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Importance Primary brain and central nervous system cancer (collectively referred to as CNS cancer) comprises 2% of all human cancers and poses significant health and economic challenges in the United States. Objective To analyze CNS cancer burden in the US, stratified by time, location (state and division), sex, age group, and Sociodemographic Index (SDI). Design, Setting, and Participants This cross-sectional study involved a repeated analysis of Global Burden of Disease Study (GBD) 2021 data in 2024. Using data from 183 sources, CNS cancer metrics in the US were estimated across states and years. US CNS cancer metrics across all sexes and age groups were included in the GBD. Exposure CNS cancer diagnosis. Main Outcomes and Measures Overall and age-standardized estimates of the incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability per 100 000 population, including 95% uncertainty intervals (UIs), and time trends. Results In 2021, for all age groups and sexes across the US, there were 31 780 incident cases (95% UI, 29971.1 to 32843.9). Age-standardized incidence, DALYs, and mortality rates per 100 000 population were 6.91 (95% UI, 6.58 to 7.12), 134.38 (95% UI, 129.83 to 137.95), and 4.1 (95% UI, 3.87 to 4.22), respectively. Despite no significant change observed in the overall incidence between 1990 and 2021, DALY and mortality rates decreased by 15.77% (95% UI, −17.75% to −13.68%) and 8.41% (95% UI, −11.09% to −6.22%), respectively. Substantial geographic variability was noted. Mississippi, Alabama, Kentucky, and Kansas (West North Central and East South Central divisions) and West Virginia faced persistently high burdens over the past 30 years. Sex differences were evident; disease burden was consistently higher in males compared with females. Age-specific estimates showed a bimodal distribution: the youngest group (<5 years) showed a significant decrease in incidence rate (−34.42% to −11.56%), whereas older age groups (>70 years) experienced increasing trends. DALYs and mortality rates were negatively correlated with SDI (ρ = −0.6860 and ρ = −0.6391; P < .001). Conclusions and Relevance These findings provide valuable insights into the CNS cancer burden across the US by age, sex, location, and SDI, enabling better public health status assessments, health care policy restructuring, and resource redistribution for improved care.

Background: Sudden cardiac death (SCD) is a leading cause of mortality in the U.S., with emerging evidence pointing to racial disparities and the impact of social vulnerability. Yet, geographic patterns integrating race and county-level vulnerability remain underexplored. Objective: To identify U.S. counties where socially vulnerable communities, stratified by race/ethnicity, experience disproportionate burdens of SCD-related mortality. Methods: We analyzed county-level data (1999-2020), integrating age-adjusted mortality rates (AAMR) for SCD with the 2020 CDC Social Vulnerability Index (SVI). Counties were categorized into SVI quartiles (Q1: Low to Q4: High Social Vulnerability). Analyses were stratified by race/ethnicity: Black or African American, Hispanic/Latino, White, American Indian/Alaska Native (AI/AN), and Asian/Pacific Islander (API). We used RStudio (v2023.06.1) for data cleaning, ANOVA testing, and descriptive analysis. “Unreliable” mortality values were handled as missing or set to zero, with only valid AAMR > 0 included. Hotspot counties were identified by selecting the top decile of AAMR SCD within Q4 SVI counties. Results: Significant disparities emerged across SVI quartiles for Black (p = 0.0003), Hispanic (p < 0.0001), and White (p < 0.0001) groups. Mean AAMR more than doubled from low to high SVI counties in Black communities (17.0 to 39.4 per 100,000). White and Hispanic groups showed smaller but consistent increases. API (p = 0.60) or AI/AN (p = 0.63) groups showed no significant trends. Madison Parish, LA appeared in the top-10 highest-burden counties across all groups. Black populations faced extreme rates in some SVI counties (e.g., Madison Parish, LA: 351.4 per 100,000), while API groups had low AAMR even in vulnerable areas. Data misclassification limited interpretation in the Hispanic group. Conclusions: Black, Hispanic, and White populations showed significant differences in SCD mortality tied to social vulnerability. Black populations in the most vulnerable areas experienced more than twice the rate of mortality compared to those in less vulnerable areas, suggesting a strong correlation between social vulnerability and SCD mortality in Black communities. API and AI/AN groups showed no significant associations, likely due to small sample sizes. Madison Parish, LA reflects the compounded impact of structural disadvantage. Findings support targeted interventions in socially and racially vulnerable counties to reduce preventable cardiac deaths.

