Sparing effects of FLASH irradiation in patient-derived lung tissue

作者：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, G. Créhange, Charles Fouillade · 发表于：Radiotherapy and Oncology · 年份：2025 · DOI：10.1016/j.radonc.2025.111126 · 被引用次数：8 · 研究领域：Effects of Radiation Exposure、Radiation Therapy and Dosimetry、Hydrogen's biological and therapeutic effects

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,...