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Abstract Background: Patients with myelodysplastic syndromes (MDS) are highly susceptible to infections, with sepsis being a major cause of hospitalization and death. While gender differences in sepsis outcomes have been described in broader populations, their impact among patients with MDS remains poorly defined. Methods: We performed a retrospective cohort study using the National Inpatient Sample (NIS) from 2016 to 2022 to identify adult hospitalizations with co-diagnoses of MDS and sepsis. Patients were stratified by sex: male (n = 47,170) and female (n = 31,365). Multivariable logistic regression was used to evaluate the association between female sex and key outcomes: respiratory failure, encephalopathy, disseminated intravascular coagulation (DIC), Clostridioides difficile infection (CDI), fungal sepsis, and in-hospital mortality. Models were adjusted for demographics, comorbidities, and hospital characteristics. Results: Female sex was independently associated with increased odds of respiratory failure (OR 1.05, 95% CI 1.01–1.08, p = 0.011) and encephalopathy (OR 1.07, 95% CI 1.02–1.12, p = 0.010). There was a nonsignificant trend toward higher odds of CDI (OR 1.14, p = 0.086). No significant sex-based differences were observed for DIC (OR 0.84, p = 0.103), fungal sepsis (OR 0.89, p = 0.598), or in-hospital mortality (OR 0.98, p = 0.653). Conclusion: In this large national analysis of MDS patients hospitalized with sepsis, female patients were more likely to experience respiratory failure and encephalopathy, but sex was not significantly associated with mortality, DIC, or fungal infections. These findings suggest that while certain complications may differ by sex, overall in-hospital survival remains comparable between male and female patients with MDS and sepsis.Keywords: Myelodysplastic syndromes, sepsis, gender disparities, mortality, respiratory failure, encephalopathy, NIS

Following lung cancer, prostate cancer is the leading cause of cancer death in men. High-risk localized tumor burden or metastatic disease often progresses, refractory to initial treatment regimens. There is ongoing development of technology to appropriately identify high-risk patients, stage them correctly, and offer appropriate treatments to obtain the best clinical outcomes. Prostate cancer-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase, which helps regulate folate absorption, and its overexpression is pathologically directly proportional and associated with prostate cancer. Increased PSMA expression is a known independent risk factor for poorer survival, and most metastatic lesions in CRPC are PSMA positive. Over the last decade, several PSMA-based PET radiopharmaceuticals have demonstrated superior sensitivities and specificities compared to traditional imaging methods. These outcomes have been demonstrated by several large clinical trials. As the data emerges, these diagnostics are being integrated into standard of care protocol to facilitate nuanced identification of malignant lesions. PSMA is also being targeted through several therapeutics, including radioligands and immunotherapies such as CAR-T, BiTEs, and ADCs. This review will discuss the landscape of PSMA-based theranostics in the context of prostate cancer.

e13154 Background: Triple-negative breast cancer (TNBC) is a less common but highly aggressive subtype of breast cancer with poor prognosis and limited therapeutic options. Despite advancements in oncology, significant survival disparities persist among racial, histologic, and socio-demographic groups. This study investigates these disparities and identifies factors contributing to unequal outcomes, providing actionable insights for improving care. Methods: Data on TNBC cases from 2000 to 2021 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, encompassing 17 registries and 76,265 patients. Patients were categorized by stage, marital status, age, race, and histology. Kaplan-Meier survival analysis was used to estimate median survival with 95% confidence intervals (CI), and the log-rank test assessed differences across groups. Cox proportional hazards regression determined the magnitude of disparities. A p-value < 0.05 was considered statistically significant. Results: Among the 76,265 patients analyzed, those with distant-stage disease had the poorest median survival (51 months; 95% CI: 46–60), compared to localized-stage patients (128 months; 95% CI: 127–129). The youngest cohort (15–19 years) exhibited the lowest survival (43 months), while individuals aged 80–84 had a median survival of 79 months (95% CI: 76–84). South Asians, particularly Pakistani individuals, had the shortest survival among racial groups (83 months). Single patients had lower survival (116 months) compared to married or divorced individuals. Histologically, median survival was 113 months (95% CI: 103–120) for epithelial neoplasms and 78 months for mucoepidermoid neoplasms. All observed differences were statistically significant (p < 0.05). Conclusions: Localized-stage TNBC, individuals aged 40–44, and patients from White or Black racial groups exhibited better survival outcomes, as did those with cystic, mucinous, or serous histologies compared to epithelial neoplasms. Addressing these disparities through tailored treatment strategies and improved access to care is critical. Limitations of this study include the lack of treatment-level data and the potential influence of unmeasured confounders. Stage Marital Status Age Group at Diagnosis Distant Localized Single Divorced 15-19 40-44 80-84 Median Survival(LCL-UCL) 51(46-60) 128(127-129) 116(114-118) 127(124-129) 43(14-NA) 132(130-135) 79(76-84) Neoplasm Histology Race Epithelial Muco-epidermoid Cystic, Mucinous& Serous Pakistani OtherAsian Black White Median Survival(LCL-UCL) 113 (103-120) 78(63-NA) 142(123-NA) 83 (63-NA) 97(91-108) 123 (121-125) 126 (125-127) LCL= Lower Confidence Limit, UCL= Upper Confidence Limit.

