Background: PROs assessing quality of life (QOL) and physical symptoms often correlate with clinical outcomes in patients (pts) with cancer. Yet, data are lacking about the use of PROs to predict treatment response. We evaluated associations of baseline PROs with treatment response, healthcare use, and survival among pts with advanced gastrointestinal cancer. Methods: We prospectively enrolled pts with metastatic gastrointestinal cancer prior to initiating chemotherapy at Massachusetts General Hospital. At baseline (start of treatment), pts reported their QOL (Functional Assessment of Cancer Therapy General [FACT-G], subscales assess QOL across 4 domains: functional, physical, emotional, social well-being) and symptom burden (Edmonton Symptom Assessment System [ESAS]). Higher scores on FACT-G indicate better QOL, while higher scores on ESAS represent a greater symptom burden. We used regression models to examine associations of baseline PRO scores with treatment response (clinical benefit [CB] or progressive disease [PD] at the time of first scan based on clinical documentation), healthcare use (unplanned hospital admissions), and survival. Results: From 5/2019-3/2020, we enrolled 112 of 131 (85.5% enrollment) consecutive pts (median age = 62.8, 61.6% male, 45.5% pancreatobiliary cancer). For treatment response, 64.3% had CB and 35.7% had PD. Higher ESAS-physical (B = 1.04, p = .027) and lower FACT-G functional (B = 0.92, p = .038) scores at baseline were significant predictors of PD. On the specific ESAS items, pts who experienced PD were more likely to report moderate/severe poor well-being (57.9% vs 29.7%; p = .001), pain (44.7% vs 25.0%; p < .050), drowsiness (42.1% vs 20.3%; p = .024), and diarrhea (23.7% vs 4.7%; p = .008) at baseline. Lower FACT-G total (HR = 0.96, p = .003), FACT-G physical (HR = 0.89, p < .001), FACT-G functional (HR = 0.87, p < .001), and higher ESAS-physical (HR = 1.03, p = .028) scores at baseline were significantly associated with greater risk of hospital admission. Lower FACT-G total (HR = 0.96, p = .009), FACT-G emotional (HR = 0.87, p = .014), as well as higher ESAS-total (HR = 1.03, p = .018) and ESAS-physical (HR = 1.03, p = .040) scores at baseline were significantly associated with greater risk of death. Conclusions: We found that baseline PROs predict treatment response in pts with advanced cancer, namely physical symptoms and functional QOL, in addition to healthcare use and survival outcomes. These findings further support the use of PROs to predict important clinical outcomes, including the novel finding of treatment response.