Online adaptive radiotherapy: Clinical utility, challenges and perspectives.

Online adaptive radiotherapy (oART) represents a major evolution in radiation oncology, enabling daily plan adaptation to account for anatomical variations during treatment. This review synthesizes current evidence on its clinical utility, implementation challenges, and future directions. A comprehensive PubMed search (2014-June 2025) identified studies reporting dosimetric and clinical outcomes for oART across tumor sites. Delivered via magnetic resonance- or computed tomography-guided systems, oART consistently improved target coverage while reducing exposure to organs at risk across multiple cancer types. Emerging clinical evidence demonstrates tangible benefits, including enhanced gastrointestinal tolerance in pancreatic stereotactic radiotherapy, improved genitourinary outcomes in prostate cancer, and encouraging early results in head and neck or thoracic tumors. However, widespread adoption remains constrained by prolonged treatment times, workflow complexity, and higher resource demands. Artificial intelligence-based tools for autosegmentation and plan optimization have the potential to enhance efficiency, though clinical oversight remains essential. Training of radiation therapists is essential to streamline workflows. Ongoing phase II-III trials aim to validate the clinical utility and cost-effectiveness of oART. Integration of radiomics, multi-omics, and other biological predictors may further refine patient selection and personalize adaptive strategies. In conclusion, oART enables precision radiotherapy tailored to daily anatomy. While dosimetric advantages are well established, large-scale prospective trials are urgently needed to confirm survival and toxicity benefits and guide optimal clinical integration.