FLASH Radiotherapy in Lung Cancer: Translational Mechanisms, Preclinical Evidence, and Barriers

This narrative review aims to compile the preclinical and translational information about FLASH radiotherapy (FLASH-RT) as a lung cancer therapy. Experimental studies on animal and ex vivo human models have shown that FLASH-RT reduces lung fibrosis and inflammation while maintaining tumor control. The "FLASH effect" is most likely brought on by immunological remodeling, reactive oxygen species (ROS) control, and brief oxygen deprivation. Proton pencil beam scanning (PBS), Bragg peak modulation, and adaptive planning are some of the innovative techniques that have contributed to improvements in high-dose-rate delivery accuracy. When it comes to real-time dosimetry, mobility management, and the standardization of dose-rate data, however, there are still hurdles to encounter. It is necessary to do more research that will include several disciplines, including biology, physics, and clinical innovation, to facilitate safe clinical translation. This review seeks to elucidate existing issues, identify information deficiencies, and inform future research and clinical trial design for FLASH-RT-based lung cancer treatments.