Radiation Therapy in Adolescents and Young Adults (AYA): A Systematic Review of Utilization, Outcomes, Late Toxicities, and Second Malignant Neoplasms

This systematic review aims to synthesize contemporary evidence regarding the utilization and clinical impact of modern radiation therapy (RT) techniques in adolescents and young adults (AYAs; aged 15–39 years). Given the excellent long-term survival rates in this population, minimizing treatment-related late sequelae is a clinical priority. The primary objective is to evaluate how advanced RT modalities, including intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and particle therapy (proton and carbon-ion therapy), influence organ-at-risk (OAR) sparing and long-term outcomes compared to historical techniques. The review focuses on clinical effectiveness, late toxicities (defined as CTCAE ≥ grade 2), and the incidence of secondary malignant neoplasms (SMN). Expected outcomes include a comprehensive mapping of current RT utilization patterns in the AYA cohort and an assessment of the dosimetric and clinical advantages of modern techniques. The findings will provide a critical overview of the evidence base for radiation optimization and help identify gaps in long-term survivorship data, supporting the development of evidence-based guidelines for this distinct patient group.