5108 Background: We previously proposed a hybrid framework combining LLMs and rule based algorithm (RBA) for automating risk stratification in locPCa. Herein, we aim to validate the risk stratification agent (RSA) in a prospective cohort, develop & evaluate the treatment recommendation agent (TRA) based on NCCN guidelines, and develop an interactive interface to facilitate clinicians for accurate risk stratification and treatment recommendations at the point of care. Methods: This study included pts with locPCa (2004-2024) presenting at Mayo Clinic with at least 1 positive prostate biopsy and MRI report available. For RSA prospective validation, GPT4 extracted key phenotypic variables (PSA, T stage, prostate volume, number of cores, Gleason patterns, grade group) from unstructured MRI and biopsy reports using a zeroshot prompt. An RBA then classified pts into NCCN risk groups. The agent performance was compared with the treating clinician's documentation and evaluated against gold-standard labels manually annotated by two independent clinicians. For development of TRA, two experiments were performed using GPT4 with and without retrieval-augmented generation (RAG) to generate treatment plans. Generated treatment plans were evaluated using NCCN guideline-informed treatment decision tree based algorithm (DTA). Evaluation metrics, weighted – accuracy (acc) and F1, were computed. A clinician facing interface (lisr.org/risk) was developed to provide accurate risk stratification and treatment plans. Results: A total of 858 pts were included (500 for prospective validation, 358 for treatment recommendations). Prospective validation for RSA demonstrated a higher F1 score of 0.89 compared to the treating clinician (F1: 0.58). Treatment recommendation experiments showed that GPT4 with RAG achieved higher acc (64% full – all correct treatment options and 36% partial – at least 1 correct treatment option) compared to GPT4 alone (35% and 65%, respectively). Sensitivity analysis using DTA-informed GPT4 note generation achieved 94% full acc and 6% partial acc. GPT4 alone generated hallucinated treatment options in 71% of cases, while GPT4 with RAG reduced this to 32%. Conclusions: The multi-agent framework based on LLM and RBA achieves high accuracy in risk stratification and treatment recommendation for locPCa. A multi-agent framework with an interactive interface holds high promise to enable efficient, accurate decision-making, and improve locPCa management at the point of care Performance evaluation. RSA(acc; F1) % TRA(full acc; partial acc) % Clinician RSA* GPT4 RAG+GPT4 DTA+GPT4 Overall 60; 58 89; 89 29; 71 64; 36 94; 6 V. High 94; 33 96; 96 55; 45 69; 31 93; 7 High 46; 52 92; 89 - - - Int. Unf 80; 61 91; 90 5; 95 38; 62 93; 7 Int. Fav 57; 64 84; 87 0; 100 98; 2 100; 0 Low 57; 65 87; 80 100; 0 95; 5 90; 10 V. Low 8; 13 50; 67^ - - - *Statistical significance (p<0.01) except for ^V. Low.

