Opportunities and Challenges in FLASH Radiotherapy: Focusing on Normal Tissue Protection Effects and Clinical Translation Bottleneck
7 affiliations
- 1Department of Oncology Guizhou Provincial People's Hospital Guiyang China
- 2Department of Biotherapy, Cancer Center West China Hospital, Sichuan University Chengdu China
- 3Institute of Fluid Physics Chinese Academy of Engineering Physics Mianyang China
- 4Department of Pain Management, Cancer Center West China Hospital, Sichuan University Chengdu China
- 5Guizhou University of Traditional Chinese Medicine Guiyang China
- 6Department of Oncology, NHC Key Laboratory of Pulmonary Immune‐Related Diseases Guizhou Provincial People's Hospital Guiyang China
- 7Sichuan Provincial Key Laboratory of Nuclear Physics and Medical Research Sichuan University Chengdu China
Abstract
FLASH radiotherapy (FLASH‐RT) has garnered significant attention for its “FLASH effect”, which selectively protects normal tissues while maintaining tumor‐killing efficacy at ultra‐high dose rates (UHDR). This technology represents a promising but still investigational therapeutic strategy in radiation oncology. Since the initial confirmation of the FLASH effect in mouse experiments in 2014, related research has rapidly advanced in key radiation physics parameters, radiation types, and biological mechanisms. However, a lack of consensus on its critical triggering conditions, tissue‐specific thresholds, and standardized parameters has hindered its transition from laboratory to clinical application. This review systematically outlines the physical triggering conditions of the FLASH effect, revealing its dependence on a multidimensional combination of parameters including dose rate, single‐fraction dose, pulse time structure, and radiation type. It also delves into the underlying multiscale biological mechanisms, encompassing radiochemical aspects such as transient oxygen depletion and free radical kinetics, cellular processes including DNA damage repair and cell death patterns, and systemic changes like immune microenvironment remodeling. It further examines three core challenges hindering FLASH‐RT's clinical implementation: technical feasibility and equipment limitations, the complexity and uncertainty of biological mechanisms, and challenges in clinical practice and standardization. This review aims to dissect current research progress and critical issues, providing guidance for advancing FLASH‐RT's clinical application.
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BibTeX
@article{he2026opportunities,
title = {{Opportunities and Challenges in FLASH Radiotherapy: Focusing on Normal Tissue Protection Effects and Clinical Translation Bottleneck}},
author = {Xuan‐Lu He and Hong‐Shuai Li and Fei Tang and Yi Zhang and Wen Yang and Ya‐Ting Lu and Jia‐Min Guo and Wen‐Jun Meng and Zhen Liu and Yu Zhang and Xing‐Chen Peng},
journal = {Cancer Medicine},
year = {2026},
month = nov,
doi = {10.1002/cam4.72392},
url = {https://doi.org/10.1002/cam4.72392},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Opportunities and Challenges in FLASH Radiotherapy: Focusing on Normal Tissue Protection Effects and Clinical Translation Bottleneck
AU - Xuan‐Lu He
AU - Hong‐Shuai Li
AU - Fei Tang
AU - Yi Zhang
AU - Wen Yang
AU - Ya‐Ting Lu
AU - Jia‐Min Guo
AU - Wen‐Jun Meng
AU - Zhen Liu
AU - Yu Zhang
AU - Xing‐Chen Peng
PY - 2026
DA - 2026/11/05
JO - Cancer Medicine
DO - 10.1002/cam4.72392
UR - https://doi.org/10.1002/cam4.72392
AB - FLASH radiotherapy (FLASH‐RT) has garnered significant attention for its “FLASH effect”, which selectively protects normal tissues while maintaining tumor‐killing efficacy at ultra‐high dose rates (UHDR). This technology represents a promising but still investigational therapeutic strategy in radiation oncology. Since the initial confirmation of the FLASH effect in mouse experiments in 2014, related research has rapidly advanced in key radiation physics parameters, radiation types, and biological mechanisms. However, a lack of consensus on its critical triggering conditions, tissue‐specific thresholds, and standardized parameters has hindered its transition from laboratory to clinical application. This review systematically outlines the physical triggering conditions of the FLASH effect, revealing its dependence on a multidimensional combination of parameters including dose rate, single‐fraction dose, pulse time structure, and radiation type. It also delves into the underlying multiscale biological mechanisms, encompassing radiochemical aspects such as transient oxygen depletion and free radical kinetics, cellular processes including DNA damage repair and cell death patterns, and systemic changes like immune microenvironment remodeling. It further examines three core challenges hindering FLASH‐RT's clinical implementation: technical feasibility and equipment limitations, the complexity and uncertainty of biological mechanisms, and challenges in clinical practice and standardization. This review aims to dissect current research progress and critical issues, providing guidance for advancing FLASH‐RT's clinical application.
SN - 2045-7634
ER -