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Background: Gastric cancer remains one of the leading causes of death globally and a major health concern. This study aims to analyze gastric cancer-related mortality trends over 2 decades. Methods: The CDC WONDER database was used to analyze and stratify de-identified death certificates from 1999 to 2022 across the United States. Trends in age-adjusted mortality rates (AAMR) were assessed using the Joinpoint Regression Program to determine annual percentage changes. Results: Overall, AAMR decreased from 79.26 in 1999 to 44.81 in 2022. Men and older adults had the highest AAMRs. Non-Hispanic (NH) Black or African Americans had the highest AAMR, while NH Whites had the lowest. Geographically, the Northeast had the highest AAMR, and metropolitan areas had higher AAMRs than nonmetropolitan areas. Conclusion: Gastric carcinoma has a poor prognosis, and although the general trend is decreasing across all sociodemographic areas, further research is required for targeted interventions and health policies for high-risk populations.

With the first series of PRRX1 -rearranged tumors published in 2019, the spectrum of these so-called fibroblastic tumors has been expanded. Since then, several smaller case series have been published; however, our understanding of them continues to be quite limited given their rarity. We herein studied 18 additional cases, the largest series to date. Eighteen tumors present in 9 male, 8 female, and 1 nonbinary patient with a median age of 35 years (range: 11 to 70 y) and involved the neck (5), the chest region (4), thigh (3), back (1), shoulder (1), forehead (1), lower leg (1), axilla (1), and the parapharyngeal region (1). Clinical follow-up (9/18 tumors; 50%; median: 10 mo; range: 4 to 40 mo) showed consistent indolent behavior without local recurrences or distant metastases. On morphology, these tumors were characterized by well-circumscription and distinctive peripheral crescent-shaped vessels. They were composed of uniform spindle and round cells growing in short fascicles within often densely hyalinized collagen lacking significant mitotic activity, necrosis, or cytologic atypia. Immunohistochemically, about half of the tested tumors expressed focal to rarely diffuse S100 with occasional co-expression of SOX10. Interestingly, almost half of the tested cases also showed complete loss of RB expression. All but 1 tumor harbored a PRRX1::NCOA1 fusion, while 1 case harbored a novel PRRX1::EP300 fusion. We herein provide additional data on these exceptionally uncommon tumors, expand their molecular spectrum, and compare them to their close morphologic mimics to aid in accurate diagnosis and avoid confusion with potentially more aggressive neoplasms.

ABSTRACTVarious cutaneous adnexal neoplasms have been associated with gene fusions as the main driver of their histogenesis, most of which showed poroid or hidradenomatous differentiation or represented other tumors of sweat glands. Recently, we encountered two cases of primitive basaloid neoplasms of predominantly folliculogenic/pilosebaceous origin, both surprisingly harboring recurrent EWSR1 rearrangements. Both tumors presented in young patients of either sex (1 F; 17 years; 1 M; 37 years) and involved the dermis and subcutaneous tissue of the abdominal wall (case 1) and the buttock (case 2). Histologically, the tumors were composed of primitive, basaloid cells with areas of keratinization (case 1) or foci of sebaceous differentiation (case 2) and stained strongly with keratins, p40 (case 1) or p63 (case 2), while lacking significant CD99 expression in both cases. Case 1 harbored an EWSR1::FLI1 fusion while case 2 harbored an EWSR1::PBX3 fusion. Clinical follow‐up was available for case 2 and showed no evidence of disease at 15 months of follow‐up. Methylation profiling showed case 1 to cluster with cutaneous squamous cell carcinoma, while case 2 was independent but positioned close to salivary gland epithelial‐myoepithelial carcinoma. These findings expand on the histopathologic and molecular genetic features of basaloid tumors with apparent adnexal differentiation and raise awareness to carefully interpret and correlate molecular findings with morphology and immunophenotype to avoid misinterpretation as a mesenchymal neoplasm.

