Mal, Madho

e23089 Background: Sodium–glucose cotransporter-2 (SGLT2) inhibitors are increasingly used for glycemic and cardiovascular benefits; however, concerns persist regarding genitourinary infections, particularly in vulnerable populations such as patients with cancer and diabetes. Real-world data evaluating the safety of SGLT2 inhibitors in this population remain limited. We evaluated the association between SGLT2 inhibitor use and genitourinary infection risk among cancer patients with type 2 diabetes. Methods: We conducted a retrospective cohort study using the TriNetX federated research network. Adult patients (≥18 years) with malignant neoplasms and type 2 diabetes mellitus were identified. Patients were stratified based on exposure to SGLT2 inhibitors and compared with cancer patients with diabetes not receiving SGLT2 inhibitors. Primary outcomes included urinary tract infection (UTI) and cystitis, identified using ICD-10 diagnostic codes. Analyses included unadjusted comparisons, 1:1 propensity score matching (PSM), and a Cox proportional hazards model as a sensitivity analysis to assess time to first UTI within one year following index exposure. Results: A total of 7,485 patients were included (7,137 without SGLT2 inhibitors and 348 with SGLT2 inhibitors). In unadjusted analyses, crude rates of UTI and cystitis were numerically higher in the SGLT2 inhibitor cohort. After 1:1 propensity score matching (312 patients per cohort), baseline characteristics were well balanced. The incidence of UTI was identical between matched cohorts (6.41% vs 6.41%, p = 1.00), with no significant differences observed for cystitis or acute cystitis. In a Cox proportional hazards sensitivity analysis, SGLT2 inhibitor use was associated with a significantly lower hazard of UTI compared with no SGLT2 inhibitor exposure (hazard ratio 0.68, 95% confidence interval 0.52–0.89; p = 0.0048). Conclusions: In this large real-world cohort of cancer patients with diabetes, SGLT2 inhibitor use was not associated with an increased risk of genitourinary infections. Propensity-matched analyses demonstrated no difference in absolute infection risk, while time-to-event analysis suggested a lower hazard of UTI among patients receiving SGLT2 inhibitors. These findings support the genitourinary safety of SGLT2 inhibitors in cancer patients with diabetes and may inform clinical decision-making in this high risk population.

e22604 Background: Heart, pericardial, and mediastinal tumors are rare neoplasms with potential sex-specific disparities. Despite their clinical significance, long-term temporal trends stratified by sex remain poorly characterized. Methods: We conducted a population-based analysis using data from the Surveillance, Epidemiology, and End Results (SEER) database, evaluating annual case counts from 1975 to 2022, stratified by sex. Temporal trends in total, male, and female cases were assessed using linear regression models. Results: A total of 657 cases were reported over the study period (445 males; 212 females). Total case counts showed a significant upward trend, increasing by 1.25 cases per year (p < 0.001, R² = 0.59). Male cases increased by 0.85 cases/year (p < 0.001), nearly twice the increase observed in females (0.40 cases/year, p < 0.001). Male predominance persisted throughout the study period, with both sexes showing a gradual upward trend, reflecting a consistent sex disparity in these tumors. Conclusions: The occurrence of heart, pericardial, and mediastinal tumors has increased steadily over the past five decades, disproportionately affecting males. These findings highlight persistent sex-based disparities and underscore the need for further sex-specific research to elucidate underlying risk factors and inform targeted surveillance and early detection strategies.

e22593 Background: Pheochromocytoma is a rare neuroendocrine tumor, and population-level data describing long-term temporal trends are limited. Evaluating national patterns over time may improve epidemiologic understanding and clinical awareness. Methods: We performed a retrospective analysis of pheochromocytoma cases recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 through 2022. Annual case counts were examined overall and by race (White, Black, Other, and Unknown). Temporal trends were assessed using Poisson regression, and annual percent change (APC) was calculated to quantify changes over time. Results: A total of 408 pheochromocytoma cases were identified during the study period. Overall case counts increased significantly over time, with Poisson regression demonstrating a consistent upward trend corresponding to an APC of 5.8% per year (p < 0.001). White individuals accounted for the majority of reported cases, while Black and other racial groups had significantly lower case counts compared with the reference population. Visual assessment of decade-level trends suggested a gradual increase from 1975 through approximately 2010, followed by a sharper rise in more recent years. Conclusions: Pheochromocytoma case counts in the United States have increased substantially over the past five decades based on SEER data. These findings suggest evolving epidemiologic patterns in this rare tumor and emphasize the importance of continued surveillance. Observed trends should be interpreted in the context of potential changes in diagnostic practices, imaging utilization, and cancer registry reporting over time.

