基于同步加速器的质子与基于直线加速器的电子超高剂量率照射在急性胃肠道毒性方面的不一致性。

Discordance in Acute Gastrointestinal Toxicity between Synchrotron-Based Proton and Linac-based Electron Ultra-High Dose Rate Irradiation.

作者信息

Liu Kevin, Titt Uwe, Esplen Nolan, Connell Luke, Konradsson Elise, Yang Ming, Wang Xiaochun, Takaoka Takeshi, Li Ziyi, Koong Albert C, Mitra Devarati, Mohan Radhe, Loo Billy W, Lin Steven H, Schüler Emil

机构信息

Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas; The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, Texas.

Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas.

出版信息

Int J Radiat Oncol Biol Phys. 2025 Jun 1;122(2):491-501. doi: 10.1016/j.ijrobp.2025.01.007. Epub 2025 Jan 23.

DOI:10.1016/j.ijrobp.2025.01.007

PMID:39862897

Abstract

PURPOSE

Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate [ultra-high vs conventional (CONV)] and beam configuration [shoot-through (S-T) vs spread-out Bragg peak (SOBP)] on acute radiation-induced gastrointestinal toxicity (RIGIT) in mice. We also compared RIGIT between synchrotron-based protons and linac-based electrons with matched mean dose rates.

METHODS AND MATERIALS

We administered abdominal irradiation (12-14 Gy single fraction) to female C57BL/6J mice with an 87-MeV synchrotron-based proton beamline (2-cm-diameter field size as a lateral beam). Dose rates were 0.2 Gy/s (S-T pCONV), 0.3 Gy/s (SOBP pCONV), 150 Gy/s (S-T pFLASH), and 230 Gy/s (SOBP pFLASH). RIGIT was assessed by the jejunal regenerating crypt assay and survival. We also compared responses to proton (pFLASH and pCONV) with responses to electron CONV (eCONV, 0.4 Gy/s) and electron-beam FLASH (188-205 Gy/s).

RESULTS

The number of regenerating jejunal crypts at each matched dose was lowest for pFLASH (similar between S-T and SOBP), greater and similar between pCONV (S-T and SOBP) and eCONV, and greatest for electron-beam FLASH. Correspondingly, mice that received pFLASH SOBP had the lowest survival rates (50% at 50 days), followed by pFLASH S-T (80%), and pCONV SOBP (90%), but 100% of mice receiving pCONV S-T survived (log-rank P = .047 for the 4 groups).

CONCLUSIONS

Our findings are consistent with an increase in RIGIT after synchrotron-based pFLASH versus pCONV. This negative proton-specific FLASH effect versus linac-based electron irradiation underscores the importance of understanding the physical and biological factors that will allow safe and effective clinical translation.

摘要

目的

已使用回旋加速器和同步回旋加速器束线对质子FLASH进行了研究，但尚未使用同步加速器束线进行研究。我们评估了剂量率[超高与传统（CONV）]和射束配置[穿透式（S-T）与扩展布拉格峰（SOBP）]对小鼠急性辐射诱导的胃肠道毒性（RIGIT）的影响。我们还比较了基于同步加速器的质子与基于直线加速器的电子在匹配平均剂量率下的RIGIT。

方法和材料

我们使用基于87 MeV同步加速器的质子束线（2厘米直径的射野尺寸作为侧射束）对雌性C57BL/6J小鼠进行腹部照射（单次剂量12 - 14 Gy）。剂量率分别为0.2 Gy/s（S-T pCONV）、0.3 Gy/s（SOBP pCONV）、150 Gy/s（S-T pFLASH）和230 Gy/s（SOBP pFLASH）。通过空肠再生隐窝试验和存活率评估RIGIT。我们还比较了质子（pFLASH和pCONV）与电子CONV（eCONV，0.4 Gy/s）和电子束FLASH（188 - 205 Gy/s）的反应。

结果

在每个匹配剂量下，pFLASH的空肠再生隐窝数量最少（S-T和SOBP之间相似），pCONV（S-T和SOBP）与eCONV之间更多且相似，电子束FLASH的数量最多。相应地，接受pFLASH SOBP的小鼠存活率最低（50天时为50%），其次是pFLASH S-T（80%）和pCONV SOBP（90%），但接受pCONV S-T的小鼠100%存活（四组的对数秩检验P = 0.047）。