e17155 Background: Localized PCa is classified into six NCCN risk categories, each with specific treatment recommendations. However, treatment concordance across these categories and its variation by race in clinical practice remain unexplored. Therefore, we aim to describe patterns of guideline-concordant treatment receipt for localized PCa across risk groups and race. Methods: Surveillance, Epidemiology, and End Results (SEER) database (2018–2020) was queried to identify patients with localized PCa from 17 registries. Data regarding clinical T stage, Gleason patterns, PSA level, biopsy cores and initial treatment received (radiation, radical prostatectomy, systemic therapy) was obtained. Each patient was then stratified into one of six NCCN-based risk categories using a rule-based algorithm. Using the stratified risk category of each patient, treatment recommendations were obtained from the NCCN guidelines. Concordance was assessed by comparing the received treatment and guideline-recommended treatment. A focused bi-variate logistic regression analysis was performed adjusting for risk groups, and race. Odds ratio (OR) with 95% confidence intervals (CI) were computed to quantify the magnitude of guideline-discordant treatment receipt. Results: This analysis included 69,584 patients with localized PCa (White: 53,875 [77.4%]; Black: 11,265 [16.2%]; Asian/Pacific Islander: 4,133 [5.9%]; American Indian/Alaska Native: 311 0.5%]). In terms of risk groups, patients in higher risk categories had increased odds of discordance compared to the lower risk groups (Table). In terms of race, Black men had significantly higher odds of receiving guideline-discordant therapy (OR:1.67, 95% CI:1.58–1.76), while no statistically significant difference was observed with American Indian/Alaska Native men (OR:1.21, 95% CI: 0.92–1.61) and Asian/Pacific Islander men (OR:1.05, 95% CI:0.97–1.14) compared to White men. Conclusions: Population level data, based on limited sample size in some groups, suggests that treatment concordance with NCCN guidelines varies by risk group and race in localized PCa. Black patients, and those with higher risk groups were more likely to receive guideline-discordant therapy. These findings highlight the need for strategies and prospective studies at individual patient level to evaluate and enhance guideline adherence to promote personalized care for these patients. Variable Discordant Treatment (%) OR (95% CI) White 22168 (41.1) REF Black 5653 (47.5) 1.67 (1.58-1.76) * Asian/Pacific Islander 1822 (44.1) 1.05 (0.97-1.14) American Indian/Alaska Native 191 (61.4) 1.22 (0.92- 1.61) Very Low Risk 770 (9) REF Low Risk 146 (2) 0.16 (0.13-0.19) * Favorable Risk 35 (0.4) 0.03 (0.02-0.04) * Unfavorable Risk 15125 (83.2) 36.30 (33.72-39.25) * High/Very High Risk 13441 (50) 7.32 (6.83-7.86) * * p <0.05.

e23101 Background: Liver cell carcinoma (LCC) and hepatic failure (HF) are major contributors to global adult mortality. Identifying trends and disparities in LCC and HF-related deaths is critical for addressing public health challenges and guiding prevention strategies. This study examines national trends in LCC and HF-related mortality from 1999 to 2023, with an emphasis on demographic, geographic, and temporal disparities in age-adjusted mortality rates (AAMRs). Methods: Using the CDC WONDER database (1999–2023), this descriptive study identified deaths attributed to LCC (ICD-10 code C22.0) and HF (ICD-10 code K72.9) among adults aged 25 and older. Mortality data were stratified by gender, race/ethnicity, census region, urban-rural classification, and state. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals were calculated, and trends were analyzed using Joinpoint regression to determine annual percent changes (APCs) with 95% confidence intervals (CIs). Statistical significance was set at p < 0.05, and the study followed STROBE guidelines. Results: From 1999 to 2023, there were 22,963 deaths attributed to LCC and HF (Men: 17,822; Women: 5,141). Overall, AAMRs declined from 1999 to 2007 (APC: -2.4), stabilized between 2007 and 2017 (APC: 0.2), and declined again from 2017 to 2023 (APC: -3.5). Men experienced a steady AAMR decline from 1999 to 2010 (APC: -2.1), followed by stabilization (2010–2017, APC: 0.7), and further decline (2017–2023, APC: -4.4). Women showed a sharp AAMR decrease from 1999 to 2006 (APC: -3.8) and a relatively stable trend thereafter (APC: -0.1). Non-Hispanic Blacks people experienced an overall AAMR decline from 1999 to 2020 (APC: -0.9). Among Non-Hispanic Whites people, AAMRs decreased initially (1999–2006, APC: -2.6), rose slightly (2006–2018, APC: 0.5), and declined further (2018–2020, APC: -7.3). Regional AAMRs varied, with the West having the highest overall AAMR (5.6; 95% CI: 5.4–5.7) and the Midwest the lowest (3.2; 95% CI: 3.1–3.3). Hawaii reported the highest state AAMR (10.3; 95% CI: 8.9–11.6), while Arkansas had the lowest (2.4; 95% CI: 2.0–2.9). Urban-rural disparities revealed a sharper AAMR decline in metropolitan areas (1999–2005, APC: -3.9) and the non-metropolitan areas showed a slight increase (1999–2020, APC: 1.3). Conclusions: LCC and HF-related mortality rates have shown significant declines over the past two decades, with variations across gender, race, and geographic locations. Men and urban populations experienced steeper reductions in AAMRs, while rural populations exhibited slower improvements or slight increases in mortality. These findings highlight the need for targeted public health interventions to address disparities and further reduce LCC and HF-related mortality in vulnerable populations.

e16157 Background: The optimal treatment for resectable gastric/GEJ AC is unclear due to limited direct comparisons among chemotherapy and chemoradiation regimens. Addressing this gap is critical to improve patient outcomes. We performed this network meta-analysis (NMA) to determine the relative efficacy of multimodality regimens for resectable gastric/GEJ AC. Methods: MEDLINE, EMBASE, Scopus, and CENTRAL were searched from inception till September 20, 2024, to identify phase III trials evaluating perioperative/neoadjuvant systemic therapy ± radiation in resectable gastric/GEJ AC. Primary outcomes were disease-free survival (DFS) and overall survival (OS). A frequentist NMA was conducted to compare hazard ratios (HR) and 95% CI for each outcome. Relative treatment rankings were assessed using P-scores. Results: Fifteen trials (8,072 patients) were analyzed. pFLOT (perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel) ranked highest for DFS in the overall population (P score 91%) (Table), significantly outperforming surgery alone (HR 0.48, 95% CI 0.38-0.60) and nCROSS (neoadjuvant paclitaxel, carboplatin and radiotherapy) (0.67, 0.56-0.81). For OS, nPLF+nCRT(EP) (neoadjuvant cisplatin, leucovorin and fluorouracil for induction, followed by etoposide, cisplatin, and radiotherapy) (P score 90%) and pFLOT (P score 87%) were the top regimens, with pFLOT significantly outperforming surgery alone (0.57, 0.45-0.72), and nCROSS (0.73, 0.60-0.89). Adding neoadjuvant chemoradiation to pFLOT provided no additional OS (1.14, 0.76-1.72) or DFS (1.22, 0.83-1.82) benefit. Similarly, adding pembrolizumab to perioperative chemotherapy (CF/CX) (cisplatin and fluorouracil/capecitabine) was not superior to pFLOT in terms of DFS (1.10, 0.71-1.69) or OS (1.09, 0.69-1.72). Conclusions: pFLOT demonstrated superior efficacy in resectable gastric/GEJ AC, surpassing surgery alone, nCROSS, and other perioperative regimens. The additive role of immunotherapy to pFLOT requires further investigation to refine patient selection and optimize outcomes. Regimen Overall Population GEJ cohort OS DFS OS DFS nPLF+nCRT(EP) 1 (90) 2 (84) 1 (85) NA pFLOT 2 (87) 1 (91) 2 (79) 2 (88) pPembrolizumab+CF/CX 3 (75) 3 (81) 5 (41) - nECX 4 (61) 5 (55) - - pCF 5 (59) 8 (51) 3 (72) - pECF/ECX 6 (47) 6 (55) 7 (40) 3 (57) nECX+aCRT(CX) 7 (45) 7 (52) 9 (31) - nCF 8 (42) 10 (28) 6 (40) - nCROSS 9 (41) 9 (35) 8 (34) 4 (43) pECF/ECX/FLOT+nCRT(F/X) 10 (38) 4 (57) 4 (72) 1 (90) nCRT(CF) 11 (9) 11 (6) - 5 (14) Surgery 12 (7) 12 (5) 10 (5) 6 (9) Data reported as rank (P-score). Abbreviations: n: neoadjuvant; p: perioperative; ECX: epirubicin + cisplatin + capecitabine; CF: cisplatin + fluorouracil; ECF: epirubicin + cisplatin + fluorouracil; aCRT(CX): adjuvant radiotherapy + cisplatin + capecitabine; CRT(F/X): fluorouracil/capecitabine + radiotherapy; CRT(CF): cisplatin + fluorouracil + radiotherapy.

