDDRO is a constrained optimization problem with dose-volume constraint on dose distribution, minimum dose rate constraint on dose-averaged tissue-receiving dose rates, minimum monitor unit constraint on spot weight, and maximum intensity constraint on beam intensity. In terms of optimization algorithm, SDDRO is solved by iterative convex relaxation and alternating direction method of multipliers. SDDRO algorithms are presented for both scenarios with either constant or variable beam intensity.
SDDRO was compared with intensity modulated proton therapy (IMPT) (dose optimization alone, and no dose rate optimization) using three lung cases. SDDRO substantially improved the dose rate distribution compared to IMPT, for example, increasing of the region-of-interest (ROI) volume (ROI = CTV_10mm: the ring sandwiched by 10 mm outer and inner expansion of CTV boundary) receiving at least 40 Gy/s from ~30-50% to at least 98%, and the lung volume receiving at least 40 Gy/s from ~30-40% to ~70-90%. Moreover, both dose and dose rate distributions from SDDRO were further considerably improved via the combined use of hypofractionation and multiple beams.
We have developed a joint dose and dose rate optimization method for FLASH proton RT, namely SDDRO, which is first-of-its-kind to the best of our knowledge. The results suggest that (a) SDDRO can substantially improve the FLASH-dose rate coverage (e.g., in terms of dose rate volume histogram) compared to IMPT for the purpose of normal tissue sparing while preserving the dose distribution and (b) the combination of hypofractionation and multiple beams can further considerably improve the SDDRO plan quality in terms of both dose and dose rate distribution.
闪疗放疗（RT）有可能降低正常组织毒性，同时保持肿瘤杀伤效果以提高治疗比。闪疗保护正常组织的关键在于以超高剂量率（即≥40 Gy/s）照射组织，质子放疗可用于此。然而，目前可用的治疗计划优化方法仅优化剂量分布，并未直接优化剂量率。本研究对闪疗质子放疗的贡献在于开发了一种新的治疗优化方法，即同时剂量和剂量率优化（SDDRO），以优化组织接受的剂量率分布以及剂量分布。
与现有方法不同，SDDRO考虑了剂量率约束并优化剂量率分布。在数学公式方面，SDDRO是一个约束优化问题，具有剂量分布的剂量 - 体积约束、剂量平均组织接受剂量率的最小剂量率约束、射野权重的最小监测单位约束以及射束强度的最大强度约束。在优化算法方面，SDDRO通过迭代凸松弛和乘子交替方向法求解。针对射束强度恒定或可变的两种情况均给出了SDDRO算法。
使用三个肺部病例将SDDRO与调强质子治疗（IMPT）（仅剂量优化，无剂量率优化）进行比较。与IMPT相比，SDDRO显著改善了剂量率分布，例如，使感兴趣区域（ROI = CTV_10mm：CTV边界向外和向内扩展10 mm所夹的环）接受至少40 Gy/s的体积从约30 - 50%增加到至少98%，使肺部接受至少40 Gy/s的体积从约30 - 40%增加到约70 - 90%。此外，通过联合使用大分割放疗和多射束，SDDRO的剂量和剂量率分布均进一步得到显著改善。
我们开发了一种用于闪疗质子放疗的联合剂量和剂量率优化方法，即SDDRO，据我们所知这是首创。结果表明：（a）与IMPT相比，SDDRO在保护正常组织的同时，在保持剂量分布的情况下，可显著改善闪疗剂量率覆盖（例如，在剂量率体积直方图方面）；（b）大分割放疗和多射束的联合使用在剂量和剂量率分布方面均可进一步显著提高SDDRO计划质量。
