Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System
Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System
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DOI：
10.1016/j.ijrobp.2019.10.049
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发表时间：
2020-02-01
影响因子：
7
通讯作者：
Cengel, Keith A.
中科院分区：
文献类型：
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作者：
Diffenderfer, Eric S.;Verginadis, Ioannis I.;Cengel, Keith A.
目的：最近的研究表明，超高剂量率，“FLASH”，电子放射治疗（RT）减少正常组织损伤，同时保持肿瘤反应与传统的剂量率RT相比，在这里，我们描述了一种新的RT设备，提供闪光质子RT（PRT）使用双散射质子与计算机断层扫描引导，并提供质子闪光RT介导的正常组织辐射防护的第一份报告。方法和材料：在固体水中的多个深度处测量绝对剂量，并使用法拉第杯对绝对积分电荷测量进行验证。使用NaI探测器测量瞬发γ射线获得实时剂量率。使用胰腺侧腹肿瘤测量了FLASH与标准剂量率PRT对肿瘤和正常组织的影响在同系C57 BL/6 J小鼠中，使用源自KPC自体PanCa模型的MH 641905，分析腹部照射后小肠中的纤维化和干细胞再增殖。对双散射和准直装置进行了剂量学确认，FLASH和标准PRT的剂量率分别为78 +/- 9戈伊/秒和0.9 +/- 0.08戈伊/秒。与标准PRT相比，15戈伊的全腹FLASH PRT显著减少了肠隐窝中增殖细胞的损失。18戈伊的局部肠照射研究显示，与标准PRT相比，FLASH-PRT的肠纤维化降低至接近基线水平。尽管有这种差异，FLASH-PRT没有表现出肿瘤的放射保护在12或18戈伊irradiation.Conclusions后，在MH 641905胰腺癌侧翼肿瘤：我们已经设计和剂量验证了一个FLASH-PRT系统的准确控制束流在毫秒的时间尺度和在线监测的积分和剂量输送时间结构。使用该系统，我们发现FLASH-PRT减少了全腹和局灶性肠RT后的急性细胞丢失和晚期纤维化，而肿瘤生长抑制在2种模式之间保留。(C)2019年，任作家。爱思唯尔公司出版
Purpose: Recent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance and provide the first report of proton FLASH RT-mediated normal tissue radioprotection.Methods and Materials: Absolute dose was measured at multiple depths in solid water and validated against an absolute integral charge measurement using a Faraday cup. Real-time dose rate was obtained using a NaI detector to measure prompt gamma rays. The effect of FLASH versus standard dose rate PRT on tumors and normal tissues was measured using pancreatic flank tumors (MH641905) derived from the KPC autochthonous PanCa model in syngeneic C57BL/6J mice with analysis of fibrosis and stem cell repopulation in small intestine after abdominal irradiation.Results: The double scattering and collimation apparatus was dosimetrically validated with dose rates of 78 +/- 9 Gy per second and 0.9 +/- 0.08 Gy per second for the FLASH and standard PRT. Whole abdominal FLASH PRT at 15 Gy significantly reduced the loss of proliferating cells in intestinal crypts compared with standard PRT. Studies with local intestinal irradiation at 18 Gy revealed a reduction to near baseline levels of intestinal fibrosis for FLASH-PRT compared with standard PRT. Despite this difference, FLASH-PRT did not demonstrate tumor radioprotection in MH641905 pancreatic cancer flank tumors after 12 or 18 Gy irradiation.Conclusions: We have designed and dosimetrically validated a FLASH-PRT system with accurate control of beam flux on a millisecond time scale and online monitoring of the integral and dose delivery time structure. Using this system, we found that FLASH-PRT decreases acute cell loss and late fibrosis after whole-abdomen and focal intestinal RT, whereas tumor growth inhibition is preserved between the 2 modalities. (C) 2019 The Authors. Published by Elsevier Inc.