MR radiomics and neoadjuvant chemo-responsiveness with insights into selective treatment de-intensification in HPV-positive oropharyngeal carcinoma.

6085 Background: In HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), patients with good response to neoadjuvant chemotherapy (NAC) exhibit superior prognosis. Accurate prediction of NAC response allows for NAC candidate selection and personalized treatment de-intensification in HPV-positive OPSCC. In this study, we aimed to apply baseline magnetic resonance (MR) radiomic features to predict NAC response and prognosis. Methods: Pre-treatment MR images and clinical data of 131 patients with HPV-positive OPSCC were retrieved from Fudan University Shanghai Cancer Center. Radiomic features of both oropharyngeal lesions and metastatic nodes were extracted on T2WI and contrast-enhanced T1WI sequence. Patients were divided into training cohort (n=47), prospective validation cohort (n=49) and real-world validation cohort (n=35). Following radiomic feature selection, a linear support vector machine (SVM) model was built and validated for NAC response prediction. Nomograms that combined radiomics and clinical characteristics were then developed to predict survival outcomes. The performance of response models was assessed by the area under the curve (AUC), accuracy, sensitivity, specificity and prognostic models were measured by C-index. RNA-seq and proteomic data were further leveraged and compared to interpret the molecular features underlying radiomic signatures with differential NAC response. Results: For NAC response prediction, the fusion model with both oropharyngeal and nodal radiomic signatures on multi-sequence MR images achieved encouraging performance to predict good responders in the training cohort (AUC 0.89, 95% CI, 0.79-0.95) and prospective validation cohort (AUC 0.71, 95% CI, 0.59-0.83). For prognosis prediction, radiomics-based nomograms exhibited satisfactory discriminative ability between low-risk and high-risk patients in training cohort and two validation cohorts (PFS, C-index: 0.85, 0.76 and 0.83; OS, C-index: 0.79, 0.76 and 0.87). An exploratory analysis in the prospective validation cohort showed that de-intensified radiotherapy after NAC in low-risk patients yielded 100% in both PFS and OS. Furthermore, expression analysis unveiled distinct molecular phenotypes in relation to NAC response, where poor responders had predominantly enhanced keratinization while good responders were featured by stronger innate and adaptive immune response. Conclusions: The MR-based radiomic models and subsequent prognostic models efficiently discriminate among patients with different NAC response and survival risk. This study provides a new strategy for patient selection in HPV-positive OPSCC that are suitable for personalized de-intensification. Integration of radiomics in future trials is warranted.