FLASH radiotherapy effects: From physicochemical foundations to preclinical models -- a review

The ultimate goal pursued in the field of oncology therapy is to maximize the control of lesions while reducing normal tissue damage. FLASH radiotherapy (FLASH-RT) is a new radiotherapy technology mainly characterized by ultra-high dose rate irradiation (>40 Gy/s). In many preclinical studies, this technology has been proven to be able toprotect the surrounding normal tissues while controlling the tumor, and is therefore considered a promising technology that may improve the therapeutic index in radiation oncology. Although current in vivo and in vitro evidence has shown that FLASH-RT has potential protective effects on normal tissues without changing the therapeutic effect on tumors, the potential molecular and cellular mechanisms of the FLASH effect still need to be further clarified. At present, most of the biological mechanisms of the FLASH effect are based on various hypotheses (such as oxygen depletion hypothesis, reactive oxygen species hypothesis, immune response hypothesis, etc.). Based on this, this paper systematically reviews the research progress of the FLASH-RT effect from physical-chemical basis to preclinical models. At the biological level, the limitations of its clinical application are that existing preclinical studies are still not systematic and in-depth enough, and no consensus on the mechanism has been formed; at the technical level, it is crucial to develop FLASH production conditions that optimize beam irradiation parameters, but the current optimal parameter window is uncertain. In conclusion, the aim of this study is to provide a reference for more scholars to understand, pay attention to and study FLASH-RT, promote the research of FLASH-RT related equipment technology, biological basis and clinical application, add new tools to the field of cancer treatment, and better serve society and benefit mankind.