José Santo Rodrigo, Habraken Steven J M, Breedveld Sebastiaan, Hoogeman Mischa S
Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, Rotterdam, The Netherlands; Instituto Superior Técnico, Department of Physics, Universidade de Lisboa, Lisbon, Portugal; Holland Proton Therapy Center, Department of Medical Physics & Informatics, Delft, The Netherlands.
Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, Rotterdam, The Netherlands; Holland Proton Therapy Center, Department of Medical Physics & Informatics, Delft, The Netherlands.
Int J Radiat Oncol Biol Phys. 2023 Mar 1;115(3):759-767. doi: 10.1016/j.ijrobp.2022.08.053. Epub 2022 Aug 31.
FLASH dose rates >40 Gy/s are readily available in proton therapy (PT) with cyclotron-accelerated beams and pencil-beam scanning (PBS). The PBS delivery pattern will affect the local dose rate, as quantified by the PBS dose rate (PBS-DR), and therefore needs to be accounted for in FLASH-PT with PBS, but it is not yet clear how. Our aim was to optimize patient-specific scan patterns for stereotactic FLASH-PT of early-stage lung cancer and lung metastases, maximizing the volume irradiated with PBS-DR >40 Gy/s of the organs at risk voxels irradiated to >8 Gy (FLASH coverage).
Plans to 54 Gy/3 fractions with 3 equiangular coplanar 244 MeV proton shoot-through transmission beams for 20 patients were optimized with in-house developed software. Planning target volume-based planning with a 5 mm margin was used. Planning target volume ranged from 4.4 to 84 cc. Scan-pattern optimization was performed with a Genetic Algorithm, run in parallel for 20 independent populations (islands). Mapped crossover, inversion, swap, and shift operators were applied to achieve (local) optimality on each island, with migration between them for global optimality. The cost function was chosen to maximize the FLASH coverage per beam at >8 Gy, >40 Gy/s, and 40 nA beam current. The optimized patterns were evaluated on FLASH coverage, PBS-DR distribution, and population PBS-DR-volume histograms, compared with standard line-by-line scanning. Robustness against beam current variation was investigated.
The optimized patterns have a snowflake-like structure, combined with outward swirling for larger targets. A population median FLASH coverage of 29.0% was obtained for optimized patterns compared with 6.9% for standard patterns, illustrating a significant increase in FLASH coverage for optimized patterns. For beam current variations of 5 nA, FLASH coverage varied between -6.1%-point and 2.2%-point for optimized patterns.
Significant improvements on the PBS-DR and, hence, on FLASH coverage and potential healthy-tissue sparing are obtained by sequential scan-pattern optimization. The optimizer is flexible and may be further fine-tuned, based on the exact conditions for FLASH.
在采用回旋加速器加速束流和笔形束扫描（PBS）的质子治疗（PT）中，可轻松实现大于40 Gy/s的FLASH剂量率。PBS的射野剂量分布模式会影响局部剂量率，可用PBS剂量率（PBS-DR）来量化，因此在采用PBS的FLASH-PT中需要考虑这一点，但目前尚不清楚具体方式。我们的目标是为早期肺癌和肺转移瘤的立体定向FLASH-PT优化特定患者的扫描模式，使照射剂量大于8 Gy的危及器官体素中PBS-DR大于40 Gy/s的照射体积最大化（FLASH覆盖范围）。
使用内部开发的软件对20例患者采用3个等角共面244 MeV质子穿透传输束进行54 Gy/3次分割的计划进行优化。采用基于计划靶区且外放5 mm边界的计划。计划靶区体积范围为4.4至84 cc。扫描模式优化采用遗传算法，针对20个独立种群（岛屿）并行运行。应用映射交叉、反转、交换和移位算子在每个岛屿上实现（局部）最优，并在它们之间进行迁移以实现全局最优。选择成本函数以最大化每束在大于8 Gy、大于40 Gy/s和40 nA束流时的FLASH覆盖范围。与标准逐行扫描相比，对优化后的模式在FLASH覆盖范围、PBS-DR分布和种群PBS-DR-体积直方图方面进行评估。研究了对束流变化的稳健性。
优化后的模式具有雪花状结构，对于较大靶区还伴有向外涡旋。优化模式的种群中位数FLASH覆盖范围为29.0%，而标准模式为6.9%，说明优化模式的FLASH覆盖范围显著增加。对于5 nA的束流变化，优化模式的FLASH覆盖范围在-6.1%-点至2.2%-点之间变化。
通过顺序扫描模式优化，在PBS-DR方面取得了显著改善，从而在FLASH覆盖范围和潜在的健康组织保护方面也有显著改善。该优化器具有灵活性，可根据FLASH的确切条件进一步微调。
