Leveraging Interradiomic Feature Relationships for Enhanced Prediction of Distant Metastasis and Characterization of Heterogeneity in Head and Neck Cancer.

PurposeDistant metastasis remains a major cause of treatment failure in head and neck (HN) cancer, highlighting the need for more accurate early risk stratification. This study developed and validated a deep radiomics framework to characterize tumor heterogeneity from pretreatment computed tomography (CT) images and improve prediction of distant metastasis-free survival (DMFS).Methods and materialsThis multicenter study included 3421 patients with HN cancer from 4 cohorts across 12 institutions. Radiomics features were extracted from primary tumors and transformed into OmicsMaps, a structured representation that spatially organizes interfeature relationships to facilitate learning of complex prognostic patterns. A convolutional neural network was trained to derive prognostic signatures, which were integrated with key clinical variables to construct an OmicsMap-clinical fusion model for patient risk stratification. Model performance was assessed using the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) in the CT Images from Large Head and Neck Cohort (RADCURE), HEAD-NECK-RADIOMICS-HN1 (HN1), and Head-Neck-Positron Emission Tomography-Computed Tomography (HN-PET-CT) cohorts. Radiogenomic analyses using RNA-seq data were conducted in the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) cohort to investigate biological characteristics associated with the imaging-defined risk groups.ResultsThe OmicsMap achieved C-index values of 0.742, 0.768, and 0.671 in the RADCURE, HN1, and HN-PET-CT cohorts, outperforming the conventional radiomics approach by 5.40%-6.37%. Incorporating clinical variables further improved generalizability, yielding a C-index of 0.864 (HN1) and 0.730 (HN-PET-CT), with time-dependent AUC of 0.727-0.895. The fusion model consistently stratified patients into distinct high- and low-risk groups for both DMFS and overall survival across cohorts (P