Citations

e16419 Background: Pancreatic cancer remains one of the most lethal malignancies worldwide. While high-income regions have long faced higher rates, recent trends show that lower-income regions are also beginning to see an increase. This study explores how pancreatic cancer incidence and prevalence have changed over the past 30 years among adults aged 70 and older assessing regional differences. Methods: We analyzed data from the Global Burden of Disease (GBD) spanning three decades (1990–2021) to assess pancreatic cancer incidence and prevalence rates among adults aged 70+. Data focused on different regions worldwide, grouping them by income levels using the Socio-demographic Index (SDI) and annual changes in incidence and prevalence rates were calculated. Results: In 2021, High-income Asia Pacific had the highest incidence rate at 119.52 per 100,000, whereas Low SDI regions had the lowest at 12.01 per 100,000. High-income regions accounted for the majority of cases, with over 140,000 reported, compared to fewer than 3,000 in the lowest-income areas. Andean Latin America experienced significant APC fluctuations, with a sharp rise from 2015 to 2019 followed by a decline, while High-income North America saw a recent decrease in incidence. Overall, most regions exhibit a steady increase in pancreatic cancer prevalence, with higher AAPCs in Sub-Saharan Africa, North Africa, and parts of Asia, while high-income regions show more moderate increases. Trend analysis reveals significant trends in pancreatic cancer incidence and prevalence among individuals aged 70+. Western Sub-Saharan Africa has the highest Average Annual Percent Change (AAPC) at 2.3248%, indicating the most substantial increase in prevalence from 1990 to 2021, followed by North Africa and the Middle East at 1.9906%. Low-middle SDI regions also show a steady rise with an AAPC of 1.718%, while high-income regions like High-income Asia Pacific report a notable AAPC of 1.595%. Conclusions: Our findings show a concerning rise in pancreatic cancer among older adults, with the most dramatic increases in regions like Western Sub-Saharan Africa and North Africa. To tackle this growing challenge, we need focused efforts on prevention, early detection, and accessible care, especially in lower-resource settings. Incidence percent changes. Metric Region 1990 2021 AAPC (1990-2021) Highest incidence percent change Western Sub-Saharan Africa 7.62 15.38 2.31 North Africa and Middle East 20.97 37.23 1.91 Lowest incidence percent change Caribbean 41.51 41.36 -0.016 Southern Latin America 74.05 73.89 0.006 Highest prevalence percent change Western Sub-Saharan Africa 4.54 9.21 2.32 North Africa and Middle East 12.49 22.77 1.99 Lowest prevalence rate percent change Caribbean 25.02 25.38 0.02 Southern Latin America 44.78 45.45 0.06

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.

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)

e22570 Background: Aging into the seventh decade of life marks a pivotal shift in cancer susceptibility, with pancreatic cancer (PC) emerging as one of the most relentless threats to global health. This study utilizes three decades of Global Burden of Disease (GBD) data to unravel unprecedented insights into the prevalence and incidence of PC among adults aged 70 and older. Methods: We analyzed data from the GBD study to assess the temporal trends in the incidence and prevalence of PC from 1990 to 2021. The Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC), along with 95% confidence intervals (CI), were utilized to assess the overall trends, with statistical significance evaluated using p-values. Results: Over the past three decades, the global burden of PC has surged significantly. In 1990, the global incidence of PC stood at 45.12 per 100,000, escalating to 54.47 per 100,000 by 2021. Likewise, global prevalence increased from 30.33 per 100,000 in 1990 to 40.60 per 100,000 in 2021, with incidence rates consistently exceeding prevalence, suggesting an accelerating number of new cases of PC worldwide. The AAPC analysis revealed a significant upward trajectory in both global incidence (AAPC: 0.6085, 95% CI: 0.5801, 0.6273 p < 0.000001) and prevalence (AAPC: 0.9467, 95% CI: 0.9188, 0.9659 p < 0.000001) of PC. Following the APC analysis, several notable trends emerged. The global incidence of PC experienced its most substantial increase between 2003 and 2010 (APC: 1.0806, 95% CI: 0.9817, 1.3206 p < 0.000001), while the slowest growth in incidence occurred from 1990 to 2003 (APC: 95% CI: 0.9817, 1.3206 p = 0.000400). Conversely, the global prevalence of pancreatic cancer saw its most pronounced rise between 1998 and 2001 (APC: 2.0389, 95% CI: 1.2005, 2.1962 p < 0.000001), with the slowest increase occurring from 1994 to 1998 (APC: 0.4632, 95% CI: 0.2544, 1.9767 p = 0.001200). Conclusions: The persistent rise in both incidence and prevalence of PC over the past three decades underscores a critical global health challenge, with a marked acceleration in recent years. These findings highlight the urgent need for targeted interventions and a deeper understanding of the factors driving this expanding burden, particularly as the incidence consistently outpaces prevalence. Metric Overall 1990 2021 AAPC with 95% CI (1990-2021) INCIDENCE RATES PER 100,000 Global Incidence 45.12 54.47 0.61 (0.58, 0.63) PREVALENCE RATES PER 100,000 Global Prevalence 30.33 40.60 0.95 (0.92, 0.97)

