Charyyev Serdar, Artz Mark, Szalkowski Gregory, Chang Chih-Wei, Stanforth Alexander, Lin Liyong, Zhang Rongxiao, Wang C-K Chris
Medical Physics Program, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Department of Radiation Oncology, Emory University, Atlanta, GA, 30322, USA.
Med Phys. 2020 Aug;47(8):3485-3495. doi: 10.1002/mp.14192. Epub 2020 May 11.
In this study, we investigated computationally and experimentally a hexagonal-pattern array of spatially fractionated proton minibeams produced by proton pencil beam scanning (PBS) technique. Spatial fractionation of dose delivery with millimeter or submillimeter beam size has proven to be a promising approach to significantly increase the normal tissue tolerance. Our goals are to obtain an optimized minibeam design and to show that it is feasible to implement the optimized minibeams at the existing proton clinics.
An optimized minibeam arrangement is one that would produce high peak-to-valley dose ratios (PVDRs) in normal tissues and a PVDR approaching unity at the Bragg peak. Using Monte Carlo (MC) code TOPAS we simulated proton pencil beams that mimic those available at the existing proton therapy facilities and obtained a hexagonal-pattern array of minibeams by collimating the proton pencil beams through the 1-3 mm diameter pinholes of a collimator. We optimized the minibeam design by considering different combinations of parameters including collimator material and thickness (t), center-to-center (c-t-c) distance, and beam size. The optimized minibeam design was then evaluated for normal tissue sparing against the uniform pencil beam scanning (PBS) by calculating the therapeutic advantage (TA) in terms of cell survival fraction. Verification measurements using radiochromic films were performed at the Emory proton therapy center (EPTC).
Optimized hexagonal-pattern minibeams having PVDRs of >10 at phantom surface and of >3 at depths up to 6 cm were achieved with 2 mm diameter modulated proton minibeams (with proton energies between 120 and 140 MeV) corresponding to a spread-out-Bragg-peak (SOBP) over the depth of 10-14 cm. The results of the film measurements agree with the MC results within 10%. The TA of the 2 mm minibeams against the uniform PBS is >3 from phantom surface to the depth of 5 cm and then smoothly drops to ~1.5 as it approaches the proximal edge of the SOBP. For 2 mm minibeams and 6 mm c-t-c distance, we delivered 1.72 Gy at SOBP for 7.2 × 7.2 × 4 cm volume in 48 s.
We conclude that it is feasible to implement the optimized hexagonal-pattern 2 mm proton minibeam radiotherapy at the existing proton clinics, because desirable PVDRs and TAs are achievable and the treatment time is reasonable.
在本研究中，我们通过计算和实验研究了利用质子笔形束扫描（PBS）技术产生的六边形图案排列的空间分割质子微束。已证明采用毫米或亚毫米束尺寸进行剂量递送的空间分割是一种显著提高正常组织耐受性的有前景的方法。我们的目标是获得优化的微束设计，并证明在现有的质子治疗中心实施优化后的微束是可行的。
优化的微束排列应能在正常组织中产生高的峰谷剂量比（PVDR），且在布拉格峰处的PVDR接近1。使用蒙特卡罗（MC）代码TOPAS，我们模拟了模仿现有质子治疗设施中可用的质子笔形束，并通过将质子笔形束通过准直器直径为1 - 3毫米的针孔进行准直，获得了六边形图案排列的微束。我们通过考虑包括准直器材料和厚度（t）、中心距（c - t - c）以及束尺寸等参数的不同组合来优化微束设计。然后通过计算细胞存活分数方面的治疗优势（TA），评估优化后的微束设计对均匀笔形束扫描（PBS）的正常组织保护效果。在埃默里质子治疗中心（EPTC）使用放射变色膜进行了验证测量。
对于直径为2毫米的调制质子微束（质子能量在120至140 MeV之间），在模体表面实现了PVDR大于10，在深度达6厘米处PVDR大于3，对应于在10 - 14厘米深度上的扩展布拉格峰（SOBP）。膜测量结果与MC结果在10%以内相符。2毫米微束相对于均匀PBS的TA在模体表面到5厘米深度处大于3，然后在接近SOBP近端边缘时平稳下降至约1.5。对于2毫米微束和6毫米的中心距，我们在48秒内为7.2×7.2×4厘米的体积在SOBP处递送了1.72 Gy。
我们得出结论，在现有的质子治疗中心实施优化后的六边形图案2毫米质子微束放射治疗是可行的，因为可以实现理想的PVDR和TA，且治疗时间合理。