Abstract Disclosure: M. Kakakhel: None. S. Fatima: None. H. Ahmad: None. A. Ibrahim: None. W. Rahman: None. R. Haider: None. H. Jawad: None. A. Qadeer: None. M. Khawar: None. F. Ahmed: None. J. Ikram: None. R. Kirchoff: None. Background: Across the world, type 1 diabetes mellitus (T1DM) is a major health problem for teenagers and young people. This study aims to examine the incidence and prevalence of T1DM by gender in the 15-39 age range between 1990 and 2021. Methods: We analyzed data from the Global Burden of Disease (GBD) to evaluate incidence and prevalence rates of T1DM in each gender from 1990 to 2021. The Annual Percentage Change (APC) and The Annual Average Percentage Change (AAPC) was used to assess trends, with p-values determining the statistical significance. Results: From 1990 to 2021, the global prevalence of T1DM was found to be increased steadily for both genders, with the highest rates recorded in 2021: 247.32 per 100,000 for females and 246.47 per 100,000 for males. Incidence rates in 2021 showed a contrasting pattern, with males exhibiting higher rates (7.18 per 100,000) compared to females (5.98 per 100,000). AAPC analysis showed that males exhibit a faster rise in both prevalence and incidence compared to females over the study period. The difference in AAPC between males and females is more pronounced for prevalence (+0.3748%) compared to incidence (+0.1956%), with all AAPC values being statistically significant (p &lt; 0.000001). Following the APC analysis, other significant trends were revealed. Male incidence experienced the greatest increase during 2015-2021, with an APC of +1.9033% (p &lt; 0.000001), whereas female incidence increased most between 2011 and 2014 (APC = +1.3050%; p &lt; 0.000001). In contrast, the most significant decline in incidence was observed in females during 1990-1992, with an APC of +0.1665% (p = 0.006799), which was the lowest increase in the dataset. For prevalence, males exhibited the highest increase during 2015-2021, with an APC of +1.3938% (p &lt; 0.000001), whereas females had their peak increase during 2006-2009, with an APC of +0.8957% (p &lt; 0.000001). The slowest increase in prevalence for females occurred during 2014-2019, with an APC of +0.4591% (p &lt; 0.000001). Conclusion: The prevalence and incidence of T1DM among people aged 15-39 increased significantly between 1990 and 2021, with a greater increase in males. This highlights the need for gender-specific strategies in T1DM prevention and management, and research into the factors driving these disparities. Presentation: Sunday, July 13, 2025

Multiple myeloma (MM) treatment outcomes in developing countries may be impacted by resource constraints. This systematic review and meta-analysis evaluated efficacy outcomes of MM treatments across developing regions. Comprehensive searches in five major databases identified 37 eligible studies from Asia, Africa, Latin America, and Eastern Europe. The Newcastle-Ottawa Scale was used to assess risk of bias. Newer novel agents including daratumumab, carfilzomib, and pomalidomide showed limited use across studies. For patients receiving autologous stem cell transplantation (ASCT), the pooled overall survival rate at longest follow-up (2.5-12.5 years) was 62% (95% CI: 48-75%), with high heterogeneity (I²=92%), while the progression-free survival rate at longest follow-up (3-8 years) was 44% (95% CI: 23-67%). Comparative analyses demonstrated ASCT was associated with significantly superior 5-year survival compared to conventional chemotherapy (RR: 1.59; 95% CI: 1.38-1.82). Bortezomib-based regimens showed better outcomes than thalidomide-based therapies (HR for overall survival (OS) at 4 years: 0.73; 95% CI: 0.53-1.0) and alkylating agent-based regimens (HR: 0.48; 95% CI: 0.28-0.83). Despite resource limitations, ASCT and certain novel agents are associated with improved survival outcomes for MM patients in developing countries. However, substantial heterogeneity in outcomes suggests variability in healthcare infrastructure, treatment accessibility, and clinical expertise across these regions.