10544 Background: Incorporation of Polygenic Risk Scores (PRS) can refine traditional breast cancer risk assessment models to provide precise estimates of breast cancer risk. However, the impact of such an integrated model on clinical decision-making related to breast cancer surveillance and preventive strategies is not fully understood. Methods: The GENRE-2 is a prospective single-arm multisite clinical trial (NCT04474834) incorporating PRS into standard breast cancer risk assessment models to determine the impact of PRS on clinical decisions on breast cancer prevention and surveillance. Women at high risk of breast cancer due to NCI-BCRAT 5-year risk of ≥ 3%, or IBIS (Tyrer-Cuzik) 10-year breast cancer risk of ≥5%, biopsy-proven high-risk breast lesion, or a pathogenic variant (PV) in ATM , BRCA1, BRCA2, CHEK2 or PALB2 , were enrolled from five sites in the United States. All women were invited to complete surveys on their breast surveillance and cancer prevention decisions based on pre-PRS standard risk models and post-PRS risk estimation, and further annual surveys are planned for 10 years. Results: Among 902 women enrolled in the study, 605 (median age: 52 years) received PRS results and completed a survey to date. Of those who received PRS results,195 (32.2%) were PV carriers. Among non-carriers, the median 10-year and lifetime pre-PRS IBIS-based risk was 10.0% and 28.7%, respectively. Among PV carriers, the CanRisk-based 10-year and lifetime pre-PRS risk estimates were 6.3% and 25.2% for ATM , 22.3% and 77.6% for BRCA1 , 18.5% and 77.7% for BRCA2 , 7.1% and 25.7% for CHEK2 , and 16.8% and 38.0% for PALB2 PV carriers, respectively. After the incorporation of PRS, the lifetime risk of breast cancer increased by at least 10% in 31% of non-carriers and 7.7% of PV carriers and decreased by at least 10% in 10.7% of non-carriers and 7.7% of PV carriers. The proportion of non-carriers with lifetime risk < 20% or > 40% changed from 17.3% and 22.0%, respectively, in the pre-PRS evaluation to 24.4% and 32.9%, in the post-PRS evaluation. A higher lifetime post-PRS score was associated with intent to take preventive action (surgery or endocrine agents). In non-carriers, the proportion of women with a lifetime risk < 20% with intent to take preventive action was 11%, compared to 36.8% of those with a lifetime risk > 40% (p < 0.001). Similarly, in PV carriers, the proportion of women with lifetime risk < 20% with intent to take preventive action was 20.8% compared to 41.1% of those with lifetime risk > 40% (p = 0.015). Conclusions: The GENRE-2 trial demonstrates that the incorporation of PRS into breast cancer risk assessment models in high-risk women is feasible and leads to clinically meaningful changes in breast cancer risk estimates and decision-making regarding preventive strategies. Evaluation of the implementation of breast cancer risk management strategies in study participants is ongoing and will be reported. Clinical trial information: NCT04474834 .

