Radiotherapy-Induced Side Effects: Epidemiology, Pathogenesis, Prevention and Treatments

The widespread application of radiotherapy for malignancies underscores the urgent clinical challenge of radiation-induced multiorgan injury, which severely impacts patient prognosis and quality of life. The heart, skin, lungs, intestines, hematopoietic system, oral, kidney, and brain are the most frequently affected sites, each following distinct and complex injury trajectories. Despite growing research into these organ-specific injuries, a substantial translational gap remains between mechanistic insights and effective therapeutic interventions. This review systematically delineates the unique epidemiological and pathological processes in these eight critical systems. It then critically evaluates current clinical management alongside emerging therapeutic strategies, including advanced radioprotectors, mitigators, antifibrotic agents, and innovative stem cell therapies. Central to our analysis is the synthesis of these findings into a comprehensive view of the complex interactive networks and functional imbalances driven by aberrant intercellular communication within damaged tissues. By offering a systematic analysis of mechanism-network-targeted therapeutics, this review establishes a critical framework to guide the future development of more effective, integrated, and personalized patient care strategies in radiation oncology.