Rawal, Shalin

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

8075 Background: The role of definitive local thoracic therapy in metastatic non–small cell lung cancer (NSCLC) remains controversial. While stereotactic body radiation therapy (SBRT) is increasingly utilized, comparative survival outcomes with surgical resection in real-world populations remain limited. We evaluated survival and pulmonary outcomes associated with surgery versus SBRT in patients with stage IV NSCLC. Methods: We conducted a retrospective cohort study using the TriNetX Research Network including adults (≥18 years) with stage IV NSCLC treated between January 2013 and December 2023 who underwent definitive local thoracic therapy with either surgical resection or SBRT. Patients with small cell lung cancer, prior lung cancer diagnoses, prior thoracic radiation, or incomplete survival data were excluded. Propensity score matching (1:1) was performed to balance demographics, comorbidities, smoking history, and exposure to systemic therapy including chemotherapy and immunotherapy within 6 months of index treatment. Primary outcomes included landmark 1-year all-cause mortality and overall survival. Secondary outcomes included pneumonia and respiratory failure. Kaplan–Meier analysis and Cox proportional hazards regression were performed. Results: After matching, 1,934 patients were included (967 per cohort). At 1 year, surgical resection was associated with significantly lower mortality compared with SBRT (17.5% vs 31.4%; RR 0.56, 95% CI 0.47–0.66; p < 0.001), corresponding to an absolute risk reduction of 13.9% and an estimated number needed to treat of approximately 7. Kaplan–Meier analysis demonstrated superior survival in the surgical cohort (log-rank p < 0.001). Surgical resection remained associated with significantly improved long-term survival, with a 64% lower hazard of death (HR 0.36, 95% CI 0.30–0.44; p < 0.001) and prolonged median survival (3,942 vs 1,182 days). Pulmonary outcomes favored surgery. Pneumonia incidence was significantly lower in the surgical cohort at both 1 year (12.9% vs 29.3%; RR 0.44; p < 0.001) and 3 years (5.9% vs 14.2%; RR 0.42; p < 0.001). Rates of respiratory failure did not differ significantly between treatment groups. Conclusions: In this large real-world propensity-matched study, surgical resection was associated with significantly improved survival compared with SBRT in carefully selected patients with stage IV NSCLC. Surgery was additionally associated with lower long-term pulmonary infectious complications without increased respiratory failure risk. These findings suggest a potential role for aggressive local therapy in selected metastatic patients and support prospective trials to refine patient selection strategies.

3605 Background: Metabolic status and systemic inflammation are increasingly recognized as important modifiers of immune checkpoint inhibitor (ICI) response. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exhibit anti-inflammatory and immunomodulatory properties and are widely used in diabetes and obesity. However, their clinical impact on immunotherapy outcomes in metastatic colorectal cancer (mCRC) remains unclear. Methods: We conducted a retrospective observational cohort study using the TriNetX Global Collaborative Network, including electronic health records from 170 healthcare organizations between 2015 and 2025. Adults with mCRC who received at least one ICI were identified. Patients prescribed GLP-1 RAs within six months before or after ICI initiation were compared with non-exposed controls. Patients with prior bariatric surgery were excluded. Cohorts were balanced using 1:1 propensity score matching for demographics, metabolic conditions, and major comorbidities. Primary endpoint was all-cause mortality at 1, 3, and 5 years. Secondary outcomes included pneumonia, heart failure exacerbation, and major abdominal surgical procedures. Survival analyses were performed using Kaplan–Meier methods and Cox proportional hazards models. Results: Among 8,304 eligible patients, 148 received GLP-1 RAs. After propensity matching, 138 patients were included in each cohort with well-balanced baseline characteristics. At 1 year, mortality was lower in the GLP-1 cohort (27.5% vs 40.6%), corresponding to a 32% relative risk reduction (RR 0.68, 95% CI 0.49–0.95) and reduced hazard of death (HR 0.67, 95% CI 0.43–1.03). This association persisted at 3 years (27.5% vs 41.3%; RR 0.67, 95% CI 0.48–0.93; HR 0.68, 95% CI 0.45–1.05) and 5 years (28.3% vs 42.0%; RR 0.67, 95% CI 0.49–0.93), with higher 5-year survival probability (50.5% vs 41.5%). Secondary outcomes favored GLP-1 exposure, including lower incidence of pneumonia (10.9% vs 17.4%; HR 0.58) and fewer heart failure exacerbations (23.9% vs 31.9%; HR 0.75). Rates of major abdominal surgical procedures were numerically lower in the GLP-1 cohort. Conclusions: In this large real-world cohort, concurrent GLP-1 RA exposure was associated with clinically meaningful and durable survival benefit in mCRC patients receiving ICIs, without increased adverse clinical outcomes. These findings suggest a potential immunometabolic interaction and support prospective evaluation of GLP-1–based strategies as adjunctive modifiers of immunotherapy response.