e16418 Background: Pancreatic cancer remains one of the most fatal malignancies globally, posing a significant burden on older populations. Despite numerous reports on its prevalence, a detailed comparative analysis of national trends among adults aged 70 and older from 1990 to 2021 is scarce. This study seeks to bridge this gap by evaluating prevalence rates using data from the Global Burden of Disease (GBD) study. Methods: Prevalence data for pancreatic cancer in individuals aged 70 years and older were obtained from the GBD-2021 dataset, encompassing 204 countries and territories for the years 1990 and 2021. The Estimated Annual Percent Change (EAPC) and corresponding 95% confidence intervals (CI) were calculated to assess trends over the period from 1990 to 2021. Results: The prevalence of pancreatic cancer has shown a significant increase since 1990, reaching its highest levels in 2021. In 1990, the United States of America (USA) reported the highest prevalence, followed by Japan and China. However, by 2021, Japan ranked first in prevalence, followed by China and the USA. The analysis revealed that in 1990, the highest prevalence rates of pancreatic cancer were observed in Greenland (91.04 per 100,000), followed by Finland (82.57 per 100,000) and Japan (76.30 per 100,000). By 2021, Japan reported the highest prevalence (126.73 per 100,000), followed by Finland (119.20 per 100,000) and Canada (109.22 per 100,000). Despite the observed prevalence rates from 1990 to 2021, Turkmenistan exhibited the most significant increase (EAPC: 15.41, 95% CI: 10.91, 21.41), followed by the Republic of Cabo Verde (EAPC: 13.61, 95% CI: 8.67, 19.59) and Mongolia (EAPC: 4.81, 95% CI: 3.11, 7.20). In contrast, the most significant declines were recorded in the Republic of San Marino (EAPC: -0.308, 95% CI: -0.51, -0.03), followed by Guam (EAPC: -0.24, 95% CI: -0.37, -0.08) and Cuba (EAPC: -0.21, 95% CI: -0.33, -0.09). Conclusions: The prevalence of pancreatic cancer among adults aged 70 and older has increased significantly over the past three decades, with distinct regional patterns. Countries like Japan, China, and the USA continue to report the highest prevalence rates. These findings highlight the urgent need for targeted prevention, screening, and treatment strategies, particularly in high-burden regions, to mitigate the growing impact of pancreatic cancer in aging populations. Prevalence percent changes. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) Highest prevalence percent change Turkmenistan 0.62 10.16 15.41 (10.91, 21.41) Republic of Cabo Verde 3.23 47.18 13.61 (8.67, 19.59) Mongolia 5.25 30.53 4.81 (3.11, 7.20) Lowest prevalence percent change Republic of San Marino 52.61 36.36 -0.308 (-0.51, -0.03) Guam 16.96 12.87 -0.24 (-0.37, -0.08) Cuba 32.65 25.52 -0.21 (-0.33, -0.09)

e22572 Background: Pancreatic cancer is a highly lethal malignancy that disproportionately impacts older populations, contributing significantly to global disease burden. Disability-adjusted life years (DALY) serve as a comprehensive metric to quantify the combined impact of mortality and morbidity. This analysis of the Global Burden of Disease Study-2021 (GBD-2021) aims to characterize trends in DALY rates attributable to pancreatic cancer among individuals aged 70 years and older across 204 nations. Methods: Data on DALY associated with pancreatic cancer for individuals aged 70+ were extracted for 204 nations from the GBD-2021 study for the years 1990 and 2021. Estimated annual percent change (EAPC) with 95% confidence intervals (CI) were calculated from 1990 to 2021. Results: The DALY rates were accessed among individuals aged 75 and older diagnosed with pancreatic cancer. In 