重新定义闪光辐射疗法：胃肠道平均剂量速率和每个脉冲剂量的影响
Redefining FLASH Radiation Therapy: The Impact of Mean Dose Rate and Dose Per Pulse in the Gastrointestinal Tract
影响因子:6.50000
分区:医学1区 Top / 肿瘤学2区 核医学2区
发表日期:2025 Mar 15
作者:
Kevin Liu, Trey Waldrop, Edgardo Aguilar, Nefetiti Mims, Denae Neill, Abagail Delahoussaye, Ziyi Li, David Swanson, Steven H Lin, Albert C Koong, Cullen M Taniguchi, Billy W Loo, Devarati Mitra, Emil Schüler
摘要
对变化辐射束参数设置的理解影响闪光效应的诱导和幅度仍然有限。 We sought to systematically evaluate how the magnitude of radiation-induced gastrointestinal toxicity depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP).C57BL/6J mice received total abdominal irradiation (TAI, 11-14 Gy single fraction) through either conventional (CONV) irradiation (low-DPP and low MDR, CONV) or through various combinations of DPP and MDR up to超高剂量率梁条件。评估了1至6 Gy的DPP，而总剂量和MDR（> 100 gy/s）保持恒定；评估了MDR的效果为0.3至1440 Gy/s，而总剂量和DPP保持恒定。通过再生地下室分析和生存评估，在非肿瘤的小鼠中量化了辐射诱导的胃肠道毒性。通过肿瘤的生长延迟评估肿瘤反应。使用恒定的MDR（> 100 Gy/s）测试的总剂量，增加了DPP的增加导致保留量的增加（重生地下室的数量增加），在12-和14 gy Tai时看到了更突出的效果。有趣的是，在> 4 Gy的DPP中，与使用的MDR无关（从0.3到1440 gy/s），也证明了类似水平的隐窝弹出水平。在4.7 Gy的固定高DPP下，与CONC相比，生存率等效地相当于MDR。但是，在较低的DPP为0.93 Gy时，与0.3 Gy/s相比，104 Gy/s的MDR产生了更大的生存效应。我们还确认，使用临床相关的黑色素瘤小鼠模型，高滴滴淋加剂，无论MDR如何，都产生了相同的肿瘤生长延迟。这项研究表明，梁参数设置对闪光效应的幅度的强烈影响。高DPP和超高剂量率似乎是独立的，足以产生胃肠道毒性的闪光，同时在所有条件下都保持了同配肿瘤的反应。
Abstract
The understanding of how varying radiation beam parameter settings affect the induction and magnitude of the FLASH effect remains limited. We sought to systematically evaluate how the magnitude of radiation-induced gastrointestinal toxicity depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP).C57BL/6J mice received total abdominal irradiation (TAI, 11-14 Gy single fraction) through either conventional (CONV) irradiation (low-DPP and low MDR, CONV) or through various combinations of DPP and MDR up to ultra-high-dose-rate beam conditions. DPPs ranging from 1 to 6 Gy were evaluated, while the total dose and MDR (>100 Gy/s) were kept constant; the effects of MDR were evaluated for the range of 0.3 to 1440 Gy/s, while the total dose and DPP were kept constant. Radiation-induced gastrointestinal toxicity was quantified in nontumor-bearing mice through the regenerating crypt assay and survival assessment. Tumor response was evaluated through tumor growth delay.Within each tested total dose using a constant MDR (>100 Gy/s), increasing DPP led to an increase in sparing (an increase in the number of regenerating crypts), with a more prominent effect seen at 12- and 14-Gy TAI. Interestingly, at DPPs of >4 Gy, a similar level of crypt sparing was demonstrated irrespective of the MDR used (from 0.3 to 1440 Gy/s). At a fixed high-DPP of 4.7 Gy, survival was equivalently improved relative to CONV irrespective of MDR. However, at a lower DPP of 0.93 Gy, an MDR of 104 Gy/s produced a greater survival effect compared with 0.3 Gy/s. We also confirmed that high-DPP, regardless of MDR, produced the same magnitude of tumor growth delay relative to CONV using a clinically relevant melanoma mouse model.This study demonstrates the strong influence that the beam parameter settings have on the magnitude of the FLASH effect. Both high-DPP and ultra-high-dose-rate appeared independently sufficient to produce FLASH sparing of gastrointestinal toxicity while isoeffective tumor response was maintained across all conditions.