Jo Hye-Ju, Oh Taerim, Lee Ye-Rim, Kang Gi-Sue, Park Hye-Joon, Ahn G-One
College of Veterinary Medicine, Seoul National University, Seoul, Korea.
College of Medicine, Seoul National University, Seoul, Korea.
Brain Tumor Res Treat. 2023 Oct;11(4):223-231. doi: 10.14791/btrt.2023.0026.
FLASH radiotherapy (FLASH RT) is a technique to deliver ultra-high dose rate in a fraction of a second. Evidence from experimental animal models suggest that FLASH RT spares various normal tissues including the lung, gastrointestinal track, and brain from radiation-induced toxicity (a phenomenon known as FLASH effect), which is otherwise commonly observed with conventional dose rate RT. However, it is not simply the ultra-high dose rate alone that brings the FLASH effect. Multiple parameters such as instantaneous dose rate, pulse size, pulse repetition frequency, and the total duration of exposure all need to be carefully optimized simultaneously. Furthermore it is critical to validate FLASH effects in an experimental model system. The exact molecular mechanism responsible for this FLASH effect is not yet understood although a number of hypotheses have been proposed including oxygen depletion and less reactive oxygen species (ROS) production by FLASH RT, and enhanced ability of normal tissues to handle ROS and labile iron pool compared to tumors. In this review, we briefly overview the process of ionization event and history of radiotherapy and fractionation of ionizing radiation. We also highlight some of the latest FLASH RT reviews and results with a special interest to neurocognitive protection in rodent model with whole brain irradiation. Lastly we discuss some of the issues remain to be answered with FLASH RT including undefined molecular mechanism, lack of standardized parameters, low penetration depth for electron beam, and tumor hypoxia still being a major hurdle for local control. Nevertheless, researchers are close to having all answers to the issues that we have raised, hence we believe that advancement of FLASH RT will be made more quickly than one can anticipate.
闪速放疗（FLASH RT）是一种在几分之一秒内提供超高剂量率的技术。实验动物模型的证据表明，闪速放疗可使包括肺、胃肠道和脑在内的各种正常组织免受辐射诱导的毒性（一种称为闪速效应的现象），而在传统剂量率放疗中通常会观察到这种毒性。然而，带来闪速效应的不仅仅是超高剂量率本身。诸如瞬时剂量率、脉冲大小、脉冲重复频率和总暴露持续时间等多个参数都需要同时仔细优化。此外，在实验模型系统中验证闪速效应至关重要。尽管已经提出了许多假设，包括闪速放疗导致的氧耗竭和活性氧（ROS）产生减少，以及与肿瘤相比正常组织处理ROS和不稳定铁池的能力增强，但导致这种闪速效应的确切分子机制仍不清楚。在这篇综述中，我们简要概述了电离事件的过程以及放疗和电离辐射分次的历史。我们还重点介绍了一些最新的闪速放疗综述和结果，特别关注全脑照射的啮齿动物模型中的神经认知保护。最后，我们讨论了闪速放疗仍有待解答的一些问题，包括未明确的分子机制、缺乏标准化参数、电子束穿透深度低以及肿瘤缺氧仍然是局部控制的主要障碍。尽管如此，研究人员已接近找到我们提出的所有问题的答案，因此我们相信闪速放疗的进展将比人们预期的更快。
