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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)

e16072 Background: Gastric cancer is a leading cause of mortality worldwide, with pronounced variations in outcomes across populations. This study investigates U.S. trends in age-adjusted mortality rates (AAMRs) for gastric cancer from 1999 to 2023, examining differences by gender, race, region, and urbanization to uncover critical patterns and inequities. Methods: Data were extracted from the CDC WONDER database using ICD-10 code C16 to identify gastric cancer-related deaths in adults aged 25 and older. AAMRs per 1,000,000 population were calculated and stratified by year, gender, race/ethnicity, geographic region, and urban-rural classification. Trends were analyzed using Joinpoint regression to determine annual percentage changes (APC) and 95% confidence intervals (CI). Statistical significance was set at p < 0.05. Results: From 1999 to 2023, there were 312,300 gastric cancer deaths (185,391 men, 126,909 women). Overall, AAMRs declined consistently, with APCs of -3.4 for the period 1999 to 2007, -2.2 for 2007 to 2018, and -1.2 for 2018 to 2023. Men showed a more pronounced decline, with APCs of -3.6 for 1999 to 2009 and -2.2 for 2009 to 2023, compared to women, who had APCs of -3.1 for 1999 to 2008, -1.9 for 2008 to 2018, and -0.8 for 2018 to 2023. Non-Hispanic Black populations experienced a decline in AAMR with an APC of -3.3 for 1999 to 2020, while Hispanic/Latino and Asian/Pacific Islander populations showed declines with APCs of -2.8 for 1999 to 2011 and -3.8 for 1999 to 2020, respectively. Metropolitan areas saw AAMR reductions with APCs of -3.3 for 1999 to 2008 and -2.2 for 2008 to 2020, while non-metropolitan areas had larger initial declines with an APC of -3.6 for 1999 to 2006 but slower decreases with an APC of -2.0 for 2006 to 2020. Geographically, the Northeast had the highest AAMR (62.9), followed by the West (61.7), South (57.4), and Midwest (50.9). Hawaii recorded the highest state-level AAMR (96.5), while Wyoming had the lowest (36.6). States in the top 90th percentile included Alaska, California, and New York, whereas Utah, Idaho, and Iowa were among the lowest. Conclusions: Gastric cancer mortality in the U.S. has declined over the past two decades, but the pace of reduction has slowed in recent years. Significant disparities persist across gender, racial, and geographic groups, underscoring the need for targeted interventions to address these inequities and improve outcomes in vulnerable populations.

e13808 Background: Cancer is a leading cause of death for Latinos. They experience higher rates than their white peers of preventable, infectious-agent-causing-cancers, such as stomach & liver cancer. Latina women have experienced a 1% rise in cancer cases since 2011 & Latino children & adolescents experience higher rates of leukemia than any other racial/ethnic group. Latinos face disparities in access to healthcare, cancer screening & treatment, medical representation & experience lower rates of survival due to late-stage cancer diagnosis. Methods: To combat these inequities & identify equitable interventions for Latino health, the Institute of Health Promotion Research & the Mays Cancer Center established the Advancing the Science of Cancer in Latinos (ASCL) Conference. The fourth ASCL Conference convened in San Antonio, TX from February 21-23, 2024. The conference objectives were 1) Examine the intersection of health equity & biological underpinnings in cancer control, prevention, and treatment 2) Foster collaborative initiatives among attendees aimed at addressing cancer-related health disparities within the Latino community. The conference hosted 286 participants (speakers, researchers, physicians, healthcare professionals, patient advocates & students). It comprised of 23 sessions (3 keynotes, 6 plenaries, 6 breakouts, 3 general sessions, 1 special session, 1 lunch panel session) featuring insights from 51 speakers, a poster session highlighting 80 research abstracts & a rapid-fire session tailored for early-career investigators. Sessions focused on multiple topics relevant to Latino cancer research, clinical trials, survivorship, patient advocacy, climate change impacts on cancer, precision medicine, health policy & social determinants of health. Results: A post-conference survey from a cohort of 48 respondents underscored high levels of satisfaction, with 90% expressing contentment regarding the conference experience. Nearly all respondents (98%) rated the relevance of conference content to Latino cancer science as excellent, with 93% regarding the conference as an exceptional platform for information exchange. Impressions regarding session quality were positive, with 90% of respondents indicating a high level of satisfaction, & all survey respondents acknowledging the objectivity, balance & absence of commercial bias in the session content. Conclusions: Results showed that the resounding positivity in attendee feedback reflects the conference's success in fostering meaningful engagement among attendees. The ASCL conference facilitated an understanding of cultural nuances and barriers specific to the Latino community, stimulating collaborative efforts aimed at enhancing Latino health outcomes. Overall, this analysis affirms the conference's success in achieving its stipulated objectives and underscores the need of having consistently coordinated research endeavors to reduce Latino health disparities.

