Longitudinal Associations of Chemotherapy-Induced Symptom Clusters with Healthcare Utilization and Mortality among Patients with Gastrointestinal Cancers

Background: Chemotherapy (ChT) induced neurological and gastrointestinal (GI) symptom clusters are common, but their longitudinal associations with healthcare utilization and mortality remain unclear. Methods: We conducted a retrospective study of 973 GI cancer patients at Mass General Brigham Health System from 2019 to 2024. Patient-reported symptoms were routinely collected at ChT initiation, days 30, 60, or 90. Primary outcomes were all-cause urgent care visits, emergency department (ED) visits, and death within one year of ChT. Neurological cluster was defined by the presence of fatigue, insomnia, paresthesia, and pain. GI cluster included constipation, decreased appetite, diarrhea, nausea, and vomiting. Time-to-event analysis was used to predict each outcome based on changes in neurological and GI clusters over the first 90 days of ChT. We also examined whether findings varied by age group, comorbidity level, duration of diagnosis, cancer stage and site. Results: Over time, the burden of neurological symptoms was significantly higher than that of GI symptoms. Higher neurological burden was associated with an increased risk of urgent care visits (Adjusted HR: 1.27 [95% CI: 0.97,1.67]), but not ED visits or death, with stronger associations in older adults and those without comorbidities. In contrast, higher GI burden was associated with greater risks of ED visits (Adjusted HR: 1.10 [95% CI: 1.02,1.19]) and death (Adjusted HR: 1.08 [95% CI: 0.94,1.24]), but not urgent care visits, with stronger effects in older adults, patients with comorbidities, and those with advanced cancers. Conclusions: Short-term changes in neurological and GI clusters exhibited differential associations with long-term healthcare utilization and mortality.