Sociodemographic disparities in sepsis-associated mortality among patients with gastrointestinal malignancies in the United States, 1999-2020.

e23077 Background: Patients with gastrointestinal (GI) malignancies are increasingly treated with multimodal systemic and procedural therapies, including cytotoxic chemotherapy, immune checkpoint inhibitors, and corticosteroids for treatment-related toxicities, which can compromise immune function and increase the risk of severe infections. However, population-level trends and sociodemographic disparities in sepsis-associated mortality among patients with GI malignancies in the contemporary treatment era remain incompletely characterized. This study evaluates long-term mortality trends for sepsis among patients with gastrointestinal malignancies. Methods: We analyzed U.S. death certificate data from the CDC WONDER database (1999–2020) for adults aged ≥25 years with gastrointestinal malignancies (ICD-10 C15–C26) listed as the underlying cause of death and sepsis (A40.0–A41.9) listed as a contributing cause. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CI), stratified by sex, race/ethnicity, U.S. census region, and urban–rural residence. Results: From 1999 to 2020, 140,650 deaths were identified among patients with GI malignancies and sepsis. Sepsis-associated mortality increased over time, with AAMRs rising from 2.98 in 1999 to 3.35 in 2020 (AAPC 0.83%, 95% CI, 0.44–1.22). Mortality rates were significantly higher in males than females (3.82 vs 2.22), with the most significant rise in male mortality occurring between 2012 and 2020 (APC 2.62, 95% CI, 1.84–3.40). Racial disparities were evident with consistently higher mortality rates observed among African American individuals throughout the study period (AAMR 4.77) as compared to Hispanics (3.41), Asians (3.36), American Indians (2.91), or Whites (2.71). Regionally, the South exhibited the greatest rise in mortality (AAPC 1.38%, 95% CI 0.88–1.88). Although large metropolitan areas had higher absolute mortality, rural populations experienced the sharpest increase in mortality over time (AAPC 1.81%, 95% CI 1.25–2.38). Conclusions: Sepsis-associated mortality in patients with GI malignancies has risen steadily in the United States over the past two decades, with a disproportionate burden among males, African Americans, and rural populations despite advances in cancer therapy. These findings underscore gaps in treatment-associated supportive oncology care, and structural factors influencing access to infection surveillance and timely access to high acuity care. This highlights the need for targeted interventions to diagnose and treat early sepsis, especially in vulnerable populations, to reduce preventable mortality in the modern era of GI cancer management.