e20520 Background: Cancer and respiratory failure (RF) are amongst leading causes of mortality in adults. This study investigates national trends in age-adjusted mortality rates (AAMRs) for cancer and RF in the United States from 1999 to 2023, focusing on disparities by gender, race, region, and rural-urban residence to inform public health strategies. Methods: This descriptive study analyzed data from the CDC WONDER database, of adults aged 25 and older. Mortality data were identified using ICD-10 codes C00–C97 (cancer) and J96 (RF). AAMRs per 100,000 population were calculated and stratified by gender, race/ethnicity, census region, urban-rural classification, and state. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs). Statistical significance was set at p < 0.05. Results: From 1999 to 2023, total deaths of 1,263,368 attributed to cancer and RF (682,141 men, 581,227 women). AAMRs declined from 1999 to 2004 (APC = -1.5, 95% CI: -4.0 to -0.4), stabilized from 2004 to 2012 (APC = 0.8, 95% CI: 0.1 to 2.4), and increased from 2012 to 2023 (APC = 3.2, 95% CI: 2.9 to 3.8). Men experienced a greater initial decline (APC = -2.1, 1999–2004) but significant increases thereafter (APC = 3.0, 2012–2023), while women showed a slower decline followed by sharper increases (APC = 3.5, 2013–2023). Non-Hispanic Black populations initially declined (APC = -1.7, 1999–2003) but later increased significantly (APC = 3.0, 2014–2020). Hispanic/Latino populations declined (APC = -1.2, 1999–2009) before rising sharply (APC = 3.1, 2009–2020). American Indian or Alaska Native populations showed consistent increases (APC = 1.7, 1999–2020). Urban areas experienced initial declines (APC = -1.7, 1999–2004), followed by increases (APC = 2.4, 2011–2020). Non-metropolitan areas exhibited steeper increases (APC = 4.6, 2014–2020). Regionally, the West recorded the highest AAMR (24.0), followed by the Northeast (23.6), South (20.9), and Midwest (18.0). Mississippi had the highest state-level AAMR (36.3), while Wisconsin had the lowest (10.0). States in the top 90th percentile included Mississippi, Arkansas, and California, while Wisconsin, Minnesota, and Oregon were among the lowest. Conclusions: Cancer and RF mortality declined initially but have significantly increased in recent years. Disparities persist across gender, racial, and regional groups, underscoring the need for focused public health efforts and equitable resource distribution to address these trends.

e20593 Background: Tislelizumab, an anti-PD-1 antibody, is emerging as a promising immunotherapy agent and has demonstrated clinical benefit and acceptable tolerability in recent lung cancer trials. This study aims to assess the safety and efficacy of Tislelizumab, as monotherapy or combined with chemotherapy (Group 1), as a superior treatment alternative for lung cancer compared to standard chemotherapy (Group 2) in improving patient outcomes. Methods: Following PRISMA guidelines, a systematic search was conducted through MEDLINE, Embase, Scopus, Science Direct, Cochrane (CENTRAL), and ClinicalTrials.gov from inception to December 2024 to identify Randomized Control Trials (RCTs). Hazards ratio (HRs) and risk ratios (RRs) were generated, by employing a Random-effects model with a 95% confidence interval (CI). Statistical analysis was performed using RevMan 5.4, with statistical significance set at p<0.05. Our outcomes of interest were Progression Free Survival (PFS), Overall Survival (OS), Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of response (DOR), and treatment-related adverse Events. Results: A total of 6 RCTs involving 2107 patients were included for analysis. Pooled analysis demonstrated that Group 1 significantly improved PFS, OS, and DOR with HRs of 1.85 (95% CI: 1.71-1.99; p <0.00001, I² = 0%), 2.01 (95% CI: 1.75-2.29; p <0.00001, I² = 0%) and 2.14 (95% CI: 1.52-3.03; p <0.0001, I² = 39%), respectively. Group 1 has better DCR and ORR compared to Group 2 with RRs of 1.52 (95% CI: 1.12-2.07; p= 0.007, I² = 97%) and 1.50 (95% CI: 1.20-1.86; p= 0.0003, I² = 83%), respectively. The high heterogeneity observed in the pooled analysis of DCR (I² = 97%) and ORR (I² = 83%) likely reflects variability in study populations, treatment protocols, and response assessment criteria across the included RCTs. Subgroup or sensitivity analyses could help identify contributing factors. Despite the heterogeneity, the pooled effect sizes indicate a statistically significant improvement in DCR and ORR with Tislelizumab, with caution warranted when generalizing these findings. Group 1 significantly reduced all-cause mortality compared to Group 2 (RR = 0.89; 95% CI: 0.83–0.95; p = 0.0003), with no heterogeneity (I² = 0%). No significant differences were found in adverse events, except for ALT elevations. (RR = 1.36; 95% CI: 1.14–1.61; p = 0.0006, I² = 25%). Conclusions: Tislelizumab, with or without chemotherapy, demonstrates greater PFS and OS benefits compared to chemotherapy alone in patients with lung cancer. There was a significantly reduced all-cause mortality in the intervention group; however, the observed increase in the risk of ALT elevation underscores the need for vigilant liver function monitoring. When combined with chemotherapy, Tislelizumab presents a promising treatment option for lung cancer.