406 Background: Anxiety is highly prevalent among oncology patients, often arising from uncertainty around diagnosis, treatment options, and prognosis. Elevated anxiety can impair decision-making, reduce treatment adherence, and diminish overall quality of life. Effective second opinion consultations may help mitigate anxiety and increase patients’ confidence in recommending healthcare services to others. Our study evaluates the impact of oncology second opinion (OSO) consultations on anxiety level (AL) and confidence in the organization (CIO) providing the second opinion, i.e., Cincinnati Cancer Advisors (CCA) and Naples Cancer Advisors (NCA). Methods: The study included patients with cancer diagnoses, age ≥18 years, who were served in person for OSO at CCA and NCA. A survey was used before and after consultation, measuring AL (scale 1- 10) and CIO level (scale 1 - 10), assessed by asking patients how likely they would refer loved ones to the organization. After the content and face validation, patients completed the survey anonymously, put it in a sealed envelope, and dropped it in a dedicated box. Data was analyzed using paired t-tests to compare the change from pre- to post-consultation scores. Spearman’s correlation test was used to assess the relation between the changes in AL and CIO. Statistical significance was assessed using an alpha-level of 0.05. Analyses were conducted via R and R Studio (version 2025.5.1.513). Results: Overall, 46 consecutive patients participated (45 completed AL pre and post visit survey and 43 completed the CIO pre and post visit survey). The mean pre-consultation anxiety score was 5.92 (SD = 2.58), and the post-consultation score was 3.87 (SD = 2.10), demonstrating a significant reduction (mean paired difference = -2.05; p < 0.0001). The mean pre-consult CIO was 8.21 (SD = 2.03), increasing to 9.73 post-consultation (SD = 0.53), indicating a significant improvement (mean paired difference = 1.66; p < 0.0001). The correlation between changes in AL and CIO was not statistically significant, which may be attributed to the high baseline CIO scores (ceiling effect) and the small sample size. Conclusions: Oncology second opinion was associated with a marked decrease in patient AL and a significant increase in CIO. The patient survey will continue to recruit additional participants to increase the sample size and explore the correlation between changes in AL and CIO. Studying the downstream impact on patient experience and outcome is warranted.

AbstractElectronic patient-reported outcome measures (ePROMs) can improve care for people with cancer, but effectiveness hinges on well-supported integration in clinical settings.We evaluated clinician use of specific clinical decision support (CDS) tools in the electronic health record (EHR) designed to facilitate timely, clinically appropriate responses to ePROM scores for six symptoms commonly experienced by cancer patients.The parent pragmatic trial, which took place at Mayo Clinic (Rochester, Minnesota, United States) and its affiliated community health care system between March 2019 and January 2023, evaluated the population-level effectiveness and implementation of an ePROM surveillance and EHR-facilitated collaborative care symptom management intervention. The present evaluation used a case study approach with four data sources: (1) clinician interactions with CDS tools abstracted from the EHR; (2) clinician notes identified with an institution-specific textual search tool; (3) qualitative interviews and group discussions with care teams; and (4) administrative records reviewed to identify training and outreach to care teams.EHR metrics showed very low adoption of CDS tools including alerts and symptom-specific order sets, despite educational outreach and information technology support provided to clinical care teams. Qualitative findings revealed that CDS use was not easy to integrate into busy clinical workflows and highlighted clinician perceptions that the collaborative care intervention provided additional patient support that reduced clinicians' need to utilize CDS tools. They also highlight the importance of contextual factors, including institutional priorities and EHR changes.This pragmatic clinical trial case study found limited adoption of EHR CDS tools that had been developed to increase clinicians' awareness of and responses to ePROM data. Findings suggest the need to align clinician and organizational implementation strategies, simplify CDS tools to fit practice expectations, and identify and address contextual factors that could undercut strategies like education and peer support. This may be especially important for teams who aim to iteratively evaluate and refine CDS and implementation strategies for multicomponent interventions or introduce new strategies that are responsive to barriers while maintaining scalability.

Abstract Introduction Biliary-tract cancers, including intra- and extra-hepatic cholangiocarcinoma and gallbladder carcinoma, are uncommon but highly lethal. They represent roughly 2–3 % of new cancer diagnoses yet contribute about 5 % of cancer-related deaths. Complete surgical resection remains the foundation of curative treatment, whereas the value of peri-operative chemotherapy continues to be debated. Materials and Methods The National Cancer Database (NCDB) was queried for patients diagnosed with non- metastatic biliary tract cancer at age 18 or older between 2004 and 2019. After excluding patients with unknown timing of surgery and chemotherapy, patients who died within 90 days of the most definitive primary site surgery, and patients lost to follow-up, we split the cohort into three groups according to the clinical stage (stage I-III). Then, we evaluated the overall survival (OS) between the different treatment modalities (surgery only, chemotherapy only, adjuvant chemotherapy following surgery, and neoadjuvant chemotherapy followed by surgery) in each group. We studied the OS using Kaplan-Meier estimates and multivariate Cox regression analyses to evaluate factors associated with OS. Results A total of 35,260 patients with non-metastatic biliary tract cancers were included in the analysis, of which 50.4% were females, 83% Caucasians, and 9.5% African Americans. The median age at diagnosis was 70 (range 18-90). 14,757 (41.9%) were stage I, 12,472 (35.4%) stage II, and 8,031 (22.8%) stage III. 7,286 (20.7%) had surgical resection only, 8,144 (23.1%) had chemotherapy only, 6,964 (19.7%) had surgical resection with perioperative chemotherapy, and 12,866 (36.5%) did not receive any treatment. We compared survival between different treatment modalities based on clinical stage. In stage I, patients treated with surgery alone exhibited superior median OS compared with those receiving adjuvant chemotherapy (65.7 vs 50.4 months, P < 0.001). Median OS after neoadjuvant chemotherapy was numerically higher than surgery alone (79.8 vs 65.7 months); however, this difference was not statistically significant (P = 0.63). Whereas in stage II, patients who were treated with adjuvant and neoadjuvant chemotherapy had better mOS compared to those treated with surgery only (33.9 and 40.3 vs 29.9 months with P<0.001 and P=0.005, respectively). The same trend was seen in stage III, patients who were treated with adjuvant and those treated with neoadjuvant chemotherapy had better mOS compared to surgery only (22.6 and 41.5 vs 19.5 months, respectively, with P<0.001 for all). In multivariate analysis, adjuvant and neoadjuvant chemotherapy did not affect the OS in all stages, except in stage III, where neoadjuvant chemotherapy was associated with better OS (HR 0.646, 95% CI 0.530-0.786; P<0.001). Conclusion Adjuvant and neoadjuvant chemotherapy do not seem to have a survival benefit in early-stage (stage I and II) biliary tract cancers, whereas neoadjuvant chemotherapy tends to improve OS in stage III.

