Abstract Image texture analysis (radiomics) uses radiographic images to quantify characteristics that may identify tumour heterogeneity and associated patient outcomes. Using fluoro‐deoxy‐glucose positron emission tomography/computed tomography (FDG‐PET/CT)‐derived data, including quantitative metrics, image texture analysis and other clinical risk factors, we aimed to develop a prognostic model that predicts survival in patients with previously untreated diffuse large B‐cell lymphoma (DLBCL) from GOYA (NCT01287741). Image texture features and clinical risk factors were combined into a random forest model and compared with the international prognostic index (IPI) for DLBCL based on progression‐free survival (PFS) and overall survival (OS) predictions. Baseline FDG‐PET scans were available for 1263 patients, 832 patients of these were cell‐of‐origin (COO)‐evaluable. Patients were stratified by IPI or radiomics features plus clinical risk factors into low‐, intermediate‐ and high‐risk groups. The random forest model with COO subgroups identified a clearer high‐risk population (45% 2‐year PFS [95% confidence interval (CI) 40%–52%]; 65% 2‐year OS [95% CI 59%–71%]) than the IPI (58% 2‐year PFS [95% CI 50%–67%]; 69% 2‐year OS [95% CI 62%–77%]). This study confirms that standard clinical risk factors can be combined with PET‐derived image texture features to provide an improved prognostic model predicting survival in untreated DLBCL.
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