e19562 Background: Multiple myeloma is a chronic blood cancer in which patients often live for many years, yet the risk of death remains ongoing. While survival has improved over time, population-level studies that combine traditional survival analysis, advanced modeling techniques, and future burden projections are limited. Methods: We performed a population-based retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. Parametric survival modeling was conducted using Weibull regression to better characterize long-term mortality patterns. Machine-learning survival analysis was performed using random survival forests to assess the relative importance of clinical and demographic factors. Annual case counts were analyzed and projected through 2035 using time-series forecasting methods. Results: The study included 8,627 patients with multiple myeloma. Overall survival declined gradually over long-term follow-up, with approximately one-quarter to one-third of patients surviving at extended time points. Female patients experienced better survival than males. Significant survival differences were observed across racial groups, with Asian or Pacific Islander patients demonstrating the most favorable outcomes and American Indian or Alaska Native patients the poorest. In multivariable analyses, age, sex, race, and year of diagnosis were independently associated with survival. Parametric modeling closely mirrored non-parametric survival estimates and supported a time-dependent pattern of mortality. Machine-learning analysis identified year of diagnosis as the strongest predictor of survival, followed by age and race. Forecasting suggested that the burden of multiple myeloma will remain substantial through 2035. Conclusions: Multiple myeloma is associated with long-term survival but persistent mortality risk and ongoing demographic disparities. Combining traditional survival analysis with parametric and machine-learning approaches provides a more complete understanding of outcomes and highlights the sustained future burden of this disease, with important implications for clinical care and healthcare planning.

e18624 Background: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients with hematologic malignancies. Although meta-analyses identify systemic corticosteroid exposure as a strong relative risk factor for IFI, the absolute burden attributable to corticosteroids across heterogeneous baseline risk settings remains poorly defined. We applied meta-analysis-based projection modeling to translate relative risk estimates into absolute, population-level IFI outcomes. Methods: Using pooled odds ratios for IFI associated with systemic corticosteroid exposure from a published meta-analysis (OR 2.84; 95% CI 1.42–5.70), we projected IFI incidence under a proportional odds framework. The primary analysis assumed a baseline IFI incidence of 15% in patients not receiving corticosteroids, with sensitivity analyses conducted across baseline incidences ranging from 10% to 25%. IFI-related mortality was estimated using a case-fatality rate of 45%. Outcomes were expressed as projected IFI incidence, excess IFIs and IFI-attributable deaths per 1,000 patients, population attributable fractions, and one-way sensitivity analyses. Results: At a baseline IFI incidence of 15%, systemic corticosteroid exposure increased projected IFI incidence to approximately 34%, corresponding to an excess of ~190 IFIs per 1,000 patients. This translated into approximately 80 excess IFI-attributable deaths per 1,000 patients, with a plausible range of 25–160 based on uncertainty in the pooled effect estimate. Sensitivity analyses demonstrated a monotonic increase in projected IFI incidence with rising baseline risk, with corticosteroid-associated IFI incidence approaching 50% at higher baseline levels. Population-attributable fraction modeling indicated that when corticosteroid use prevalence exceeded 40%, nearly half of IFIs in the population were attributable to corticosteroid exposure. One-way sensitivity analyses identified the corticosteroid effect size as the dominant driver of excess IFI mortality, exceeding the influence of baseline incidence or IFI case-fatality assumptions. Conclusions: Projection modeling based on meta-analytic risk estimates demonstrates that systemic corticosteroid exposure is associated with a substantial and clinically meaningful absolute increase in IFIs and IFI-related mortality. Translating relative risk estimates into absolute population-level outcomes highlights the potential magnitude of preventable infectious harm associated with corticosteroid use and provides actionable insight to inform risk-mitigation strategies in high-risk hematologic populations.

e18602 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of hematologic malignancies but is frequently complicated by cytokine release syndrome (CRS) and immune-mediated neurotoxicity (NS). As CAR-T programs expand, population-level projections of treatment-related toxicities are essential for program planning and risk mitigation, yet remain poorly characterized. Methods: We performed a cohort-based forecasting analysis using pooled incidence rates of CRS and NS derived from published meta-analyses of CAR-T clinical trials. Expected numbers of toxicity events were projected for hypothetical cohorts of 100, 500, and 1,000 CAR-T–treated patients. Uncertainty was quantified using binomial 95% confidence intervals. Disease-specific projections were generated by applying stratified pooled toxicity rates for hematologic malignancies and solid tumors. Results: For a projected cohort of 1,000 CAR-T–treated patients, forecasts estimated approximately 770 patients would experience CRS of any grade, 290 would develop grade ≥3 CRS, 400 would experience NS of any grade, and 280 would develop grade ≥3 NS. Toxicity counts increased proportionally with cohort size and demonstrated predictable uncertainty bounds. When stratified by disease type, hematologic malignancies exhibited substantially higher toxicity burdens than solid tumors across all endpoints. At a cohort size of 1,000 patients, hematologic malignancies were associated with markedly higher rates of both CRS and severe neurotoxicity, whereas solid tumors demonstrated consistently lower toxicity burdens. Conclusions: Using pooled clinical trial data, this forecasting model provides quantitative estimates of CAR-T–associated toxicity burdens at the population level. Severe CRS and neurotoxicity remain common and scale predictably with program size, particularly in hematologic malignancies. These findings offer a pragmatic framework for anticipating resource utilization, toxicity management needs, and safety planning as CAR-T therapy continues to expand.

