e13789 Background: The patients with advanced upper gastrointestinal (UGI) cancer reported multiple symptom burdens at diagnosis and after failing multiple chemotherapy lines. Assessing the readiness of patient-reported outcome (PRO) parameters to support evidence-based pathways for monitoring and managing outpatients is an unmet clinical need to integrate PRO into routine outpatient care for UGI cancer patients. This study aims to identify the most relevant PRO parameters that represent the high symptom burden and functioning impairment overtime during chemotherapy for advanced UGI cancer. Methods: Eligible UGI adult cancer patients (N=111) for a new line of chemotherapy were enrolled. Multiple symptoms were assessed electronically for 36 weeks, using The M.D. Anderson Symptom Inventory GI module (MDASI-GI). Longitudinal symptoms burden was analyzed using mixed-effect models adjusted for age, sex, performance status (PS) (good vs. poor PS ( ECOG 0-1 vs. 2-4). Results: Patients who contributed with more than baseline PROs were included in the analysis (n=92). Of those patients, 43 were treatment-naïve, and 49 had received prior therapy. The primary tumor sites include esophageal (32%), gastroesophageal junction (GEJ) (25%), or gastric (40%). All patients at baseline reported the following symptoms at a severe level (score ≥7 on a 0-10 MDASI-GI scale): fatigue, lack of appetite, pain, disturbed sleep, drowsy, and inability to eat. There was no significant difference in the composite score of these symptoms overtime, regardless of disease groups or treatment status at baseline. Patients with poor PS reported a statistically significant severe composite score baseline ( P=.04). Patients who stayed longer in the study during their survivorship reported a decreased prevalence of moderate to severe symptoms (score of ≥ 4) from 51% at baseline to 40% at 12 weeks, 34% at 24 weeks, and to 28% at 36 weeks. Over time, treatment naïve patients had more severe numbness/tingling, while previously treated group had more severe distress. Conclusions: This longitudinal prospective study during survivorship in patients undergoing chemotherapy for advanced UGI cancer provides a set of most distressing symptom burdens that need to be monitored as part of outpatient care. These data support establishing symptom management pathways for routine use of ePRO for screening and triage of, and linking those symptoms to toxicities after chemotherapy for UGI cancer patients.