Geirnaert Febe, Kerkhove Lisa, Montay-Gruel Pierre, Gevaert Thierry, Dufait Inès, De Ridder Mark
Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
Radiation Oncology Department, Iridium Netwerk, 2610 Antwerp, Belgium.
Cancers (Basel). 2025 Jan 3;17(1):133. doi: 10.3390/cancers17010133.
FLASH radiotherapy (FLASH RT) is an innovative modality in cancer treatment that delivers ultrahigh dose rates (UHDRs), distinguishing it from conventional radiotherapy (CRT). FLASH RT has demonstrated the potential to enhance the therapeutic window by reducing radiation-induced damage to normal tissues while maintaining tumor control, a phenomenon termed the FLASH effect. Despite promising outcomes, the precise mechanisms underlying the FLASH effect remain elusive and are a focal point of current research. This review explores the metabolic and cellular responses to FLASH RT compared to CRT, with particular focus on the differential impacts on normal and tumor tissues. Key findings suggest that FLASH RT may mitigate damage in healthy tissues via altered reactive oxygen species (ROS) dynamics, which attenuate downstream oxidative damage. Studies indicate the FLASH RT influences iron metabolism and lipid peroxidation pathways differently than CRT. Additionally, various studies indicate that FLASH RT promotes the preservation of mitochondrial integrity and function, which helps maintain apoptotic pathways in normal tissues, attenuating damage. Current knowledge of the metabolic influences following FLASH RT highlights its potential to minimize toxicity in normal tissues, while also emphasizing the need for further studies in biologically relevant, complex systems to better understand its clinical potential. By targeting distinct metabolic pathways, FLASH RT could represent a transformative advance in RT, ultimately improving the therapeutic window for cancer treatment.
闪速放疗（FLASH RT）是癌症治疗中的一种创新模式，它能提供超高剂量率（UHDRs），这使其有别于传统放疗（CRT）。闪速放疗已显示出通过减少对正常组织的辐射诱导损伤同时维持肿瘤控制来扩大治疗窗口的潜力，这一现象被称为闪速效应。尽管取得了令人鼓舞的成果，但闪速效应背后的确切机制仍然难以捉摸，是当前研究的重点。本综述探讨了与传统放疗相比，闪速放疗引起的代谢和细胞反应，特别关注其对正常组织和肿瘤组织的不同影响。主要研究结果表明，闪速放疗可能通过改变活性氧（ROS）动态来减轻健康组织的损伤，从而减弱下游的氧化损伤。研究表明，闪速放疗对铁代谢和脂质过氧化途径的影响与传统放疗不同。此外，多项研究表明，闪速放疗能促进线粒体完整性和功能的维持，这有助于维持正常组织中的凋亡途径，减轻损伤。目前对闪速放疗后代谢影响的了解突出了其将正常组织毒性降至最低的潜力，同时也强调需要在生物相关的复杂系统中进行进一步研究，以更好地了解其临床潜力。通过靶向不同的代谢途径，闪速放疗可能代表放疗领域的一项变革性进展，最终改善癌症治疗的治疗窗口。