e18542 Background: Outcomes in adult acute lymphocytic leukemia (ALL) remain heterogeneous and strongly influenced by age. However, population-level survival gradients across older age strata and the future burden of disease in an aging population remain incompletely characterized. We evaluated long-term survival patterns and projected disease burden in adult ALL using national registry data. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database including adults aged 50–89 years diagnosed with ALL between 2000 and 2022. Overall survival (OS) was estimated using Kaplan–Meier methods and compared across age and racial subgroups. Multivariable Cox proportional hazards regression was performed to identify independent predictors of mortality. Temporal trends in annual case counts were analyzed and projected through 2035 using time-series forecasting methods. Results: A total of 7,298 adult ALL patients were included. OS declined progressively with advancing age, demonstrating clear stepwise separation across age strata. Compared with patients aged 50–54 years, mortality risk increased incrementally across successive age groups, reaching more than fourfold higher risk among patients aged 85–89 years on multivariable analysis. Race-based survival differences were observed on unadjusted analysis; however, these differences were attenuated after adjustment for age and clinical factors. More recent year of diagnosis was independently associated with modest survival improvement, reflecting incremental therapeutic progress. Forecasting analysis projected a continued rise in adult ALL case burden through 2035, with widening uncertainty intervals over time, indicating sustained future healthcare impact. Conclusions: Adult ALL outcomes remain strongly age dependent, with sharply escalating mortality risk among older patients despite gradual therapeutic improvements. Projections indicate a sustained and growing disease burden in the United States. These findings highlight the urgent need for age-adapted treatment strategies, improved inclusion of older adults in clinical trials, and healthcare system preparedness to address the needs of an aging leukemia population.

e18536 Background: Nucleophosmin 1 (NPM1) mutation is traditionally associated with a favorable prognosis in acute myeloid leukemia (AML), leading to classification of these patients within the European LeukemiaNet (ELN) favorable risk group. However, emerging evidence indicates that co-occurring secondary-type mutations (STMs), including ASXL1 , RUNX1 , EZH2 , and SRSF2 , may substantially modify this prognosis. While meta-analyses have quantified the relative risk associated with STMs using hazard ratios, the corresponding absolute survival impact remains unclear, limiting clinical interpretability and decision-making. Methods: We performed meta-analysis–based projection modeling using pooled overall survival hazard ratios reported in a recent systematic review and meta-analysis of 4,022 NPM1-mutated AML patients. For the ELN-favorable subgroup, the pooled hazard ratio for overall survival associated with STMs (HR 1.95; 95% CI 1.39–2.73) was combined with externally derived baseline 5-year survival estimates under a proportional hazards framework. Absolute survival probabilities were calculated using established survival–hazard transformations, and results were translated into projected outcomes for a hypothetical cohort of 1,000 future ELN-favorable NPM1-mutated AML patients. Uncertainty was quantified using the meta-analytic confidence interval. Results: Assuming a baseline 5-year overall survival of 70% for ELN-favorable NPM1-mutated AML patients without STMs, the presence of STMs was projected to reduce 5-year survival to approximately 50%. Based on the confidence interval of the pooled hazard ratio, projected survival with STMs ranged from 38% to 61%. In a simulated cohort of 1,000 patients, this corresponds to approximately 300 deaths at 5 years in the absence of STMs versus 501 deaths in the presence of STMs, yielding an estimated 200 excess deaths per 1,000 patients (plausible range: 90–320 excess deaths). These findings were robust across visualizations including absolute survival projections, stacked outcome distributions, and excess mortality estimates. Conclusions: Meta-analysis–based projection modeling demonstrates that secondary-type mutations may negate much of the favorable prognosis traditionally attributed to ELN-favorable NPM1-mutated AML, translating into a large absolute survival decrement in future patient cohorts. Converting relative risk estimates into absolute survival and event projections provides clinically actionable insight and supports the incorporation of secondary-type mutation status into risk stratification, trial design, and therapeutic decision-making.

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.