Sparing effects of FLASH irradiation in patient-derived lung tissue

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology Pub Date : 2025-09-06 DOI:10.1016/j.radonc.2025.111126

Maxime Dubail , Chloé Lafouasse , Sophie Heinrich , Vincent Favaudon , Arturo Londoño-Vallejo , Marie Dutreix , Delphine Colin , Jean-François Côté , Jérôme Didier , Christelle Pouliquen , Abdelali Benali , Pierre Verrelle , Marine Lefèvre , Nicolas Girard , Agathe Seguin-Givelet , Gilles Créhange , Charles Fouillade

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引用次数: 0

Abstract

Background and purpose

Radiation toxicities, such as pneumonitis and fibrosis, are major limitations affecting patients’ quality of life. Developed a decade ago, FLASH radiotherapy is an innovative method that, by delivering radiation at ultrafast dose rate, reduces radiation toxicities on healthy tissue while preserving the anti-tumoral effect of radiotherapy. This so-called FLASH effect has been described in different preclinical models but has not been observed in human tissue. This study aims to determine if FLASH irradiation can induce a sparing effect on human healthy lung tissue.

Materials and methods

To address this question, precision-cut lung slices (Hu-PCLS) were prepared from healthy lung samples collected from 19 lung cancer patients undergoing lobectomy. These Hu-PCLS were irradiated ex vivo at a dose of 9 Gy using the ElectronFLASH (SIT) device operated either in conventional or FLASH mode. We monitored cell division for each patient and performed RNAseq analysis to uncover some mechanistic insights.

Results

Analysis of cell division 24 h after treatment with conventional or ultra-high dose rate showed a higher proportion of dividing cells in Hu-PCLS after FLASH irradiation. Consistently, RNAseq analysis from irradiated lung samples confirmed an attenuated cell cycle checkpoint inhibition, p53 pro-apoptotic genes, DNA damage, and antioxidant pathways after ultra-high dose rate compared to conventional treatment.

Conclusion

Altogether, this study shows that, using freshly isolated patient-derived lung samples, cell proliferation can serve as an early marker of the normal lung response to FLASH irradiation. These findings hold great promises for future applications of FLASH radiotherapy in the clinic.

查看原文本刊更多论文

闪光照射对患者源性肺组织的保护作用。

背景和目的：辐射毒性，如肺炎和纤维化，是影响患者生活质量的主要限制。十年前开发的FLASH放射治疗是一种创新方法，通过以超快剂量率提供辐射，减少对健康组织的辐射毒性，同时保留放射治疗的抗肿瘤作用。这种所谓的FLASH效应已经在不同的临床前模型中描述过，但尚未在人体组织中观察到。本研究旨在确定FLASH辐照是否能对人体健康肺组织产生保护作用。材料和方法：为了解决这一问题，我们从19例接受肺叶切除术的肺癌患者的健康肺样本中制备了精确切割肺片（Hu-PCLS）。这些Hu-PCLS在体外以9 Gy的剂量照射，使用在传统或FLASH模式下操作的ElectronFLASH （SIT）装置。我们监测了每个患者的细胞分裂，并进行了RNAseq分析，以揭示一些机制。结果：常规或超高剂量率照射后24 h细胞分裂分析显示，FLASH照射后Hu-PCLS细胞分裂比例更高。与常规治疗相比，来自辐照肺样本的RNAseq分析一致证实，超高剂量率后，细胞周期检查点抑制、p53促凋亡基因、DNA损伤和抗氧化途径减弱。结论：总之，本研究表明，使用新鲜分离的患者来源的肺样本，细胞增殖可以作为肺部对FLASH辐射正常反应的早期标志。这些发现为未来FLASH放射治疗在临床中的应用带来了巨大的希望。

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.