Longitudinal Patterns of Symptoms in Patients Undergoing Chemotherapy

Importance: The longitudinal patterns of patient-reported outcomes and their association with mortality in routine oncology care are largely unexplored. Objectives: To characterize the longitudinal patient-reported outcomes among patients undergoing chemotherapy and evaluate their association with mortality. Design, Setting, and Participants: This secondary analysis assessed patients in the intervention arm of a cluster randomized clinical trial conducted by the Symptom Management Implementation of Patient Reported Outcomes in Oncology (SIMPRO) consortium. Patients with gastrointestinal, gynecologic, or thoracic cancer who started a new chemotherapy regimen and completed at least 1 symptom questionnaire within 180 days at medical oncology clinics at 6 hospitals (Northeast and Southern US) were assessed from September 1, 2019, to August 31, 2023. Data analysis was performed from March to September 2025. Exposure: Electronic health record-integrated symptom questionnaires along with patient education, decision support alerts, and clinical reports to facilitate symptom management. Main Outcomes and Measures: Outcomes were patient-reported symptoms, physical function, overall well-being, and mortality. Multivariable regression identified factors associated with mortality during the 180-day follow-up period with symptoms included as time-varying covariates. Results: Overall, 3735 patients (median [IQR] age, 67 [59-74] years; 2196 [59%] female) submitted 35 059 symptom questionnaires; 1710 (46%) were diagnosed with gastrointestinal, 1163 (31%) with thoracic, and 852 (23%) with gynecologic cancer. On multivariable analysis, moderate (hazard ratio [HR], 2.07; 95% CI, 1.34-3.20; P < .001) and severe (HR, 3.39; 95% CI, 2.20-5.22; P < .001) physical function deficits were associated with a higher hazard of death. Fatigue was the most common symptom reported (29 138 [83%]) followed by pain (19 959 [57%]). The prevalence of severe symptom reports decreased from 1440 of 30 660 reported symptoms (5%) in week 1 to 40 of 3528 reported symptoms (1%) in week 26, whereas moderate symptom reports decreased from 3522 of 30 660 symptoms (11%) to 265 of 3528 (8%). Other time-varying factors associated with higher hazard of death were moderate pain (HR, 1.43; 95%, CI 1.08-1.90; P = .01), severe pain (HR, 1.66; 94% CI, 1.21-2.26; P = .001), moderate dyspnea (HR, 1.31; 95% CI, 1.02-1.69; P = .04), severe dyspnea (HR, 1.62; 95% CI, 1.17-2.24; P = .004), moderate loss in appetite (HR, 1.40; 95% CI, 1.02-1.92; P = .04), and severe loss in appetite (HR, 2.27; 95% CI, 1.55-3.33; P < .001). Conclusions and Relevance: This secondary analysis of a cluster randomized clinical trial of patients with cancer characterized the burden of cancer-related symptoms and described normative experiences for patients receiving chemotherapy for 3 common types of cancer and found that mortality was associated with patients' evolving health status. These findings may help inform programs to monitor and manage symptoms and to deliver targeted interventions that enhance outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03850912.