FLASH radiotherapy: technical advances, evidence of the FLASH effect and mechanistic insights

Cancer is one of the leading causes of death worldwide, responsible for nearly 10 million deaths in 2020, with approximately 50% of patients receiving radiation therapy as part of their treatment (Baskaret al2012). Preclinical investigations studies have shown that FLASH radiotherapy (FLASH-RT), delivering radiation in ultra-high dose rates (UHDR), preserves healthy tissue integrity and reduces toxicity, all while maintaining an effective tumor response compared to conventional radiotherapy (CONV-RT), the combined biological benefit was termed as FLASH effect. This article comprehensively surveys pertinent research conducted within FLASH-RT, explores the facilities used in this realm, delves into hypothesized mechanism perspectives, and addresses the challenges to trigger the FLASH effect. In addition, we discuss the potential prospects of FLASH-RT and examine the obstacles that require resolution before its clinical implementation can become a reality.