Nookala, Vinod

e16598 Background: Brain metastases occur in a substantial proportion of patients with renal cell carcinoma (RCC) and are associated with poor prognosis. Stereotactic radiosurgery (SRS) is frequently used for intracranial disease control; however, contemporary real-world survival outcomes and the influence of systemic therapy exposure and metastatic burden remain incompletely characterized. Methods: We conducted a retrospective observational study using the TriNetX global federated health research network. Adult patients (≥18 years) with RCC and documented brain metastases who underwent stereotactic radiosurgery between January 2013 and December 2023 were identified. The index date was defined as the date of first SRS. Baseline demographics, comorbidities, and prior systemic therapy exposure including immune checkpoint inhibitors and VEGF-targeted therapies within 6 months before SRS were assessed. Metastatic burden was approximated using the number of distinct extracranial metastatic organ sites (single-organ vs multi-organ involvement). Overall survival (OS) was evaluated using Kaplan–Meier methods. Results: A total of 232 patients with RCC and brain metastases treated with SRS were included. Mean age was 61.2 ± 10.6 years, and 72% were male. Common comorbidities included hypertension (53%), diabetes mellitus (30%), chronic kidney disease (28%), and cerebrovascular disease (26%). Prior to SRS, 78% of patients received systemic therapy, including immune checkpoint inhibitors (49%) and VEGF-targeted therapies (46%). Using organ-site count as a proxy for disease burden, 59% demonstrated single-organ extracranial metastatic involvement. During follow-up, 95 patients (40.9%) experienced all-cause mortality. Median overall survival was 967 days (31.8 months). Estimated long-term survival probability at maximum follow-up was 21.2%. Kaplan–Meier analysis demonstrated early survival attrition followed by prolonged survival in a subset of patients. Patients receiving immunotherapy and those with limited extracranial metastatic burden demonstrated more favorable survival patterns. Conclusions: In this large contemporary real-world cohort of RCC patients with brain metastases treated with stereotactic radiosurgery, median overall survival exceeded 2.5 years, providing important modern survival benchmarks. Favorable outcomes were observed among patients receiving systemic immunotherapy and those with limited metastatic burden, supporting the continued role of SRS within multidisciplinary management strategies for selected patients with metastatic RCC.

e16469 Background: Pancreatic cancer remains among the most lethal malignancies worldwide, with limited improvement in survival despite therapeutic advances. Contemporary real-world data characterizing recent diagnosis acceleration, demographic disparities, and future burden remain limited. We evaluated national trends in pancreatic cancer burden using a large federated electronic health record (EHR) network. Methods: We conducted a retrospective multicenter real-world cohort analysis using the TriNetX Research Network. Adult patients (≥18 years) with pancreatic cancer were identified using ICD-10-CM code C25. Annual newly recorded diagnosis proportions, prevalence, and incidence rates were calculated for calendar years 2020–2024 and stratified by age, sex, race, and ethnicity. New diagnoses were defined as first recorded pancreatic cancer encounters within each calendar year. Exploratory future burden projections were generated through 2028 using autoregressive integrated moving average (ARIMA) time-series modeling. Results: Between 2020 and 2024, newly recorded pancreatic cancer diagnoses increased from 0.032% (21,118 cases) to 0.046% (23,660 cases), representing a descriptive relative increase exceeding 40%. Prevalence increased from 0.101% (65,971 cases) to 0.145% (74,139 cases), reflecting rapid expansion of disease burden. Diagnosis burden increased markedly with advancing age, with the highest burden observed among individuals aged ≥65 years. Males consistently demonstrated higher diagnosis proportions compared with females. Racial stratification demonstrated higher recorded diagnosis proportions among White and Asian populations, while substantial prevalence burden persisted across all racial groups, potentially reflecting differences in healthcare utilization and access. Non-Hispanic individuals exhibited higher diagnosis and prevalence proportions compared with Hispanic individuals. Exploratory ARIMA forecasting projected continued growth in pancreatic cancer burden through 2028, with widening uncertainty intervals over time, indicating escalating long-term healthcare demand. Conclusions: Pancreatic cancer burden in the United States is rapidly increasing, with disproportionate impact among older adults and males and persistent demographic disparities. Exploratory projection modeling suggests continued expansion of disease burden in the near term. These findings highlight the urgent need for earlier detection initiatives, risk-adapted screening strategies, and healthcare system preparedness to address the growing national impact of pancreatic cancer.

