The radiobiological mechanism of FLASH radiotherapy

The core goal of radiotherapy is to eradicate tumors and minimize toxicity to normal tissues to the greatest extent. FLASH radiotherapy (Flash-RT), as a cutting-edge technology in the field of tumor radiotherapy, is regarded as an important direction to break through the limitations of the traditional treatment window. Recent preclinical studies have shown that FLASH-RT significantly expands the therapeutic window of radiotherapy through its unique characteristics of extremely short irradiation time (<0.1 seconds) and ultra-high dose rate (>40 Gy/s) - it can not only enhance the anti-tumor effect and maintain the tumor control probability (TCP) by increasing the dose, It can also reduce the probability of normal tissue complications (NTCP). Furthermore, the significant reduction in its treatment time can avoid the positioning errors caused by organ movement and expand the group of treatable patients. However, due to the extremely short action time of FLASH-RT, the current mechanism research on its biological effects is mostly based on indirect evidence, and some mechanisms are not yet clear and there are contradictory conclusions. This article systematically reviews the radiobiological mechanism of FLASH-RT and, in combination with the limitations of existing research, proposes the key directions for future research.