First demonstration of the FLASH effect with ultrahigh dose-rate high-energy X-rays

Gao, Feng; Yang, Yiwei; Zhu, Hongyu; Wang, JianXin; Xiao, Dexin; Zhou, Zheng; Dai, Tangzhi; Zhang, Yu; Feng, Gang; Li, Jie; Lin, Binwei; Xie, Gang; Ke, Qi; Zhou, Kui; Li, Peng; Shen, Xuming; Wang, Hanbin; Yan, Longgang; Lao, Chenglong; Shan, Lijun; Li, Ming; Lu, Yanhua; Chen, Menxue; Feng, Song; Zhao, Jianheng; Wu, Dai; Du, Xiaobo

Ultrahigh dose-rate (FLASH) radiotherapy has attracted immense attention because of its tumor control efficiency and healthy tissue protection during preclinical experiments with electrons, kilo-voltage X-rays, and protons. Using high-energy X-rays (HEXs) in FLASH is advantageous owing to its deep penetration, small divergence, and cost-effectiveness. This is the first report on the implementation of HEXs with FLASH (HEX-FLASH) and its corresponding application in vivo. With a high-current and high-energy superconducting linear accelerator, FLASH with a good dose rate and high penetration was achieved. Breast cancers artificially induced in BAL b/c mice were efficiently controlled, and normal tissues surrounding the thorax/abdomen in C57BL/6 mice were protected from radiation with HEX-FLASH. Theoretical analyses of cellular responses following HEX-FLASH irradiation were performed to interpret the experimental results and design further experiments. Thus, this study highlights the generation of HEX-FLASH for the first time and its potential in future clinical applications.