Fractionation increasingly reduces FLASH sparing for acute murine skin damage.

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology Pub Date : 2025-10-17 DOI:10.1016/j.radonc.2025.111209

Line Kristensen, Sky Rohrer, Jacob Graversen Johansen, Lone Hoffmann, Lars Hjorth Præstegaard, Anna Holtz Hansen, Per Rugaard Poulsen, Brita Singers Sørensen

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引用次数: 0

Abstract

Background and purpose: Preclinical studies report a favourable normal tissue-sparing FLASH effect. Most studies report single-fraction irradiations. The interplay between fractionation and FLASH sparing is highly relevant for clinical translation but is scarce in the literature. This study compared the tissue-sparing effect of FLASH on acute skin toxicity with single-fraction, four-fraction and eight-fraction schemes.

Materials and methods: Acute skin toxicity after conventional dose rate (CONV, 0.16 Gy/s) and FLASH (mean ± sd 251 ± 12 Gy/s) irradiation was assessed in female CDF1 mice. The right hindleg of unanaesthetised mice was irradiated using a single dose (1 fraction), one daily dose for four consecutive days (4 fractions) or two daily doses with a 6-hour interval for four consecutive days (8 fractions). The study had 4-12 mice per dose group. The total dose per group ranged from 24.5 to 89.9 Gy. A FLASH-enabled accelerator (TrueBeam, Varian) delivered irradiation with a 16 MeV electron beam. Acute skin toxicity was quantified daily from 9 to 28 days post-treatment.

Results: Single-fraction irradiation had a tissue-sparing FLASH effect, which was halved for four fractions and markedly reduced for eight fractions. The dose modification ratio was 1.41 for a single fraction, 1.18 for four fractions, and nonsignificantly 1.05 for eight fractions.

Conclusion: Fractionation increasingly reduced the acute skin-sparing effect seen in single-fraction FLASH studies. However, a tissue-sparing effect of 18 % was still present at four fractions, while eight fractions provided a nonsignificant 5 % FLASH skin-sparing. Clinical implementation of FLASH may work best in highly hypofractionated settings.

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分馏法逐渐减少急性小鼠皮肤损伤的FLASH保留。

背景和目的：临床前研究报告了良好的保留正常组织的FLASH效果。大多数研究报告的是单组分辐照。分离和FLASH保留之间的相互作用与临床翻译高度相关，但在文献中很少。本研究比较了单组分、四组分和八组分三种方案对FLASH急性皮肤毒性的组织保护作用。材料与方法：对雌性CDF1小鼠进行常规剂量率（CONV, 0.16 Gy/s）和FLASH（平均 ± sd 251 ± 12 Gy/s）照射后的急性皮肤毒性评价。未麻醉小鼠右后腿采用单次剂量（1份）、每日一次剂量连续4天（4份）或每日两次剂量间隔6小时连续4天（8份）照射。每剂量组4-12只小鼠。每组总剂量为24.5 ~ 89.9 Gy。一个flash加速器（TrueBeam, Varian）提供16 MeV的电子束辐照。在治疗后9 ~ 28 d每天定量测定急性皮肤毒性。结果：单组分辐照具有组织保护的FLASH效应，4组分的效果减半，8组分的效果显著降低。单组分的剂量修饰比为1.41,4组分的剂量修饰比为1.18,8组分的剂量修饰比为1.05。结论：在单组分FLASH研究中，分离逐渐降低了急性皮肤保留效果。然而，在4个组分中仍然存在18 %的组织保护效果，而8个组分提供了不显著的5 %的FLASH皮肤保护。临床应用FLASH可能在高度低分割的情况下效果最好。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Radiotherapy and Oncology 医学-核医学

CiteScore

10.30

自引率

10.50%

发文量

2445

审稿时长

45 days

期刊介绍： Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to radiation oncology. This includes: clinical radiotherapy, combined modality treatment, translational studies, epidemiological outcomes, imaging, dosimetry, and radiation therapy planning, experimental work in radiobiology, chemobiology, hyperthermia and tumour biology, as well as data science in radiation oncology and physics aspects relevant to oncology.Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are also published.