e16076 Background: Gastric cancer is the fourth leading cause of global cancer deaths. Despite declining incidence and mortality, it remains a significant contributor to the global disease burden. This study analyzes regional gastric cancer DALYs and mortality trends from 1990-2021 using the GBD database. Methods: The regional DALYs and mortality rates per 100,000 individuals aged 70+ from GBD 2021 were analyzed, with trends from 1990 to 2021 evaluated using AAPC, and statistical significance assessed by p-values. Results: In 2021, the greatest Age-standardized DALYs rates were recorded in Andean Latin America, with 3068.04 per 100,000; the lowest was found in High-income North America with 386.08 per 100,000. The most significant increase of DALYs rate from 1990 to 2021 was in Southern Sub-Saharan Africa, (AAPC = -0.3068%; 95% CI: -0.3852 to -0.2234; p < 0.000001), while in Western Europe, the largest decline was noted (AAPC = -2.9999%; 95% CI: -3.0164 to -2.9841; p < 0.000001). Andean Latin America was the region with the highest Age-standardized mortality rates (ASMRs) in 2021, at 207.58 per 100,000 while High-income North America had the lowest at 27.18 per 100,000. In Western Sub-Saharan Africa, the ASMRs were rising with an AAPC of -0.2601% (95% CI: -0.2872 to -0.2368; p < 0.000001), while Western Europe had the highest decline with an AAPC of -2.7658% (95% CI: -2.7895 to -2.7471; p < 0.000001). Conclusions: The global burden of diseases from 1990 to 2021 is regional in nature. In 2021, DALYs and mortality were predominantly high in Andean Latin America and East Asia and notably low in High-income North America. DALYs have risen across Southern Sub-Saharan Africa over three decades, and mortality increased over Western Sub-Saharan Africa, while both declined sharply in Western Europe. These trends underscore the importance of regionalized health solutions. DALY per 100,000. Metric Region 1990 2021 AAPC (1990-2021) HIGHEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PER 100,000 Andean Latin America 4469.23 3068.04 -1.14 East Asia 5507.72 2958.98 -1.99 High Income Asia Pacific 4849.23 2130.43 -2.71 LOWEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PER 100,000 High Income North America 758.59 386.09 -2.22 Australasia 1116.91 567.32 -2.16 South Asia 794.81 680.50 -0.46 HIGHEST MORTALITY RATE PER 100,000 Andean Latin America 293.65 207.58 -1.04 East Asia 324.60 188.92 -1.72 High Income Asia Pacific 316.44 161.94 -2.22 LOWEST MORTALITY RATE PER 100,000 High Income North America 51.24 27.19 -2.02 Australasia 74.36 41.81 -1.85 South Asia 47.50 41.95 -0.39

e16074 Background: Gastric cancer is a malignant disease characterized by the uncontrolled growth of cells in the stomach lining. It is a global health concern with regional variation in incidence and prevalence. This study examines the national mortality trends in adults aged 70 years and older from 1990 to 2021. Methods: GBD data was analysed to assess the mortality rates of Gastric cancer in individuals aged ≥ 70 years. The Estimated Annual Percentage Change (EAPC) was used to evaluate trends from 1990 to 2021, with p-values determining statistical significance. Results: From 1990 to 2021, the global prevalence of Gastric cancer increased, peaking in 2021. Japan recorded the highest prevalence (621.7379, UI: 525.93, 675.74), followed by the Republic of Korea and China.In 2021, Bolivia (Plurinational State of) had the highest mortality rate (309.7, CI: 400.9, 240.6), slightly lower than its 1990 rate (445.35, CI: 539.58, 362.14), which was the highest that year. Mongolia (303.15, CI: 378.8, 226.2) and Cabo Verde (265.1, CI: 322.6, 206.8) followed. The lowest mortality rates were observed in Morocco (20.9, CI: 25.9, 15.0), Namibia (20.93, CI: 25.93, 16.4), and Nigeria (23.27, CI: 32.3, 19.2).Countries with the largest EAPC increases included Egypt (0.98, CI: 1.84, -0.22), Honduras (0.31, CI: 0.7, -0.01), and Lesotho (0.16, CI: 0.597, -0.16). The greatest declines were seen in Austria (-0.72, CI: -0.68, -0.74), Czechia (-0.69, CI: -0.64, -0.74), and Hungary (-0.67, CI: -0.607, -0.72). Conclusions: Mortality rates associated with Gastric Cancer among individuals aged 70 and older increased globally from 1990 to 2021, notably in Egypt, Honduras and Lesotho, emphasizing the need for improved prevention, management, and research on underlying disparities. Mortality percent changes. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) HIGHEST MORTALITY PERCENT CHANGE Egypt 30.43 60.44 0.98 (1.84, -0.22) Honduras 140.76 184.48 0.31 (0.7, -0.01) Lesotho 77.18 90.26 0.16 (0.59, -0.16) LOWEST MORTALITY PERCENT CHANGE Austria 177.25 49.48 -0.72 (-0.68, -0.74) Czechia 168.73 51.51 -0.69 (-0.64, -0.74) Hungary 184.88 60.55 -0.67 (0.607, -0.72)

