Shah, Vedant

e16586 Background: Guideline-discordant care disproportionately affects racial minorities, uninsured, and underinsured patients, yet prior studies lack quantification of absolute survival time lost. We evaluated equity-adjusted survival penalties from non-adherence to guideline-concordant therapy in muscle-invasive bladder cancer (MIBC). Methods: From the National Cancer Database, we identified patients with non metastatic muscle invasive bladder cancer (cT2 to T4a, N0 or N1, M0). Overall survival was defined from diagnosis to death or last contact. Guideline-concordant therapy was defined as radical cystectomy (± perioperative systemic therapy) or trimodality therapy (definitive bladder radiotherapy with chemotherapy); all other patterns were classified as discordant. Of 55,873 eligible patients, 28,025 received concordant therapy (27,401 cystectomy; 524 trimodality therapy) and 27,848 received discordant careInverse probability of treatment weighting (IPTW) was used to balance demographic, socioeconomic, facility, tumor, and temporal covariates. We analyzed survival using weighted Kaplan-Meier and Cox models censored at 36 and 60 months. Equity-adjusted survival penalties were calculated as the difference between observed survival and counterfactual survival predicted from concordant-only models. Restricted mean survival time losses were extrapolated to years lost per 1,000 patients. Results: Guideline concordance was associated with significantly improved survival (36-month HR 0.64; 60-month HR 0.68; both p < 0.01). Among concordant modalities, radical cystectomy conferred an early survival advantage over trimodality therapy at 36 months (HR 0.23; p < 0.05) which dissipated by 60 months (HR 0.53; p > 0.05). Survival penalties were most severe for vulnerable populations. At 36 months, uninsured patients incurred a 0.90-month survival penalty (75.0 life-years lost per 1,000 patients). By 60 months, penalties widened: uninsured patients lost 1.94 months (161.7 life-years/1,000), Filipino patients lost 1.53 months (127.0/1,000), Medicaid beneficiaries lost 0.97 months (80.8/1,000), and patients at community cancer programs lost 0.21 months (54.1/1,000). Conclusions: In this national cohort of 55,873 patients, guideline concordance reduced the propensity-weighted risk of death by 32% to 36% at 3 and 5 years. However, non-adherence results in substantial absolute survival losses for marginalized groups. By quantifying these "survival penalties," we demonstrate that targeting the factors underlying discordance offers a direct opportunity to reduce inequities and achieve measurable population-level survival gains in MIBC.

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

590 Background: The landmark FAST-Forward trial demonstrated that ultra-hypofractionated whole-breast irradiation with 26 Gy in 5 fractions over 1 week was non-inferior to 40 Gy in 15 fractions for local control (HR 0.67, 95% CI 0.38–1.16), with similar normal tissue effects at 5 years. In response, major international guidelines incorporated 26 Gy in 5 fractions as a standard approach or recommended option for selected patients. Despite robust randomized evidence and guideline endorsement, U.S. real-world adoption patterns and equity of uptake across patient populations remain incompletely characterized. This study evaluated national trends in 5-fraction breast radiotherapy and sociodemographic differences from 2020 to 2023. Methods: The National Cancer Database radiotherapy fractionation fields were used to identify radiotherapy (RT) courses with evaluable fraction counts, and a binary indicator for 5-fraction RT (yes/no) was created. Temporal trends by diagnosis year (2020–2023) were assessed, and associations between 5-fraction RT and sociodemographic factors (primary insurance, urban or rural status, neighborhood income quartile, and race) were examined using chi-square testing. Results: Among 536,783 RT courses with complete data from 2020 to 2023, use of 5-fraction RT increased substantially over time: 4.3% in 2020, 8.1% in 2021, 12.7% in 2022, and 17.4% in 2023, resulting in an overall adoption rate of 10.7% (p < 0.001). In the subset eligible for fractionation (5, 15–16, 25–28 fractions; N = 31,448), 5-fraction RT accounted for 11.7% and differed significantly by insurance type (p < 0.001): Medicare 17.4%, Private 7.6%, Medicaid 5.9%, and Uninsured 6.9%. Geographic variation was notable (p < 0.001), ranging from 7.3% in mid-size metropolitan areas (250,000–1 million population) to 17.7%–18.1% in more remote or non-adjacent areas; large metropolitan areas (≥1 million) had 12.8% uptake. Neighborhood income showed a gradient (p < 0.001): 10.1% in the lowest quartile compared to 12.5% in the highest. Race was also associated with uptake (p < 0.001), with lower use among Black patients compared to White patients (9.4% vs 12.2%). Conclusions: In routine U.S. practice, adoption of 5-fraction breast RT increased rapidly from 2020 to 2023, with the most pronounced growth after 2021, reflecting the swift translation of trial evidence into clinical practice. However, uptake varies by insurance, geography, income, and race, indicating that diffusion is not uniform. Given the potential benefits of ultra-hypofractionation in reducing treatment burden and supporting timely completion, targeted implementation strategies, such as provider education, reimbursement alignment, and facility-level operational support, may be necessary to ensure equitable access as 5-fraction regimens become more widely adopted and potentially become the standard of care.

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.

e20012 Background: PM 2.5, particulate matter with a diameter of 2.5 micrometers or less, is a major contributor to lung cancer and associated mortality. Epidemiological studies reveal a concerning trend, with each 10 micrograms per cubic meter increase in PM 2.5 associated with a 15% higher risk of lung cancer and a 13% increase in mortality rates, underscoring the significant burden it imposes on public health systems globally. We aimed to evaluate the odds of association between environmental exposure to PM 2.5 and the risk of lung cancer and associated mortality. Methods: We performed a systematic review and umbrella meta-analysis using studies containing quantitative data on PM 2.5 and lung cancer. We used PRISMA guidelines and the MOOSE protocol using PubMed and MeSH terms like PM 2.5, non-small cell cancer, lung cancer, pollutants, particulate matter 2.5, and environmental factors. We had excluded non-full-length articles, non-meta-analysis studies, and non-human studies. RavMan 5.4 was used, and generic inverse variance methods with mixed effect models were applied to identify a pooled risk ratio with a 95% confidence interval. Forest plots were obtained, and sensitivity analysis was performed based on funnel plots and I2 (heterogeneity) values. Results: Of the 245,529 articles evaluated for the quality of the data, 99 met the inclusion and exclusion criteria. Out of 99, we used six articles to derive the quantitative data. In umbrella meta-analysis, PM 2.5 exposure was associated with a 1.16 times higher risk (95%CI: 1.1-1.22, p<0.00001, I2=0%) of lung cancer and a 1.22 times higher risk of non-lung cancers (95%CI: 1.15-1.30, p<0.00001, I2=0%). PM 2.5 was associated with non-significant higher mortality (RR: 1.06, 95%CI: 0.99-1.13, p=0.09, I2=97%) with leave-on-out analysis (excluding Chen et al.) significant association between mortality and PM 2.5 (RR: 1.08, 95%CI: 1.06-1.10, p<0.00001, I2=0%). Conclusions: Our umbrella meta-analysis shows a significant risk of lung cancer and mortality from PM 2.5 exposure. Further investigation and increased consciousness are necessary to mitigate the risk of lung cancer associated with this pollutant.