FLASH radiotherapy (FLASH-RT) is a new modality of radiotherapy that delivers doses with ultra-high dose rates. The FLASH effect was defined as the ability of FLASH-RT to suppress tumor growth while sparing normal tissues. Although the FLASH effect has been proven to be valid in various models by different modalities of irradiation and clinical trials of FLASH-RT have achieved promising initial success, the exact underlying mechanism is still unclear. This article summarizes mainstream hypotheses of the FLASH effect at physicochemical and biological levels, including oxygen depletion and free radical reactions, nuclear and mitochondria damage, as well as immune response. These hypotheses contribute reasonable explanations to the FLASH effect and are interconnected according to the chronological order of the organism's response to ionizing radiation. By collating the existing consensus, evidence and hypotheses, this article provides a comprehensive overview of potential mechanisms of the FLASH effect and practical guidance for future investigation in the field of FLASH-RT.
FLASH放疗（FLASH-RT）是一种以超高剂量率实施照射的新型放射治疗模式。FLASH效应是指FLASH-RT在抑制肿瘤生长的同时能够保护正常组织的能力。尽管通过不同照射模式已在多种模型中证实FLASH效应有效，且FLASH-RT的临床试验已取得良好的初步成果，但其确切作用机制尚不明确。本文从物理化学与生物学层面总结了关于FLASH效应的主流假说，包括氧耗竭与自由基反应、细胞核与线粒体损伤以及免疫应答等。这些假说为FLASH效应提供了合理解释，并依据生物体对电离辐射响应的时间顺序相互关联。通过对现有共识、证据及假说的系统性梳理，本文全面综述了FLASH效应的潜在机制，并为该领域的后续研究提供了实践指导。
Current views on mechanisms of the FLASH effect in cancer radiotherapy
肿瘤(癌症)患者之家