e16001 Background: Esophageal carcinoma ranks among the top 10 malignancies in the world, contributing to high morbidity and mortality. With radiotherapy being one of the most administered treatment options, different variations of administration have evolved. Two such variations include intensity-modulated radiotherapy and 3D conformational radiotherapy. These modalities have been investigated for their efficacy and rate of adverse events. However, conclusions from the trials conducted have been variable. In this systematic review and meta-analysis, we aim to collate these findings to assess the exposure of cancerous cells and rates of adverse events following IMRT or 3D-CRT. Methods: A comprehensive literature search was conducted across three databases for all articles published from inception till September 2024. All primary studies evaluating the comparative efficacy of IMRT vs 3D-CRT were included. Outcomes assessed include dose volume histograms (DVHs) at heart and lung, Dmax at the spinal cord, and irradiation toxicity. Data analysis was conducted in RevMan 5.4 using a random-effects model. Results: A total of twenty records were included in the study, with a sample size of 3090 patients. Radiation dosage, estimated as DVHs, was equal across both regimens at heart (MD: 2.67; 95%CI: –0.15 to 5.48; P = 0.06), except at 40 Gy of radiation, where a lower DVH was noted among patients being administered IMRT (MD: 6.64; 95%CI: 0.25 to 13.03; P = 0.04). At the lung, a higher DVH was noted, especially for doses of 20 Gy or above, on using IMRT. Similarly, a lower dosage in the spinal cord was noted in the IMRT group (MD: 2.87; 95%CI: 1.04 to 4.70; P = .002). Consequently, a lower risk of esophagitis was noted among the IMRT group (OR: 1.54; 95%CI: 1.14 to 2.07; p = 0.009]). While considering patient outcomes, the odds of survival were higher in the IMRT group at 3 years post-treatment (OR: 0.53; 95%CI: 0.31 to 0.92; P = 0.02). Conclusions: IMRT was superior to 3D-CRT in terms of volume of tissue irradiated and lower spinal toxicity. A higher chance of survival was noted in the IMRT group. Further trials are needed to strengthen these findings. Outcome Mean Difference (MD) 95% confidence interval (CI) P value Mean dosage at lung 1.14 0.6, 1.68 <0.0001 Mean dosage at heart 2.67 -0.15, 5.48 0.06 Radiation esophagitis Odds ratio, OR: 1.38 1.09, 1.76 0.009 Radiation pneumonitis OR:1.37 0.62, 3.01 0.43 3-year OS OR: 0.69 0.56, 0.84 0.0003 5-year OS OR: 0.53 0.31, 0.92 0.02 Maximum dosage at spinal cord 2.87 1.04, 4.7 0.0002

4020 Background: In previously treated patients (pts) with advanced extra-pancreatic NET (epNET) or pancreatic NET (pNET), cabozantinib (cabo) demonstrated improved progression-free survival compared to placebo (pbo) in the CABINET trial (NCT03375320). Here we present HRQOL data from CABINET. Methods: Pts with previously treated unresectable, locally advanced or metastatic epNET or pNET were randomized (2:1) in separate cohorts to receive cabo 60 mg daily vs pbo. HRQOL was an exploratory endpoint measured using the EORTC QLQ-C30, QLQ-GI.NET21, Patient Global Impression of Change (PGIC), and PRO-CTCAE questionnaires. Optional participation was by paper surveys at baseline and every 12 weeks (wks) until disease progression or new anticancer therapy. Mean changes from baseline were compared between treatment arms at wk12 using general linear mixed models. Minimally important within-arm improvements and between-arm differences were defined as 8 points on the C30 Global Health Status (GHS)/QOL Scale. PGIC was dichotomized as improved vs unchanged/worsened and compared using Chi-squared tests. Rates of pt-reported adverse events (AEs) by PRO-CTCAE were baseline-adjusted and compared using Fisher’s exact tests. Results: 172 pts (113 cabo, 59 pbo) with epNET and 81 pts (53 cabo, 28 pbo) with pNET consented for survey participation. Pts completed 524 (82%) of 640 expected surveys across baseline, wk12, and wk24. For epNET, C30 GHS/QOL was significantly