522 Background: AEN is a rare malignancy ranging from indolent well-differentiated carcinoma to highly aggressive signet ring carcinoma. Optimal therapy is cytoreductive surgery (CRS) followed by heated intraperitoneal chemotherapy (HIPEC). Yet some patients (pts) are suboptimal for CRS/HIPEC, and are considered for SC. We have previously reported our retrospective analysis suggesting overall survival (OS) benefits from SC. We then opted to assess the impact of SC on QOL in unresectable AEN pts for which no standard of care exists. Methods: 50 pts who initiated SC were prospectively enrolled at our institution between Oct. 2008 and Nov. 2011. EORTC (3.0) QLQ-C30 and QLQ-OV28 surveys were provided at baseline and quarterly for one year. Data were analyzed with Linear Fixed Effects models using SAS Proc Mixed. Baseline and 6 month follow-up scores were tested separately for all QOL outcomes. Subscale means were converted to scaled values from 0 to 100. Positive change over the interval indicated improvement, except in symptom scales where positive change indicated worsening symptomatology. Results: 26 pts (52%) were male, median age was 64 (37-80). All pts received 5-FU-based treatment, and 37 (74%) received a biologic agent. 18 pts (36%) had poorly differentiated histology. Statistically significant change was noted in 2 subscales (Table). Overall, the Global subscale demonstrated no significant change from baseline (MME=2.9095, p=0.4422). Conclusions: In light of the possible OS benefit of systemic treatment in unresectable AEN as previously presented, our data suggest that palliative SC does not decrease QoL and in fact correlates with improved emotional well-being, and diminished symptoms including myalgias, arthragias and weakness. Awareness of these clinical and psychiatric results will better enable clinicians to ensure optimal outcomes for their AEN patients while on treatment.[Table: see text]