Radiation therapy in adolescents and young adults (AYA): contemporary evidence on utilization, outcomes, late toxicities, and second malignant neoplasms - A comprehensive systematic review and synthesis
Abstract
Adolescent and young adult (AYA; 15-39 years) cancer survivors face decades of potential life-years, making radiotherapy (RT) modality and technique selection central determinants of long-term health. A PRISMA 2020-reported systematic review was performed using PubMed, Web of Science, and the Cochrane Library (January 2026). Data were synthesised qualitatively using a Synthesis Without Meta-analysis (SWiM) approach. The primary synthesis focused on RT utilization and late outcomes including late toxicity, survivorship morbidity, patient-reported outcomes, and secondary malignant neoplasms (SMN), and model-based estimates of SMN risk where available. Thirty-five primary studies were included in the qualitative synthesis. For tumours of the central nervous system (CNS) and skull base, proton beam therapy (PBT) showed high local control; anterior pituitary dysfunction was frequent (36.3 %), requiring anatomical interpretation. In AYA breast cancer, volumetric modulated arc therapy with a simultaneous integrated boost (VMAT-SIB) achieved a favourable early safety profile, with no reported cardiovascular events at a median follow-up of 86.5 months. In testicular seminoma, PBT significantly reduced acute gastrointestinal (GI) toxicity (0 % vs 29.5 % grade 1-2 diarrhoea, p = 0.039) and was associated with a 50-60 % lower model-estimated SMN risk. Modern RT techniques appear to reduce the burden of late effects in AYAs across the most frequently studied tumour sites. However,…
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