Objectives: Anaplastic thyroid cancer (ATC) is a rare and aggressive type of thyroid malignancy with a very poor prognosis and outcome despite therapy. The rarity of this disease and the poor functional status of ATC patients limit the ability to conduct clinical trials, thus there is a lack of large, controlled trials to guide treatment and evaluate the benefit of combined modality therapy. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with ATC at age 18 or older between 2004 and 2018. After excluding patients with unknown number of treatment modalities, Charlson-Deyo score—a weighted summary of 17 chronic disease categories where higher scores denote greater baseline comorbidity burden—of 3 or more and patients lost for follow-up, we split the cohort into 3 groups according to the number of treatment modalities they received. Treatment modalities included surgery, radiation, and systemic therapy. Then, we evaluated the overall survival (OS) between the 3 groups. We studied the OS using Kaplan-Meier estimates and multivariate Cox regression analyses to evaluate factors associated with OS. In addition, propensity score matching (accounting for age, sex, race, Charlson-Deyo score, and clinical M stage) was used for more robust results. Results: A total of 3460 patients with ATC were included in the analysis, of which 1472 (42.5%) either received one type of therapy or did not receive any therapy (group 1), 1092 (31.6%) received bimodal therapy (group 2), and 896 (25.9%) received trimodal therapy (group 3). We found that group 3 had better OS compared with group 1 and group 2 (median OS 9.1 vs. 1.7 and 4.9 mo, respectively, with P <0.001 for all comparisons). Propensity score matching yielded 896 patients in each group. We found that group 3 had better OS compared with group 1 and group 2 (median OS 9.1 vs. 1.9 and 5.2 mo, respectively, with P <0.001 for all comparisons). Same trend was found in subgroup analysis when we split the cohort according to the metastatic status; in M0 group (median OS was 10.4 vs. 1.9 and 6.1 mo, respectively, with P <0.001 for all), in M1 group (median OS was 5.9 vs. 1.4 and 3.7 mo, respectively, with P <0.001 for all). Modality-specific analyses further demonstrated that surgery, radiation, and systemic therapy each independently prolonged OS in both M0 and M1 cohorts (all P <0.001). These individual benefits explain the additive advantage of trimodal therapy and underscore that offering at least one evidence-based modality is preferable when comprehensive treatment is infeasible. On multivariate analysis, group 1 and group 2 were associated with worse OS compared with trimodal treatment (HR: 2.721; 95% CI: 2.466-3.002 and HR: 1.434; 95% CI: 1.299-1.582, P <0.001 for all). Conclusions: Patients with ATC who were treated with intensive trimodal therapy had statistically significant improvement in OS compared with patients who received less intense therapy. This survival benefit was observed in both metastatic and nonmetastatic groups. Although we acknowledge the limitations of this retrospective analysis, our results showed the critical role of an intensive therapy approach in this aggressive malignancy.

Abstract Glioblastoma is the most common type of malignant primary brain tumor and a major cause of morbidity and mortality. In 2021, the World Health Organization updated the classification of Central Nervous System (CNS) tumors to restrict glioblastomas to isocitrate dehydrogenase-wildtype (IDHwt) tumors, improving understanding of the prognosis and optimal therapy for these tumors. This revision also enables more homogeneous populations of patients to be enrolled in clinical trials, facilitating the evaluation of novel therapies. In this updated consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of patients with glioblastoma is discussed. In addition, novel therapies such as immunotherapies, viral therapies, targeted molecular therapies, theranostics, and antibody–drug conjugates will be reviewed, as well as the current challenges and future directions for research.