Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania..
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Semin Radiat Oncol. 2024 Apr;34(2):218-228. doi: 10.1016/j.semradonc.2024.02.001.
FLASH is an emerging treatment paradigm in radiotherapy (RT) that utilizes ultra-high dose rates (UHDR; >40 Gy)/s) of radiation delivery. Developing advances in technology support the delivery of UHDR using electron and proton systems, as well as some ion beam units (eg, carbon ions), while methods to achieve UHDR with photons are under investigation. The major advantage of FLASH RT is its ability to increase the therapeutic index for RT by shifting the dose response curve for normal tissue toxicity to higher doses. Numerous preclinical studies have been conducted to date on FLASH RT for murine sarcomas, alongside the investigation of its effects on relevant normal tissues of skin, muscle, and bone. The tumor control achieved by FLASH RT of sarcoma models is indistinguishable from that attained by treatment with standard RT to the same total dose. FLASH's high dose rates are able to mitigate the severity or incidence of RT side effects on normal tissues as evaluated by endpoints ranging from functional sparing to histological damage. Large animal studies and clinical trials of canine patients show evidence of skin sparing by FLASH vs. standard RT, but also caution against delivery of high single doses with FLASH that exceed those safely applied with standard RT. Also, a human clinical trial has shown that FLASH RT can be delivered safely to bone metastasis. Thus, data to date support continued investigations of clinical translation of FLASH RT for the treatment of patients with sarcoma. Toward this purpose, hypofractionated irradiation schemes are being investigated for FLASH effects on sarcoma and relevant normal tissues.
FLASH 是放射治疗（RT）中的一种新兴治疗模式，利用超高剂量率（UHDR；>40 Gy/s）的辐射传递。技术的发展进步支持使用电子和质子系统以及一些离子束单位（如碳离子）来传递 UHDR，同时也在研究如何使用光子来实现 UHDR。FLASH RT 的主要优势在于，它能够通过将正常组织毒性的剂量反应曲线转移到更高的剂量，从而提高 RT 的治疗指数。迄今为止，已经对FLASH RT 治疗鼠肉瘤进行了大量的临床前研究，同时还研究了其对皮肤、肌肉和骨骼等相关正常组织的影响。FLASH RT 治疗肉瘤模型的肿瘤控制效果与相同总剂量标准 RT 治疗的效果相同。FLASH 的高剂量率能够减轻正常组织的 RT 副作用的严重程度或发生率，通过从功能保留到组织学损伤的各种终点来评估。大型动物研究和犬科患者的临床试验证据表明，FLASH 与标准 RT 相比可以使皮肤免受照射，但也警告不要使用超过标准 RT 安全应用剂量的高单次剂量进行 FLASH 传递。此外，一项人体临床试验表明，FLASH RT 可安全地用于骨转移。因此，迄今为止的数据支持继续研究 FLASH RT 治疗肉瘤患者的临床转化。为此，正在研究FLASH 对肉瘤和相关正常组织的超分割照射方案。
