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The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing. Disease stage and smoking history are often used in current clinical trials to select patients for deintensification therapy, but these features lack sufficient accuracy for predicting disease relapse. Our purpose was to develop an imaging signature to assess early response and predict outcomes of OPSCC. Methods: We retrospectively analyzed 162 OPSCC patients treated with concurrent chemoradiotherapy, equally divided into separate training and validation cohorts with similar clinical characteristics. A robust consensus clustering approach was used to spatially partition the primary tumor and involved lymph nodes into subregions (i.e., habitats) based on 18 F-FDG PET and contrast CT imaging. We proposed quantitative image features to characterize the temporal volumetric change of the habitats and peritumoral/nodal tissue between baseline and midtreatment. The reproducibility of these features was evaluated. We developed an imaging signature to predict progression-free survival (PFS) by fitting an L1-regularized Cox regression model. Results: We identified 3 phenotypically distinct intratumoral habitats: metabolically active and heterogeneous, enhancing and heterogeneous, and metabolically inactive and homogeneous. The final Cox model consisted of 4 habitat evolution-based features. In both cohorts, this imaging signature significantly outperformed traditional imaging metrics, including midtreatment metabolic tumor volume for predicting PFS, with a C-index of 0.72 versus 0.67 (training) and 0.66 versus 0.56 (validation). The imaging signature stratified patients into high-risk versus low-risk groups with 2-y PFS rates of 59.1% versus 89.4% (hazard ratio, 4.4; 95% confidence interval, 1.4-13.4 [training]) and 61.4% versus 87.8% (hazard ratio, 4.6; 95% confidence interval, 1.7-12.1 [validation]). The imaging signature remained an independent predictor of PFS in multivariable analysis adjusting for stage, human papillomavirus status, and smoking history. Conclusion: The proposed imaging signature allows more accurate prediction of disease progression and, if prospectively validated, may refine OPSCC patient selection for risk-adaptive therapy.

Purpose: Prognostic biomarkers of disease relapse are needed for risk-adaptive therapy of oropharyngeal cancer (OPC). This work aims to identify an imaging signature to predict distant metastasis in OPC.Materials/Methods: This single-institution retrospective study included 140 patients treated with definitive concurrent chemoradiotherapy, for whom both pre and mid-treatment contrastenhanced CT scans were available. Patients were divided into separate training and testing cohorts. Forty-five quantitative image features were extracted to characterize tumor and involved lymph nodes at both time points. By incorporating both imaging and clinicopathological features, a random survival forest (RSF) model was built to predict distant metastasis-free survival (DMFS). The model was optimized via repeated cross-validation in the training cohort, and then independently validated in the testing cohort.

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