improved at wk12 in pts receiving cabo (mean change 9.5, standard error (SE) 2.2, p < 0.001) but not pbo (mean change 0.2, SE 3.1, p = 0.95) resulting in significantly different mean changes from baseline between arms (p = 0.02). For pNET, C30 QHS/QOL was significantly improved at wk12 in pts receiving cabo (mean change 8.0, SE 3.0, p = 0.008) but not pbo (mean change 6.8, SE 4.4, p = 0.12); mean changes from baseline did not statistically differ between arms (p = 0.82). No significant differences in mean changes from baseline at wk12 in C30 Physical, Role, Emotional, Cognitive and Social Function were observed between arms in the epNET or pNET cohorts. In both cohorts at wk12, pts on cabo reported improved overall status as measured by PGIC more often than those on pbo (epNET: 38% vs 19%, p = 0.04; pNET: 57% vs 18%, p = 0.006). Rates of pt-reported AEs were statistically significantly higher in cabo for diarrhea (68% vs 53%), hand-foot syndrome (57% vs 26%), mouth or throat sores (47% vs 27%), and dysgeusia (67% vs 37%) [all p < 0.05]. GI.NET21 data will be presented. Conclusions: Although cabo is associated with pt-reported AEs consistent with its known safety profile, global HRQOL was maintained. A higher proportion of patients receiving cabo reported improved overall status. Results support cabo as a treatment option for pts with previously treated advanced NET that preserves patient HRQOL. Clinical trial information: NCT03375320 .

e16481 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 investigates the regional incidence and prevalence of gastric cancer among adults aged 70 and older from 1990 to 2021, utilizing data from 26 global regions. Methods: Global Burden of Disease (GBD) data for 2021 were analyzed to assess regional incidence and prevalence of gastric cancer among adults aged ≥ 70. The Annual Average Percentage Change (AAPC) was calculated to evaluate trends from 1990 to 2021, with statistical significance determined using p-values. Results: In 2021, East Asia has the highest incidence (273403) followed by Middle SDI (189383) and High-middle SDI (176691). Highest Prevalence numbers were recorded for East Asia (398,000) followed by High SDI (337,000) and High-middle SDI (250,000). With regards to rates per 100,000, Oceania has the lowest incidence (257) as well as prevalence (252) followed by Central Sub-Saharan Africa (I:1142 , P: 1081) and Southern Sub-Saharan Africa (I:1295, P: 1227). The largest increase in AAPC of incidence was exhibited by Western Sub Saharan Africa (-0.24, CI: -0.27 to -0.23), Southern Sub Saharan Africa (-0.29, CI: 0.37 to -0.22), and South Asia (-0.306, CI: -0.422 to -0.158) regions, while South Asia (-0.087, CI: -0.1748 to 0.0308), East Asia (-0.0952, CI: 0.0284 to 0.1606), and Andean Latin America (-0.1696, CI: -0.3498 to -0.0381) showed largest increase in AAPC of prevalence. Western Europe region had the greatest decline in AAPC of incidence (-2.3995, CI: -2.4374 to -2.3691) followed by Central Europe (-2.2010, CI: -2.3007 to -2.1445) and Eastern Europe (-2.1554, CI: -2.212 to -2.0925 ) regions while Central Asia had the greatest decline in AAPC of prevalence (-1.9281, CI: -2.0109 to -1.8522) followed by High Income Asia Pacific (-1.8268, CI: -1.8926 to -1.7913) and Eastern Europe (-1.8103, CI: -1.8631 to -1.7623). All AAPC values were statistically significant (p < 0.000001). Conclusions: The East Asia region exhibited the highest incidence and prevalence, highlighting the vulnerability of these populations, while Central Sub-Saharan Africa bore the least burden. Notably, several regions, particularly in Asia, experienced substantial increases in both incidence and prevalence, emphasizing the need for targeted interventions. Conversely, some regions, such as Europe, showed encouraging declines in prevalence, suggesting that effective prevention and control strategies can be implemented. These findings underscore the importance of tailored approaches to address the evolving burden of Gastric Cancer.

