REVIEW article
Front. Oncol.
Sec. Radiation Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1642745
FLASH-RT for Pulmonary Protection: A Comprehensive Review of Mechanisms, Technological Advances, and Clinical Translation
Provisionally accepted
- Mianyang Central Hospital, Mianyang, China
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FLASH radiotherapy (FLASH-RT), characterized by ultra-high dose rates (>40 Gy/s), has demonstrated remarkable normal tissue-sparing effects in preclinical models while maintaining tumor control. This review specifically focuses on FLASH-mediated pulmonary protection, a critical concern in thoracic oncology. We critically evaluate proposed mechanisms—including oxygen depletion, radical recombination, mitochondrial preservation, DNA integrity maintenance, metabolic modulation, and immune reprogramming—with an emphasis on the strength and limitations of current evidence across in vitro, in vivo, and emerging clinical studies. Additionally, we summarize recent technological advances enabling clinical translation, such as FLASH-compatible beam modalities, real-time dosimetry, and motion management strategies. Unlike previous reviews, we integrate these mechanisms into a unified conceptual model and provide a structured comparison of evidence quality and contradictions. This work aims to clarify current controversies, highlight knowledge gaps, and guide future research and clinical trial design for FLASH-RT–based lung protection.
Keywords: FLASH radiotherapy (FLASH-RT), Pulmonary protection, mechanisms, technological advances, clinical translation
Received: 07 Jun 2025; Accepted: 22 Aug 2025.
Copyright: © 2025 Wen, Liu, Zhang, Long, Feng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yixue Wen, Mianyang Central Hospital, Mianyang, China
Zhen Zhang, Mianyang Central Hospital, Mianyang, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.