Ultrahigh dose rate, FLASH radiotherapy has emerged as one of the most promising innovations over the past decade in the field of radiation oncology, with the potential to eradicate radiation resistant primary tumors and improve the therapeutic outcome for cancer patients. FLASH is based on delivering radiation doses at ultrahigh dose rates (UHDR; $>40\mathrm{Gy}/\mathrm{s}$), more than 1000 times faster than irradiation at conventional dose rates (CONV). The experimental evidence demonstrating the differential effect of dose rate modulation on tumors and normal tissue is reviewed. Preclinical data consistently show that the antitumor efficacy of cytotoxic doses is not dependent on dose rate, but in normal tissues UHDR significantly reduces normal tissue toxicities compared to CONV, as observed in vivo. These observations define the FLASH effect. The FLASH effect has been reported to occur when using single or hypofractionated dose regimens in several experimental animal models (mice, rat, zebrafish, pig, and cats) and in multiple organs (lung, skin, gut, and brain) by numerous groups worldwide. Note that the FLASH effect has been demonstrated with electron, photon, and hadron (proton and heavier ion) beams. The current status and future technological development are reviewed, with an emphasis on critical beam parameters, future beam modalities, and prerequisites for safe clinical translation in terms of dosimetry, radioprotection, and treatment planning systems. Mechanistic investigations at the physicochemical and biological levels are presented, as are strategies to support and initiate clinical translation. This comprehensive review provides multidisciplinary radiation scientists with a road map of the technological, physical, chemical, biological, and clinical considerations that have made FLASH topical. These considerations are presented with a realistic and practical backdrop of the limitations and challenges that lie ahead.

中文翻译：

---

FLASH：物理、化学、生物学和癌症医学的新交叉点


超高剂量率FLASH放射治疗已成为过去十年放射肿瘤学领域最有前途的创新之一，有可能根除放射抗性原发肿瘤并改善癌症患者的治疗结果。 FLASH 基于以超高剂量率提供辐射剂量（UHDR； $>40\mathrm{Gy}/\mathrm{s}$ ），比常规剂量率 (CONV) 照射快 1000 倍以上。回顾了证明剂量率调节对肿瘤和正常组织的不同影响的实验证据。临床前数据一致表明，细胞毒性剂量的抗肿瘤功效不依赖于剂量率，但在正常组织中，与 CONV 相比，UHDR 显着降低了正常组织毒性，如体内观察到的。这些观察结果定义了 FLASH 效果。据报道，全球许多团体在几种实验动物模型（小鼠、大鼠、斑马鱼、猪和猫）和多个器官（肺、皮肤、肠道和大脑）中使用单次或大分割剂量方案时，会出现 FLASH 效应。请注意，闪光效应已通过电子、光子和强子（质子和重离子）束得到证实。回顾了当前的现状和未来的技术发展，重点是关键的射束参数、未来的射束模式以及剂量测定、辐射防护和治疗计划系统方面安全临床转化的先决条件。提出了物理化学和生物学水平的机制研究，以及支持和启动临床转化的策略。 这篇全面的综述为多学科放射科学家提供了使 FLASH 成为热门话题的技术、物理、化学、生物和临床考虑因素的路线图。这些考虑因素是在未来的限制和挑战的现实和实际背景下提出的。