Advances in FLASH radiation therapy: A review on biological foundations and clinical prospects

• FLASH-RT leverages ultra-high dose rates to achieve a differential radiobiological effect, significantly sparing normal tissues while maintaining potent tumor cell killing. • Significant advancements are underway in developing specialized equipment, precise dosimetry systems, and real-time imaging techniques to enable safe clinical delivery. • Current research prioritizes understanding the underlying biological mechanisms, optimizing treatment parameters, and rigorously addressing safety concerns and efficacy uncertainties through clinical trials. • Despite existing technical and biological hurdles, FLASH-RT holds transformative potential to improve radiotherapy outcomes across diverse cancer types and warrants continued multidisciplinary development for clinical translation. This paper provides a comprehensive review of the fundamental theories, clinical practices, technological advancements, current status, and future prospects of FLASH radiation therapy (FLASH-RT). As an emerging technique, FLASH-RT offers the potential to enhance therapeutic efficacy while minimizing damage to healthy tissues. We elaborate on the physical principles of the “FLASH effect” in radiation biology and its dose-distribution characteristics, describe clinical applications in tumor treatment, and evaluate protective effects on normal tissues. Furthermore, the review discusses technical advancements in equipment, dosimetry, and imaging, while analyzing current research hotspots and technical bottlenecks. We also examine pathological mechanisms, future applications, and prevailing controversies regarding safety, efficacy uncertainty, and ethics. This comprehensive discussion provides a valuable reference for deepening the understanding of FLASH-RT’s translational journey.