e16456 Background: Gastric cancer is one of the significant contributors of mortality and morbidity, especially in older patients. Analyzing national trends in the Disability adjust life years (DALY) helps identify the evolving burden of this disease among patients older than 70 years and highlights the regions requiring particular interventions. Methods: Using Global burden of disease data from 2021, national DALY rates per 100,000 people aged 70 and over with gastric cancer were assessed. The Estimated Annual Percentage Change (EAPCs) with p value taken as a statistical measure of significance, was used to evaluate trends from 1990 to 2021. Results: The analysis displays considerable contrasts in the trends of gastric cancer burden across nations. From 1990 to 2021, a rising trend in DALY EAPC was seen in Egypt (1.01883; 95% CI: -0.1931- 1.958) followed by Honduras (0.3262; 95% CI: 0.0177- 0.7456) and Lesotho (0.2253; 95% CI:-0.1326- 0.6995). Conversely, Austria (-0.7368; 95% CI: -0.7646 to -0.7087), Republic of Korea (-0.7095; 95% CI: -0.7620 to -0.6442) and Singapore (-0.6923; 95% CI: -0.7286 to -0.6553) reported a prominent decline in DALY EAPCs, reflecting significant progress in reducing burden. The DALY rates in 2021 also varied dramatically among nations. Highest DALY rate was observed in Bolivia (4882.7; 95% CI:3782.9- 6349.7) underscoring highest impact on healthcare system. Conversely, Morocco (329.69; 95% CI: 234.64- 410.12) recorded lowest DALY rate indicating comparatively better disease control or lower incidence. Conclusions: While some nations demonstrate remarkable progress in mitigating the burden of gastric cancer, others still face significant challenges. Highest increase in EAPC in Egypt, Honduras and Lesotho whereas significant decline in Austria, Korea, and Singapore indicates areas of target public health efforts. Future research should focus on understanding the causes of these disparities and evaluating the impact of interventions across it. DALY and EPAC. Country 2021 DALY rate EAPC(1990-2021) EAPC, 95% CI Egypt 1272.146 1.018834(highest) -0.193 to 1.959 Honduras 2880.563 0.32617 0.018 to 0.746 Lesotho 1555.79 0.225384 -0.133 to 0.699 Singapore 806.6098 -0.692396 -0.729 to -0.655 Republic of Korea 1961.151 -0.709502 -0.762 to -0.644 Austria 662.5105 -0.736826(lowest) -0.765 to -0.709 Morocco 410.1227(lowest) -0.17817 -0.387 to 0.097 Bolivia 4882.718(highest) -0.32185 -0.473 to -0.103

