Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark.
Med Phys. 2022 Mar;49(3):2039-2054. doi: 10.1002/mp.15276. Epub 2021 Oct 26.
We review the current status of proton FLASH experimental systems, including preclinical physical and biological results. Technological limitations on preclinical investigation of FLASH biological mechanisms and determination of clinically relevant parameters are discussed. A review of the biological data reveals no reproduced proton FLASH effect in vitro and a significant in vivo FLASH sparing effect of normal tissue toxicity observed with multiple proton FLASH irradiation systems. Importantly, multiple studies suggest little or no difference in tumor growth delay for proton FLASH when compared to conventional dose rate proton radiation. A discussion follows on future areas of development with a focus on the determination of the optimal parameters for maximizing the therapeutic ratio between tumor and normal tissue response and ultimately clinical translation of proton FLASH radiation.
我们回顾了质子 FLASH 实验系统的现状,包括临床前的物理和生物学结果。讨论了临床相关参数的确定和 FLASH 生物学机制的临床前研究的技术限制。对生物学数据的回顾表明,体外没有复制出质子 FLASH 效应,并且在多个质子 FLASH 照射系统中观察到正常组织毒性的明显体内 FLASH 保护效应。重要的是,多项研究表明,与常规剂量率质子照射相比,质子 FLASH 对肿瘤生长延迟的影响差异不大。随后讨论了未来的发展领域,重点是确定最佳参数,以最大限度地提高肿瘤和正常组织反应的治疗比率,并最终实现质子 FLASH 辐射的临床转化。
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