Borghini Andrea, Labate Luca, Piccinini Simona, Panaino Costanza Maria Vittoria, Andreassi Maria Grazia, Gizzi Leonida Antonio
CNR Institute of Clinical Physiology, 56124 Pisa, Italy.
Intense Laser Irradiation Laboratory (ILIL), CNR Istituto Nazionale di Ottica, 56124 Pisa, Italy.
Int J Mol Sci. 2024 Feb 22;25(5):2546. doi: 10.3390/ijms25052546.
Major strides have been made in the development of FLASH radiotherapy (FLASH RT) in the last ten years, but there are still many obstacles to overcome for transfer to the clinic to become a reality. Although preclinical and first-in-human clinical evidence suggests that ultra-high dose rates (UHDRs) induce a sparing effect in normal tissue without modifying the therapeutic effect on the tumor, successful clinical translation of FLASH-RT depends on a better understanding of the biological mechanisms underpinning the sparing effect. Suitable in vitro studies are required to fully understand the radiobiological mechanisms associated with UHDRs. From a technical point of view, it is also crucial to develop optimal technologies in terms of beam irradiation parameters for producing FLASH conditions. This review provides an overview of the research progress of FLASH RT and discusses the potential challenges to be faced before its clinical application. We critically summarize the preclinical evidence and in vitro studies on DNA damage following UHDR irradiation. We also highlight the ongoing developments of technologies for delivering FLASH-compliant beams, with a focus on laser-driven plasma accelerators suitable for performing basic radiobiological research on the UHDR effects.
在过去十年中，闪疗（FLASH放疗，FLASH RT）取得了重大进展，但要转移至临床成为现实仍有许多障碍需要克服。尽管临床前和首次人体临床证据表明，超高剂量率（UHDRs）可在不改变对肿瘤治疗效果的情况下对正常组织产生保护作用，但FLASH-RT的成功临床转化依赖于对支撑该保护作用的生物学机制有更深入的了解。需要进行合适的体外研究以全面了解与UHDRs相关的放射生物学机制。从技术角度来看，在产生FLASH条件的束流照射参数方面开发最佳技术也至关重要。本综述概述了FLASH RT的研究进展，并讨论了其临床应用前所面临的潜在挑战。我们批判性地总结了关于UHDR照射后DNA损伤的临床前证据和体外研究。我们还强调了适用于产生符合FLASH条件束流的技术的持续发展，重点关注适用于对UHDR效应进行基础放射生物学研究的激光驱动等离子体加速器。
