Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA.
Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, 53705, USA.
Med Phys. 2022 Apr;49(4):2684-2698. doi: 10.1002/mp.15523. Epub 2022 Feb 21.
The radiobiological benefits afforded by spatially fractionated (GRID) radiation therapy pairs well with the dosimetric advantages of proton therapy. Inspired by the emergence of energy-layer specific collimators in pencil beam scanning (PBS), this work investigates how the spot spacing and collimation can be optimized to maximize the therapeutic gains of a GRID treatment while demonstrating the integration of a dynamic collimation system (DCS) within a commercial beamline to deliver GRID treatments and experimentally benchmark Monte Carlo calculation methods.
GRID profiles were experimentally benchmarked using a clinical DCS prototype that was mounted to the nozzle of the IBA-dedicated nozzle system. Integral depth dose (IDD) curves and lateral profiles were measured for uncollimated and GRID-collimated beamlets. A library of collimated GRID dose distributions were simulated by placing beamlets within a specified uniform grid and weighting the beamlets to achieve a volume-averaged tumor cell survival equivalent to an open field delivery. The healthy tissue sparing afforded by the GRID distribution was then estimated across a range of spot spacings and collimation widths, which were later optimized based on the radiosensitivity of the tumor cell line and the nominal spot size of the PBS system. This was accomplished by using validated models of the IBA universal and dedicated nozzles.
Excellent agreement was observed between the measured and simulated profiles. The IDDs matched above 98.7% when analyzed using a 1%/1-mm gamma criterion with some minor deviation observed near the Bragg peak for higher beamlet energies. Lateral profile distributions predicted using Monte Carlo methods agreed well with the measured profiles; a gamma passing rate of 95% or higher was observed for all in-depth profiles examined using a 3%/2-mm criteria. Additional collimation was shown to improve PBS GRID treatments by sharpening the lateral penumbra of the beamlets but creates a trade-off between enhancing the valley-to-peak ratio of the GRID delivery and the dose-volume effect. The optimal collimation width and spot spacing changed as a function of the tumor cell radiosensitivity, dose, and spot size. In general, a spot spacing below 2.0 cm with a collimation less than 1.0 cm provided a superior dose distribution among the specific cases studied.
The ability to customize a GRID dose distribution using different collimation sizes and spot spacings is a useful advantage, especially to maximize the overall therapeutic benefit. In this regard, the capabilities of the DCS, and perhaps alternative dynamic collimators, can be used to enhance GRID treatments. Physical dose models calculated using Monte Carlo methods were experimentally benchmarked in water and were found to accurately predict the respective dose distributions of uncollimated and DCS-collimated GRID profiles.
空间分割（GRID）放射疗法带来的放射生物学益处与质子治疗的剂量学优势相得益彰。受铅笔束扫描（PBS）中出现的能量层特定准直器的启发，这项工作研究了如何优化光斑间距和准直度，以最大程度地提高 GRID 治疗的治疗效果，同时展示了在商业射束线上集成动态准直系统（DCS）以提供 GRID 治疗的能力，并通过实验基准测试了蒙特卡罗计算方法。
使用临床 DCS 原型对 GRID 剖面进行了实验基准测试，该原型安装在 IBA 专用喷嘴系统的喷嘴上。对未经准直和 GRID 准直的射束进行了积分深度剂量（IDD）曲线和横向轮廓测量。通过在指定的均匀网格中放置射束并对射束进行加权，模拟了具有 GRID 剂量分布的库。通过将射束放置在指定的均匀网格中并对射束进行加权，实现了体积平均肿瘤细胞存活量相当于开放场输送的效果，从而模拟了 GRID 剂量分布。在不同的光斑间距和准直宽度范围内估计了 GRID 分布对健康组织的保护作用，然后根据肿瘤细胞系的放射敏感性和 PBS 系统的标称光斑尺寸对其进行了优化。这是通过使用 IBA 通用和专用喷嘴的经过验证的模型来完成的。
测量和模拟的轮廓之间观察到极好的一致性。当使用 1%/1-mm 伽马标准进行分析时，IDDs 匹配度超过 98.7%，但在较高的射束能量下，在布拉格峰附近观察到一些较小的偏差。使用蒙特卡罗方法预测的横向轮廓分布与测量的轮廓吻合得很好；对于使用 3%/2-mm 标准检查的所有深度轮廓，观察到伽马通过率为 95%或更高。额外的准直可以通过锐化射束的横向半影来改善 PBS GRID 治疗，但会在增强 GRID 输送的谷峰比和剂量体积效应之间产生折衷。最佳准直宽度和光斑间距随肿瘤细胞放射敏感性、剂量和光斑尺寸而变化。一般来说，在研究的特定情况下，光斑间距小于 2.0cm 且准直小于 1.0cm 时，可以提供更好的剂量分布。
使用不同的准直尺寸和光斑间距定制 GRID 剂量分布的能力是一个有用的优势，尤其是可以最大限度地提高整体治疗效果。在这方面，DCS 的功能，也许还有其他动态准直器的功能，可以用于增强 GRID 治疗。在水中使用蒙特卡罗方法计算的物理剂量模型经过实验基准测试，发现可以准确预测未经准直和 DCS 准直的 GRID 剖面的相应剂量分布。
