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不同分割次数和剂量率的超高剂量率放疗对小鼠急性和慢性肺损伤的影响。

Effects of ultra-high dose rate radiotherapy with different fractions and dose rate on acute and chronic lung injury in mice.

作者信息

Gao Feng, Lin Binwei, Yang Yiwei, Xiao Dexin, Zhou Zheng, Zhang Yu, Feng Gang, Li Jie, Wu Dai, Du Xiaobo, Shi Qiuling

机构信息

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China.

Departmant of Oncology, Nuclear Medicine Laboratory of Mianyang Central Hospital, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China.

出版信息

Heliyon. 2024 Nov 14;10(22):e40298. doi: 10.1016/j.heliyon.2024.e40298. eCollection 2024 Nov 30.

DOI:10.1016/j.heliyon.2024.e40298
PMID:39641017
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11617221/
Abstract

Ultra-high dose rate radiotherapy (FLASH radiation) can naturally render normal tissues around the tumor tissue resistant to radiotherapy. In contrast, the tumor tissue remains sensitive to radiation under the same conditions. However, the effects of different fractions and dose rates on FLASH radiation remain unclear. This study aimed to determine the optimal dose rate and fraction of FLASH radiation for thoracic radiotherapy. Female Balb/c mice aged 6-8 weeks were irradiated with different dose rates (100 Gy/s or 250 Gy/s) and fractions (1, 2, or 4). Survival was observed in mice receiving 30Gy, with lung tissue examined for acute radiation damage 48 h post-radiation. Late radiation pneumonia and survival rates were monitored in mice irradiated with 20 Gy. The median overall survival (OS) was not reached on the 95th day for mice irradiated with 250 Gy/s FLASH radiation, while it was 89.5 days for those irradiated with 100 Gy/s (P = 0.0436). Mice irradiated with 30 Gy/2 Fr and 250 Gy/s FLASH had shorter median OS than those with 30 Gy/1F (P = 0.0132). However, there was no significant difference in OS between mice irradiated with 30 Gy/2 F and 30 Gy/4 F. Survival curves for mice receiving 20 Gy showed no significant difference in toxicity between different dose rates and fractions. FLASH radiation at 250 Gy/s reduced the incidence of acute radiation pneumonitis in mice compared to 100 Gy/s. Different fractions of irradiation influenced survival in mice, but they were only observed in acute radiation reactions and not chronic radiation reactions. Among the tested fraction methods, fraction 2 had the worst impact on the survival of mice, while fractions 1 and 4 showed similar effects and improved survival compared to fraction 2.

摘要

超高剂量率放疗(FLASH放疗)能够使肿瘤组织周围的正常组织自然地对放疗产生抗性。相比之下,在相同条件下肿瘤组织对辐射仍保持敏感。然而,不同分次剂量和剂量率对FLASH放疗的影响仍不清楚。本研究旨在确定胸部放疗中FLASH放疗的最佳剂量率和分次剂量。对6至8周龄的雌性Balb/c小鼠给予不同剂量率(100 Gy/s或250 Gy/s)和分次剂量(1次、2次或4次)的照射。观察接受30 Gy照射小鼠的存活情况,并在放疗后48小时检查肺组织的急性辐射损伤。对接受20 Gy照射的小鼠监测迟发性放射性肺炎和存活率。接受250 Gy/s FLASH放疗的小鼠在第95天时未达到中位总生存期(OS),而接受100 Gy/s照射的小鼠为89.5天(P = 0.0436)。接受30 Gy/2次和250 Gy/s FLASH照射的小鼠中位OS短于接受30 Gy/1次照射的小鼠(P = 0.0132)。然而,接受30 Gy/2次和30 Gy/4次照射的小鼠之间OS无显著差异。接受20 Gy照射小鼠的生存曲线显示,不同剂量率和分次剂量之间的毒性无显著差异。与100 Gy/s相比,250 Gy/s的FLASH放疗降低了小鼠急性放射性肺炎的发生率。不同分次照射影响小鼠的存活情况,但仅在急性辐射反应中观察到,而非慢性辐射反应。在测试的分次方法中,分次2对小鼠存活的影响最差,而分次1和4显示出相似的效果,且与分次2相比提高了存活率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea46/11617221/3c00f3bbf36a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea46/11617221/a67aa0e1a595/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea46/11617221/a3e1c6dddbc0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea46/11617221/3c00f3bbf36a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea46/11617221/a67aa0e1a595/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea46/11617221/a3e1c6dddbc0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea46/11617221/3c00f3bbf36a/gr3.jpg

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本文引用的文献

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"Primer shot" fractionation with an early treatment break is theoretically superior to consecutive weekday fractionation schemes for early-stage non-small cell lung cancer.“首剂”分割与早期治疗中断在理论上优于连续工作日分割方案,适用于早期非小细胞肺癌。
Radiother Oncol. 2024 Jan;190:110006. doi: 10.1016/j.radonc.2023.110006. Epub 2023 Nov 14.
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Is there still a place for radiotherapy in gastric cancer?胃癌的放射治疗是否仍有一席之地?
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Comparison of intratumor and local immune response between MV X-ray FLASH and conventional radiotherapies.
MV X射线FLASH放疗与传统放疗之间肿瘤内及局部免疫反应的比较。
Clin Transl Radiat Oncol. 2022 Nov 9;38:138-146. doi: 10.1016/j.ctro.2022.11.005. eCollection 2023 Jan.
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FLASH X-ray spares intestinal crypts from pyroptosis initiated by cGAS-STING activation upon radioimmunotherapy.FLASH 射线可避免放射性免疫治疗中 cGAS-STING 激活引发的细胞焦亡对肠隐窝造成的损伤。
Proc Natl Acad Sci U S A. 2022 Oct 25;119(43):e2208506119. doi: 10.1073/pnas.2208506119. Epub 2022 Oct 18.
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Mechanisms of FLASH effect.FLASH效应的机制。
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Med Phys. 2022 Sep;49(9):6171-6182. doi: 10.1002/mp.15844. Epub 2022 Jul 14.
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