e19022 Background: Chronic lymphocytic leukemia (CLL) is a common adult leukemia that originates by dysfunctional development of the lymphocytes. Acalabrutinib, a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, has demonstrated promising outcomes as a targeted therapy alternative to chemoimmunotherapy for treating CLL. The objective of this retrospective analysis was to compare the safety profiles of acalabrutinib and chemoimmunotherapy in patients with CLL and to evaluate the potential of acalabrutinib as an alternative therapeutic option. Methods: We conducted a retrospective cohort analysis using the TriNetX platform analyzing data of patients diagnosed with CLL from January, 2000 to January, 2025. Data was classified into cohorts on the basis of treatment with either acalabrutinib or chemoimmunotherapy. Propensity score matching analysis was carried out to balance their demographic and clinical characteristics. Demographic factors included age (≥18 years), sex, race, and ethnicity. Outcomes assessed included all cause death, atrial fibrillation, hypertension, acute heart failure, ventricular arrythmias, and bleeding. Kaplan-Meier survival analysis was employed. Results: A total of 4,006 patients were included in the analysis, 847 received acalabrutinib and 3,172 underwent chemoimmunotherapy, with a mean age of 70±11 and 69±14 years respectively. Participants were mostly male, with the majority of the patients being non-Hispanic Whites. Median period of follow up was 578 and 925 days respectively, incidence and risk of mortality and adverse events were assessed. A lower risk of mortality was noted with acalabrutinib (RR: 0.407; 95%CI: 0.32, 0.51; p<0.0001). Additionally, atrial fibrillation developed in fewer than 10 patients on use of acalabrutinib, thus carrying significantly lower odds (odds ratio (OR):0.3; 95%CI: 0.16, 0.58; p=0.001) than chemoimmunotherapy, which reported atrial fibrillation in 120 patients. Similarly, significantly lesser incidence of hypertension was noted on use of acalabrutinib, implying safer drug profile. Bleeding risk was also reduced in the acalabrutinib cohort and was statistically significant (OR:0.36, 95%CI: 0.24, 0.52; p<0.0001). The odds of acute heart failure (OR:1.25, 95%CI: 0.61, 2.57; p=0.54) and ventricular arrhythmia (OR:1.5, 95%CI: 0.72, 3.14; p=0.2) were statistically nonsignificant. Conclusions: The use of acalabrutinib in patients with CLL was associated with statistically significant better safety profile, with lesser risk of mortality, bleeding events and atrial fibrillation. Clinicians may consider using acalabrutinib as a superior treatment modality in the treatment of CLL. Further research maybe required to optimize treatment protocols in the best interest of patients.

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.

ABSTRACT The lower infrastructure requirements of portable ultra‐low field MRI (ULF‐MRI) systems have enabled their use in diverse settings such as intensive care units and remote medical facilities. The UNITY Project is an international neuroimaging network harnessing this technology, deploying portable ULF‐MRI systems globally to expand access to MRI for studies into brain development. Given the wide range of environments where ULF‐MRI systems may operate, there are external factors that might influence image quality. This work aims to introduce the quality control (QC) framework used by the UNITY Project to investigate how robust the systems are and how QC metrics compare between sites and over time. We present a QC framework using a commercially available phantom, scanned with 64 mT portable MRI systems at 17 sites across 12 countries on four continents. Using automated, open‐source analysis tools, we quantify signal‐to‐noise, image contrast, and geometric distortions. Our results demonstrated that the image quality is robust to the varying operational environment, for example, electromagnetic noise interference and temperature. The Larmor frequency was significantly correlated to room temperature, as was image noise and contrast. Image distortions were less than 2.5 mm, with high robustness over time. Similar to studies at higher field, we found that changes in pulse sequence parameters from software updates had an impact on QC metrics. This study demonstrates that portable ULF‐MRI systems can be deployed in a variety of environments for multi‐center neuroimaging studies and produce robust results.

Abstract INTRODUCTION Clinicians’ views on the clinical readiness of Alzheimer's disease (AD) blood biomarkers (BBMs) are not well understood. METHODS The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment Biofluid‐Based Biomarkers Professional Interest Area conducted a survey to elicit clinician opinions on AD BBM implementation, including contexts of use, assay selection, reporting, and result interpretation. RESULTS Clinician respondents ( n = 212) practiced in Europe (56%), North America (24%), the Caribbean and Central/South America (11%), and other continents (9%). Most respondents were medical doctors (80%) practicing in secondary or tertiary care (88%). For 56%, cerebrospinal fluid AD biomarkers or amyloid positron emission tomography were accessible, but 48% agreed and 52% disagreed with the implementation of AD BBMs in any clinical context. Respondents emphasized the need for data from diverse populations and educational resources to support test interpretation. DISCUSSION Surveyed clinicians generally agreed with published appropriate use recommendations but were divided on AD BBM readiness for clinical use. Highlights A survey of clinicians was conducted regarding clinical readiness of Alzheimer's disease (AD) blood biomarkers (BBMs). Views were split on AD BBM clinical readiness: 48% agreed, 52% disagreed. Most responders supported AD BBM use for treatment decisions. Most responders opposed AD BBM testing in asymptomatic individuals. Test performance data and educational materials to aid interpretation were of high importance.