e16322 Background: Small intestine neuroendocrine carcinoma (NEC) is a rare, aggressive malignancy comprising less than 0.1% of gastrointestinal cancers. Population-level data remain limited, restricting understanding of long-term survival patterns, demographic disparities, and evolving disease burden. We evaluated survival outcomes, demographic predictors, and incidence trends of small intestine NEC in the United States. Methods: We conducted a retrospective population-based cohort study using SEER Research Data (17 registries, November 2024 submission). Patients diagnosed with malignant small intestine NEC (ICD-O-3 morphology code 9.3.3.1.2) between 2000 and 2022 were identified using SEER*Stat (v9.0.4.2). Variables including age group, sex, race, year of diagnosis, survival time, and vital status were analyzed in R (v4.5.1). Overall survival (OS) was estimated using Kaplan–Meier methods and compared using log-rank testing. Cox proportional hazards models identified independent predictors of OS. Annual case counts were modeled using time-series forecasting to project future incidence. Results: A total of 506 patients were included. Estimated OS was 94.4% (95% CI 92.4–96.4) at 1 year, 88.1% (85.3–91.0) at 3 years, and 82.4% (79.0–85.9) at 5 years, with a subset demonstrating survival beyond 15 years. Increasing age was associated with worse survival (log-rank p = 0.058). Significant racial differences in OS were observed (log-rank p < 0.0001). In multivariable analysis, race remained independently associated with OS. Incidence forecasting projected a modest increase in annual case burden over the next decade. Conclusions: Small intestine NEC demonstrates heterogeneous survival outcomes, significant demographic disparities, and projected growth in disease burden. These findings highlight the need for improved risk stratification, equitable access to care, and integration of molecular and treatment-level data to optimize management of this rare malignancy

e15598 Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of gastrointestinal (GI) malignancies. Emerging evidence suggests that gut microbiome composition plays a critical role in modulating the efficacy of immunotherapy. Antibiotics, by disrupting intestinal microbial diversity, may attenuate antitumor immune responses and compromise ICI outcomes. We evaluated time-dependent clinical outcomes associated with antibiotic exposure using real-world data. Methods: We conducted a retrospective cohort study using a large federated real-world database (2015-2025). Adults (18–89 years) with gastrointestinal or hepatobiliary malignancies (including colorectal, gastric, esophageal, and liver cancers) treated with ICI, receiving systemic antibiotics, were compared with matched controls without antibiotic exposure. Cohorts were balanced using 1:1 Propensity score matching for demographics, comorbidities, and treatment variables. The primary outcome was all-cause mortality at 30 days of ICI initiation; the secondary outcomes were hospitalization secondary to infectious and organ-related complications, overall survival at 1 and 3 years. Pre-specified subgroup analyses were performed in older adults ( > / = 65 years). Effect estimates were reported as risk ratios( RR), hazard ratios (HR), and absolute risk differences. Survival was analyzed using Kaplan–Meier curves and Cox proportional hazards models. Results: Within 30 days, antibiotic exposure was associated with significantly increased risks of Clostridioides difficile infection (RR 2.39), pneumonia (RR 2.93), acute kidney injury (RR 1.40), acute respiratory failure (RR 2.11), and neutropenia (RR 1.18) (all p < 0.05). Absolute risk differences translated to a number needed to harm (NNH) of approximately 38 for pneumonia, 143 for acute kidney injury, and ~140 for C. difficile infection. One-month mortality was modestly higher in the antibiotic group (5.4% vs 4.5%; HR 1.22; p = 0.014). However, no significant differences in mortality were observed at 6 months, 1 year, or 3 years, and survival curves converged over time. In the subgroup analysis of adults ≥65 years, early adverse event patterns were preserved, while long-term mortality remained unchanged. One-year hospital admission rates did not differ significantly between groups. Conclusions: Antibiotic exposure is associated with substantial early infectious and organ-related harm and a small increase in short-term mortality, without improvement in long-term survival, including among older adults. These findings highlight a critical opportunity for risk-adapted antibiotic stewardship and careful reassessment of empiric antibiotic use. Key words: ICI- Immune checkpoint inhibitors, RR- Risk ratio, HR- Hazard Ratio, NNH- Number Needed to Harm.

11186 Background: Cancer survival is shaped by tumor biology, treatment access, and socioeconomic context, yet population-level quantification of long-term survival disparities related to chemotherapy use and income is limited. We assessed five-year cancer-specific survival across demographic, treatment, and socioeconomic strata in a national registry. Methods: We performed a retrospective, population-based survival analysis using the Surveillance, Epidemiology, and End Results (SEER) database. Cancer-specific survival was evaluated at 12, 24, 36, 48, and 60 months after diagnosis. Outcomes were stratified by sex, race, chemotherapy receipt, and area-level median household income categories. Survival estimates were summarized descriptively and visualized using time-to-event curves. Results: Overall cancer-specific survival declined progressively over five years, from ~84% at 12 months to ~58% at 60 months. Sex differences were minimal, with similar five-year survival among males and females (~57–58%). Racial disparities were substantial: Asian/Pacific Islander patients demonstrated the highest survival across follow-up, while Black and American Indian/Alaska Native patients had lower early survival and persistent gaps at five years. Patients with recorded chemotherapy use had improved survival compared with those without or with unknown chemotherapy status; 12-month survival was ~88% versus ~80%, and five-year survival was ~65% versus ~57%, respectively. A pronounced socioeconomic gradient was observed: individuals in areas with median household income ≥$120,000 had higher five-year survival (~67%), whereas those in areas with income < $40,000 had markedly lower survival (~52%). Conclusions: In this national registry analysis, both chemotherapy utilization and higher socioeconomic status were strongly associated with improved long-term cancer survival, whereas persistent racial and income-related disparities remained evident. These findings highlight ongoing inequities in access to oncologic care and support the need for targeted policy interventions and equity-focused treatment delivery models. Interpretation should account for limitations inherent to observational registry data and potential residual confounding.