ABSTRACT Approximately 66,000 individuals will be diagnosed with head and neck cancer (HNC) in the United States (US) in 2022. Most patients with HNC are treated aggressively with multi-modal therapies that have improved survival but at a human cost of substantial symptom burden, decreased health-related quality of life (HRQoL), and extensive acute care use. Symptom management for patients with HNC is critical. However, up to 50% of patients' symptoms go undetected and electronic health records (EHR) documentation of symptoms is incomplete. Ground-breaking research shows patient-reported symptom (PRO) monitoring during cancer care is associated with improved symptom control, decreased acute care use, and longer survival. Yet, a closer investigation of the literature finds the effects of PROs on cancer outcomes vary depending on implementation. Reasons for variations in PRO implementation include limited integration with electronic health records (EHR), inequality in access, and lack of standardized approaches, creating barriers to widespread implementation of PROs. We developed the NYU Electronic Patient Visit Assessment (ePVA) for HNC as a valid, reliable PRO that has evolved into a clinical support tool for early detection of uncontrolled symptoms. The ePVA provides a global picture of the patient's condition automated to clinicians at point-of-care, enabling real-time interventions. We completed a pilot randomized clinical trial of the ePVA in 32 patients with HNC undergoing radiation therapy (RT) with or without chemotherapy, and found those assigned to the ePVA+Usual Care Arm reported significantly less severe HNC symptoms (p<.05) and acute care use (p<.001) than those assigned to the Usual Care Arm. Our objective in this proposal is to identify implementation strategies optimizing the effectiveness of the ePVA to improve HNC outcomes in real-world settings and explore integrating the ePVA with the EHR architecture for scalability and equality in access. To achieve this objective, we will conduct a mixed methods hybrid type I study at three National Cancer Institute-Designated Comprehensive Cancer Centers serving diverse populations in rural and urban settings (New York University, University of Kansas Cancer Center, Fox Chase Cancer Center) using the RE-AIM framework. For participants with HNC undergoing RT with or without chemotherapy, the specific aims are: 1) (Quantitative) Determine the effect of the Electronic Patient Visit Assessment (ePVA) on HNC symptoms (primary outcomes), pain, HRQoL, and acute care use (secondary outcomes) in a two-arm (usual care vs. ePVA+usual care) multisite randomized clinical trial (n=270); 2) (Qualitative) Examine HNC patients’ and clinicians’ perspectives on patient, clinician, and organization facilitators and barriers to the ePVA’s reach, adoption, effectiveness, and maintenance; 3) (Integrated) Identify implementation strategies optimizing ePVA’s reach, adoption, effectiveness, and maintenance; Explor...