e16423 Background: Pancreatic cancer (PC) is one of the most aggressive malignancies, disproportionately affecting older adults. Leveraging data from the Global Burden of Disease (GBD), this study investigates gender-specific trends in disability-adjusted life years (DALYs) and mortality rates for PC among adults aged 70 and older from 1990 to 2021. Methods: DALYs and mortality rates associated with PC were extracted for both genders from the GBD-2021 study from 1990 to 2021. The Annual Percentage Change (APC) and the Average Annual Percentage Change (AAPC) were calculated, along with 95% confidence intervals (CI), to assess the statistical significance of the trends using the p-value. Results: In 1990, DALY rates were 837.25 for men and 711.95 for women, increasing to 950.68 and 768.31, respectively, by 2021. Mortality rates followed a similar pattern: men’s rates rose from 52.05 in 1990 to 61.37 in 2021, while women’s increased from 47.31 to 53.40. Men consistently experienced higher burdens than women. The AAPC analysis revealed that men exhibited a steeper rise in both DALYs and mortality rates associated with PC compared to women over the past three decades. Notably, the gender disparity was more evident in DALYs (+0.1929%) than in mortality rates (+0.1358%), with all AAPC values demonstrating statistical significance (p < 0.000001). Following the APC analysis, additional significant trends were identified. Among males, DALY rates demonstrated the most pronounced increase between 1997 and 2021 (APC: 0.5397, 95% CI: 0.5118, 0.5645), whereas in females, the most significant rise occurred from 1990 to 1993 (APC: 0.6593, 95% CI: 0.3608, 1.1016). Conversely, the slowest increase in DALY rates among females was observed between 1993 and 2003 (APC: 0.0925, 95% CI: -0.2053, 0.1641). For mortality rates, the most notable rise in males was observed between 2007 and 2010 (APC: 1.2314, 95% CI: 1.0292, 1.3195), while females experienced their sharpest escalation from 1990 to 1994 (APC: 0.6891, 95% CI: 0.4322, 1.0720). In contrast, the slowest rate of progression in mortality among females occurred between 1993 and 2002 (APC: 0.1736, 95% CI: 0.0180, 0.2368). Conclusions: Over the past three decades, men have experienced a significantly more pronounced rise in DALYs and mortality rates related to PC compared to women.These findings highlight the urgent need for gender-specific interventions to address the growing burden of PC in aging populations. Trends in DALY and mortality rates per 100,000 by gender (1990-2021). Metrics Gender 1990 2021 APC (1990-2021) Daly Rates per 100,000 Male 837.25 950.68 0.4422 Female 711.9 768.31 0.2493 Mortality Rates per 100,000 Male 52.05 61.37 0.5366 Female 47.31 53.40 0.4008

e16420 Background: Pancreatic cancer (PC) typically follows an indolent course and is often diagnosed at an advanced stage, contributing to its high mortality rate, particularly among older adults. Its aggressive nature makes it a significant global health burden, causing substantial mortality across nations. This analysis investigates national mortality trends in adults aged 70 years and older from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) Study. Methods: We utilized data from the GBD-Study 2021 to report the number of cases and age-standardized rates (per 100,000 population) of PC. To assess mortality trends from 1990 to 2021, we calculated the estimated annual percentage change (EAPC) along with corresponding 95%confidence intervals (CI), providing a robust evaluation of temporal patterns. Results: Over the past three decades, deaths attributable to PC have shown a significant increase globally. In 1990, the United States of America (USA) reported the highest number of PC-related deaths, followed by China and Japan. By 2021, however, China surpassed the USA, becoming the leading contributor to PC mortality, with Japan maintaining its position as the third highest.In 2021, the United Arab Emirates reported the highest mortality rate (148.15), which was more than double its 1990 rate (70.71). The Principality of Monaco (140.87) and Uruguay (129.39) held the second and third highest mortality rates, respectively. The lowest mortality rates were recorded in Mozambique (8.18), Malawi (8.98), and Sao Tome and Principe (9.01).Countries with the largest increases in the EAPC included Turkmenistan (EAPC: 15.16, 95% CI: 10.92, 21.02), Republic of Cabo Verde (EAPC: 13.60, 95% CI: 8.56, 19.48), and Mongolia (EAPC: 4.80, 95% CI: 3.11, 7.26). In contrast, the greatest declines were observed in the Republic of San Marino (EAPC: -0.32, 95% CI: -0.52, -0.07), Guam (EAPC: -0.27, 95% CI: -0.41, -0.13), and Greenland (EAPC: -0.24, 95% CI: -0.44, 0.007). Conclusions: Globally, mortality rates associated with PC among individuals aged 70 and older increased from 1990 to 2021, with particularly notable rises in Turkmenistan, Republic of Cabo Verde, and Mongolia. These findings underscore the critical need for enhanced prevention strategies, improved management, and research to address underlying disparities. Mortality percent change. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) Highest mortality percent change Turkmenistan 1.19 19.34 15.16 (10.92, 21.02) Republic of Cabo Verde 6.47 94.55 13.60 (8.56, 19.48) Mongolia 10.21 59.24 4.80 (3.11, 7.26) Lowest mortality percent change Republic of San Marino 89.48 60.47 -0.32 (-0.52, -0.07) Guam 32.46 23.51 -0.27 (-0.41, -0.13) Greenland 169.52 127.96 -0.24 (-0.44, 0.007)