Background: Health systems have begun using electronic patient reported outcomes (ePROs) to evaluate and ideally mitigate patients’ symptom burden following treatment for cancer and other conditions. However, the optimal number of symptoms and approach to capturing this information is unknown. We hypothesized that self-reported overall wellbeing (OWB) and physical function (PFN) would provide distinctive information, beyond that described by a multi-item symptom questionnaire, and augment the clinical utility of an ePRO system. Methods: eSyM, an EHR-integrated symptom management program, was deployed across six health systems for patients receiving chemotherapy or surgery for a suspected or confirmed thoracic, gastrointestinal, or gynecologic malignancy. eSyM prompts patients to complete a 12-item symptom questionnaire 2-3 times per week. This questionnaire also includes two pictogram questions that assess OWB and PFN – each scored using a four-point scale from 0 (best) to 3 (worst). We sought to identify patient characteristics associated with the lowest OWB and PFN (i.e., score = 3), to describe Spearman correlations between OWB and PFN, and to elucidate the relationships between symptom scores and OWB/PFN. Ordinal logistic regression models were used to adjust for potential confounding. Results: From September 2019-December 2022, 9753 patients submitted 75,166 questionnaires. There were 3846 chemotherapy patients (median age 66, 58% female, 17% non-white) and 5907 surgery patients (median age 61, 73% female, 7% non-white). The plurality of responses indicated mild impairment for OWB and PFN (Table). OWB and PFN scores were moderately correlated with each other (chemotherapy 0.62; surgery 0.59); with the sum of all symptom scores for chemotherapy (OWB 0.48, PFN 0.45) and surgery (OWB 0.51, PFN 0.45) patients; and with pain, fatigue, and anorexia (correlation coefficients 0.40-0.61). No individual symptoms were strongly correlated (coefficient > 0.7) with OWB or PFN. After controlling for other factors, OWB and PFN scores varied significantly by health system. Patients with disability were more likely to report low OWB and PFN (ORs 1.99-3.26; p < 0.05) versus other employment statuses. Conclusions: In a large cohort of chemotherapy and surgery patients from six community-based cancer centers, self-reported OWB and PFN scores were moderately correlated with common symptoms. These items offer discriminant and face validity and provide distinctive information that supplements a multi-item symptom questionnaire. Routine use of OWB and PFN can guide management strategies for symptomatic cancer patients. Clinical trial information: NCT03850912.