AbstractINTRODUCTIONThis study investigated the role of the ubiquitin–proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining cerebrospinal fluid (CSF) levels of UPS proteins.METHODThe SOMAscan assay was used to detect changes in UPS proteins in mutation carriers (MCs) relative to disease progression; imaging and CSF biomarkers of amyloid, tau, and neurodegeneration measures; and Clinical Dementia Rating scale.RESULTSSubtle increases in specific ubiquitin enzymes were detected in MCs up to two decades before symptom onset, with more pronounced elevations in UPS‐activating enzymes near symptom onset. Significant correlations were found between UPS proteins and Alzheimer's disease (AD) biomarkers, especially between autophagy markers and late‐stage tau biomarkers, microglia, and axonal degeneration.DISCUSSIONThe rise in UPS proteins alongside tau‐related markers suggests UPS involvement in tau neurofibrillary tangles. Elevated CSF UPS proteins in DIAD MCs may serve as indicators of disease progression, and may support the UPS as a therapeutic target in AD.Highlights This study investigates the ubiquitin‐proteasome system (UPS) in Dominantly Inherited Alzheimer's Disease (DIAD), highlighting early molecular changes linked to disease progression. Using SOMAscan proteomics, we identified significant UPS protein alterations in cerebrospinal fluid of mutation carriers, notably up to 20 years before clinical symptom onset. Correlations between UPS protein levels and Alzheimer's biomarkers, particularly tau and neurodegeneration markers, suggest a strong association between UPS dysregulation and tau pathology in DIAD. Dynamic UPS changes align with A/T biological staging: UPS proteins were shown to increase across Aβ/tau (A/T) groups, with largest increases in the A+/T+ group, reinforcing their role in late‐stage tau pathology and disease progression. These findings underscore the potential of UPS proteins as early biomarkers for Alzheimer's disease progression and as novel therapeutic targets, especially in tau‐pathology‐driven neurodegeneration. This work contributes to understanding AD pathogenesis, by emphasizing the importance of protein quality control systems and by offering avenues for future biomarker discovery and therapeutic development in Alzheimer's disease.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Background Mechanical thrombectomy for ischemic stroke has traditionally been performed via transfemoral access (TFA). However, newer literature on the subject suggests that transradial access (TRA) may be equally efficacious. Methods Online databases (including PubMed, Google Scholar, Embase, and Cochrane) were queried from inception until May 2024. Abstracts and full texts were screened according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Risk of bias assessment was performed using standardized screening tools. All dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). RevMan was used to perform the statistical analysis. Results Thirteen observational studies and one randomized clinical trial (RCT) were included in this meta-analysis. The total sample size was 4973, 4074 patients (81.2%) were in the TFA group, and 899 (18.8%) were in the TRA group. No significant differences were observed between the two groups in terms of successful recanalization (OR = 0.92; 95% CI 0.66–1.27; p = 0.60), first-pass recanalization (OR = 0.84; 95% CI 0.69–1.01, p = 0.06), access to reperfusion time (mean difference −2.99 min; 95% CI −8.33 to 2.44, p = 0.27), and favorable functional outcome. Mortality and rates of intracranial hemorrhage were comparable between the two groups, but access site complications were significantly lower in the TRA group (OR = 0.57; 95% CI 0.37–0.88; p = 0.01). Conclusion TRA for thrombectomy in large vessel ischemic strokes is comparable to TFA in terms of efficacy and has a lower incidence of access site complications. RCT data comparison of the two techniques is limited, underscoring the importance of conducting trials.