The clinical prospect of FLASH radiotherapy

FLASH radiotherapy (FLASH-RT) is a new strategy for tumor treatment with an ultra-high dose rate of more than 40 ​Gy/s. Compared with conventional radiotherapy (CONV-RT), FLASH-RT has no different inhibitory effects on tumors but less damage to normal tissues, which is called the “spare” effect. The “spare” effect triggers our exploration of the great prospect of subverting conventional radiotherapy and its intricate mechanisms. Mitochondrial homeostasis, the immune microenvironment, or DNA integrity may potentially represent the primary breakthrough direction in understanding the mechanisms. Concurrently, it is imperative to advance timely clinical translation efforts. Clinical trials of FLASH-RT have progressed to Phase II in both the United States and Switzerland, with current findings suggesting that FLASH-RT achieves comparable efficacy to CONV-RT while mitigating side effects in select cancer cell types. While summarizing the existing FLASH experiments, this paper emphasizes the significance of clinical transformation and the challenges that will be faced and proposes possible solutions.