AI 中文总结
研究评估基于pRF的肺癌SBRT计划在常规和FLASH剂量率下对免疫保护的作用。通过模拟和建模对比IMPT，发现pRF计划可缩短输送时间、减少血液照射剂量，改善循环淋巴细胞存活分数，为质子肺癌SBRT免疫保护提供实用策略。
AI 中文摘要
目的：辐射诱导的淋巴细胞减少是肺癌放疗中日益被认识到的一种毒性，且与循环淋巴细胞（CL）的辐射暴露有关。在调强质子治疗（IMPT）中，长时间的笔形束扫描（PBS）输送可能会增加CL的剂量。我们最近开发了一种针对患者的针状脊形滤过器（pRF）框架，可实现单束能量的超快速质子输送。本研究使用时间分辨血液剂量积累和CL存活模型，评估基于pRF的肺癌立体定向体部放疗（SBRT）计划在常规（pRFCONV）和FLASH剂量率（pRFFLASH）下是否能改善免疫保护。方法：为10例先前接受IMPT治疗的肺癌SBRT患者制定pRF计划。PBS输送模拟对束斑输送、扫描和能量切换进行建模。使用血液学剂量框架计算血液剂量体积直方图（bDVHs）。根据bDVHs，利用从CD4/CD8 CL的体外存活数据推导的饱和模型和线性二次模型估计CL存活分数（SF）。结果：与IMPT相比，pRFCONV/pRFFLASH计划减少了输送时间（平均减少：85.3/99.9%）和每分次照射的血液体积（平均减少：52.9/81.3%）。pRFCONV/pRFFLASH计划分别将血液V5cGy降低了26.4/39.4%，V50cGy降低了4.5/6.9%。pRF计划在所有模型和亚群中均改善了模拟的CL存活。未刺激的CD4/CD8 CL的SF差异最大，其中pRFCONV的平均饱和模型SF分别提高了7.9/8.6%（p = 0.03/0.02），pRFFLASH提高了9.6/10.4%（p = 0.02/0.01）。结论：pRF计划通过显著缩短输送时间和减少循环血液的照射，改善了模拟的CL存活。我们的研究结果表明，pRF的超快速输送可能为质子肺癌SBRT中的免疫保护提供一种实用策略。
英文摘要
Purpose: Radiation-induced lymphopenia is an increasingly recognized toxicity in lung radiotherapy and has been linked to radiation exposure to circulating lymphocytes (CL). In intensity-modulated proton therapy (IMPT), prolonged pencil beam scanning (PBS) delivery may increase CL dose. We recently developed a patient-specific pin ridge filter (pRF) framework that enables ultra-fast proton delivery with a single beam energy. This study evaluated whether pRF-based lung stereotactic body radiotherapy (SBRT) plans delivered at conventional (pRFCONV) and FLASH dose rates (pRFFLASH) improve immune sparing using time-resolved blood dose accumulation and CL survival modeling. Methods: pRF plans were created for 10 lung SBRT patients previously treated with IMPT. PBS delivery simulations modeled spot delivery, scanning, and energy switching. Blood dose-volume histograms (bDVHs) were calculated with the hematological dose framework. CL survival fractions (SF) were estimated from bDVHs with saturation and linear-quadratic models derived from in-vitro survival data for CD4/CD8 CL. Results: Compared with IMPT, pRFCONV/pRFFLASH plans reduced delivery time (mean reductions: 85.3/99.9%) and irradiated blood volume per fraction (mean reductions: 52.9/81.3%). pRFCONV/pRFFLASH plans reduced blood V5cGy by 26.4/39.4%, and V50cGy by 4.5/6.9%, respectively. pRF plans improved modeled CL survival across all models and subpopulations. Unstimulated CD4/CD8 CL had the largest SF differences, for which mean saturation-model SF improved by 7.9/8.6% for pRFCONV (p=0.03/0.02) and 9.6/10.4% for pRFFLASH (p=0.02/0.01), respectively. Conclusion: pRF plans improved modeled CL survival by significantly shortening delivery time and reducing irradiation of circulating blood. Our findings suggest that pRF's ultra-fast delivery may provide a practical strategy for immune sparing in proton lung SBRT.
Comments22 pages, 4 figures, 2 tables