1990, Greenland exhibited the highest DALY rate globally (2825.65), but by 2021, this position was surpassed by the United Arab Emirates (2775.52), with Greenland declining to the second-highest rate (2082.43). On the other hand, Turkmenistan had the lowest DALY rates in 1990, but by 2021, Mozambique had taken this position, with Turkmenistan ranking 170th. Despite the observed DALY rates from 1990 to 2021, Turkmenistan experienced the highest change (EAPC: 15.23, 95% CI: 10.88–21.18), followed by the Republic of Cabo Verde (EAPC: 12.88, 95% CI: 8.14–18.75) and Mongolia (EAPC: 4.53, 95% CI: 2.90–6.88). A decrease in DALY was observed in over 24 nations, with the Republic of San Marino recording the largest decline (EAPC: -0.37, 95% CI: -0.55, -0.12), followed by Bermuda (EAPC: -0.26, 95% CI: -0.43, 0.03) and Greenland (EAPC: -0.26, 95% CI: -0.45, -0.009). Conclusions: From 1990 to 2021, DALY rates related to pancreatic cancer among individuals aged 70 and older rose worldwide, particularly in Turkmenistan, the Republic of Cabo Verde, and Mongolia. There is a pressing need for global adoption of screening programs to enable early detection and treatment of these cases. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) HIGHEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PERCENT CHANGE Turkmenistan 19.66 319.09 15.22 (10.88–21.18) Republic of Cabo Verde 98.12 1361.76 12.88 (8.14–18.75) Mongolia 172.14 952.05 4.53 (2.90–6.88) LOWEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PERCENT CHANGE Republic of San Marino 1323.96 834.01 -0.37 (-0.55, -0.12) Bermuda 1696.97 1249.11 -0.26 (-0.43, 0.03) Greenland 2825.66 2082.43 -0.26 (-0.45, -0.009)

Abstract Background Optimal treatment for resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma remains unclear due to limited head-to-head comparisons among chemotherapy and chemoradiation regimens. This network meta-analysis aimed to determine the relative efficacy of available multimodality treatment regimens in these patients. Methods MEDLINE, EMBASE, Scopus, Web of Science, and CENTRAL were searched till September 20, 2024. Phase 3 randomized trials evaluating perioperative/neoadjuvant systemic therapy ± radiation in resectable gastric/GEJ adenocarcinoma were included. Primary outcomes were disease-free survival (DFS) and overall survival (OS). Frequentist network meta-analysis was conducted to compare hazard ratios (HRs) and 95% confidence intervals (CIs). Results Fifteen trials (8072 patients) were analyzed. pFLOT (perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel) ranked highest for DFS in the overall population (P-score 91%), achieving significant improvements compared to surgery alone (HR 0.48, 95% CI, 0.38-0.60) and nCROSS (neoadjuvant paclitaxel, carboplatin, and radiotherapy) (0.67, 0.56-0.81). For OS, nPLF + nCRT(EP) (neoadjuvant cisplatin, leucovorin, and fluorouracil for induction, followed by etoposide, cisplatin, and radiotherapy) (P-score 90%) and pFLOT (P-score 87%) were the top regimens. pFLOT significantly outperformed surgery alone (0.57, 0.45-0.72) and nCROSS (0.73, 0.60-0.89). Based on the limited data available, adding neoadjuvant chemoradiation to pFLOT provided no additional OS (1.14, 0.76-1.72) or DFS (1.22, 0.83-1.82) benefit. Similarly, adding pembrolizumab to perioperative chemotherapy (cisplatin and fluorouracil/capecitabine) was not superior to pFLOT (DFS: 1.10, 0.71-1.69; OS: 1.09, 0.69-1.72). Conclusions pFLOT demonstrated superior efficacy in resectable gastric/GEJ adenocarcinoma, outperforming surgery alone, nCROSS, and alternative perioperative regimens. The additive role of immunotherapy requires further investigation to optimize patient selection and outcomes.