PurposeWe sought to develop an effective combined model for predicting the survival of patients with diffuse large B-cell lymphoma (DLBCL) based on the multimodal PET-CT deep features radiomics signature (DFR-signature).Methods369 DLBCL patients from two medical centers were included in this study. Their PET and CT images were fused to construct the multimodal PET-CT images using a deep learning fusion network. Then the deep features were extracted from those fused PET-CT images, and the DFR-signature was constructed through an Automated machine learning (AutoML) model. Combined with clinical indexes from the Cox regression analysis, we constructed a combined model to predict the progression-free survival (PFS) and the overall survival (OS) of patients. In addition, the combined model was evaluated in the concordance index (C-index) and the time-dependent area under the ROC curve (tdAUC).ResultsA total of 1000 deep features were extracted to build a DFR-signature. Besides the DFR-signature, the combined model integrating metabolic and clinical factors performed best in terms of PFS and OS. For PFS, the C-indices are 0.784 and 0.739 in the training cohort and internal validation cohort, respectively. For OS, the C-indices are 0.831 and 0.782 in the training cohort and internal validation cohort.ConclusionsDFR-signature constructed from multimodal images improved the classification accuracy of prognosis for DLBCL patients. Moreover, the constructed DFR-signature combined with NCCN-IPI exhibited excellent potential for risk stratification of DLBCL patients.