Mechanisms of radiation-induced skin injury and implications for future clinical trials

Purpose: To summarize current knowledge regarding mechanisms of radiation-induced skin injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Although skin is not a radiation dose-limiting tissue, injury to skin poses substantial morbidity risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. In the continuum of radiation-induced skin injury, late effects are most severe being characterized by sub-cutaneous fibrosis and morbidity. The principal pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Emerging concepts of radiation- induced skin injury suggest that the recovery of stromal stem cells and tissue repair remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure.Conclusions: As pathways underlying the cellular and molecular mechanisms of radiation-induced skin injury are becoming better understood, novel approaches are being developed for mitigating or treating the associated pathogenesis.