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<p>Ultra-high dose rate (FLASH) radiotherapy is a novel modality delivering dose rates several orders of magnitude higher than conventional dose rate (CONV) radiotherapy. FLASH radiotherapy has been shown to significantly reduce the damaging effects on normal tissues while achieving similar tumor control, a phenomenon referred to as the FLASH effect. Radiation-induced lung injury (RILI) represents a prevalent complication in thoracic tumor radiotherapy, significantly compromising treatment outcomes and patient quality of life. Emerging preclinical evidence consistently demonstrates that FLASH radiotherapy significantly attenuates radiation-induced lung injury compared to CONV radiotherapy. The observed radioprotection primarily manifests in structural preservation of alveolar epithelium, pulmonary vasculature, and bronchial networks, concomitant with substantial reductions in both radiation pneumonitis and subsequent pulmonary fibrosis. Current evidence suggests that RILI pathogenesis involves multiple mechanisms, including DNA damage and repair, reactive oxygen species (ROS) and oxidative stress, inflammation, and immune response. These mechanistic insights provide a crucial foundation for investigating the radiobiological basis of the FLASH effect. Our review summarizes the preclinical studies of FLASH radiotherapy in mitigating lung injury. Furthermore, it explores the potential mechanisms underlying the FLASH effect from the perspective of the biological mechanism of RILI, aiming to provide a reference and direction for the clinical translation of FLASH radiotherapy.</p>

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Effects and potential mechanisms of the ultra-high dose rate radiotherapy on lung injury: a review

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月4日

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  • Zhipeng Li,
  • Xingdong Guo,
  • Xiao Lei,
  • Yuan Wang,
  • Qiduo He,
  • Pei Zhang,
  • Lehui Du,
  • Baolin Qu

摘要

Ultra-high dose rate (FLASH) radiotherapy is a novel modality delivering dose rates several orders of magnitude higher than conventional dose rate (CONV) radiotherapy. FLASH radiotherapy has been shown to significantly reduce the damaging effects on normal tissues while achieving similar tumor control, a phenomenon referred to as the FLASH effect. Radiation-induced lung injury (RILI) represents a prevalent complication in thoracic tumor radiotherapy, significantly compromising treatment outcomes and patient quality of life. Emerging preclinical evidence consistently demonstrates that FLASH radiotherapy significantly attenuates radiation-induced lung injury compared to CONV radiotherapy. The observed radioprotection primarily manifests in structural preservation of alveolar epithelium, pulmonary vasculature, and bronchial networks, concomitant with substantial reductions in both radiation pneumonitis and subsequent pulmonary fibrosis. Current evidence suggests that RILI pathogenesis involves multiple mechanisms, including DNA damage and repair, reactive oxygen species (ROS) and oxidative stress, inflammation, and immune response. These mechanistic insights provide a crucial foundation for investigating the radiobiological basis of the FLASH effect. Our review summarizes the preclinical studies of FLASH radiotherapy in mitigating lung injury. Furthermore, it explores the potential mechanisms underlying the FLASH effect from the perspective of the biological mechanism of RILI, aiming to provide a reference and direction for the clinical translation of FLASH radiotherapy.