Imaging Biomarkers in Radiotherapy.

Advances in medical imaging modalities such as multiparametric and functional MRI, PET, and CT/CBCT, together with complementary innovations such as radiomics, artificial intelligence (AI), adaptive radiotherapy, and theranostics, have expanded the role of imaging from anatomical guidance to biologically informed treatment planning, adaptation, and response assessment. In this review, we provide a comprehensive overview of the technical foundations of imaging biomarkers in radiotherapy (RT), spanning functional and molecular imaging techniques and data-driven analytic approaches. We synthesize current clinical evidence across major disease sites, highlighting how imaging biomarkers are being used to refine target delineation, guide dose painting and functional avoidance, predict and monitor treatment response, and support adaptive and personalized RT strategies. We also critically examine key challenges to clinical translation and implementation, including standardization and reproducibility, validation and generalizability, interpretability of AI-driven models, regulatory and ethical considerations, issues of data sharing, reimbursement, and equity. Finally, we propose a multi-stage translational roadmap to guide the development, validation, and clinical deployment of imaging biomarkers in radiotherapy. Collectively, this review underscores the central role of imaging biomarkers in advancing biologically adaptive and precision radiotherapy and outlines priorities for their responsible and equitable integration into routine clinical practice.