Valentina Formica

Background/Objectives: Radiogenomics integrates quantitative imaging features with genomic and molecular data to better characterize tumor biology and support precision oncology. While extensively investigated in solid tumors, its application to hematologic malignancies remains relatively unexplored despite the widespread use of advanced imaging in lymphoma and multiple myeloma. Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched up to December 2025 for studies investigating radiogenomic associations in hematologic malignancies. Study quality was assessed using PROBAST and METRICS. Two reviewers independently screened all records and performed data extraction through consensus. Results: Twelve studies were included, covering multiple myeloma and various lymphoma subtypes (aggressive B-cell lymphoma, classical Hodgkin lymphoma, and primary CNS lymphoma). Imaging modalities included PET/CT, MRI and CT. Across studies, radiomic and imaging-derived features were associated with cytogenetic abnormalities, gene expression profiles, and circulating tumor DNA metrics. In multiple myeloma, MRI and CT-based radiomics showed promising ability to predict high-risk cytogenetic abnormalities. In lymphoma, PET-derived volumetric and dissemination features correlated with molecular risk profiles and tumor microenvironment characteristics. Several studies demonstrated improved prognostic performance when imaging features were combined with genomic or clinical variables. Conclusions: Radiogenomic approaches in hematologic malignancies show promising potential for non-invasive risk stratification and improved prognostic assessment. However, current evidence remains limited by small cohorts, heterogeneous methodologies, and a lack of external validation. Prospective multicenter studies and standardized imaging–genomic pipelines will be essential to enable clinical translation.