Citations

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. M. Filal: None. A. Ullah: None. M.U. Hussain: None. M.A. Sadiq: None. T. Asghar: None. F. Arshad: None. N.K. Binashikhbubkr: None. H. Jawad: None. A. Abdullah: None. M. Qadri: None. A. Qadeer: None. M. Khawar: None. H. Ahmad: None. F. Ahmed: None. R. Alcaraz: None. Background: Hypertension is a major global health issue, affecting nearly half of U.S. adults. It is a leading risk factor for cardiovascular diseases like stroke, heart attack, and heart failure. Additionally, it is often linked to endocrine disorders, which can result in secondary hypertension. Endocrine disorders contributed to a concerning 2,383,332 deaths in the United States between 1999 and 2020, with many of these individuals having underlying hypertension. Methods: Death certificate data for adults aged 25 and older were obtained from the CDC-WONDER database. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMRs) per 100,000 individuals were computed. Temporal trends were analyzed by calculating the annual percent change (APC) and the average annual percent change (AAPC) in the rates using Joinpoint regression analysis. Results: The age-adjusted mortality rate (AAMR) rose sharply from 10.7 (95% CI:10.6-10.9) in 1999 to 24.9 (95% CI: 9.5 to 56.7) in 2001, then continued to increase steadily to 36.5 (95% CI: 0.6 to 2.1) by 2018. From 2018 onwards, the rate spiked significantly, reaching 51.7 (95% CI: 9.3 to 23.5) in 2020, which coincided with the COVID-19 pandemic. Men had higher overall AAMR i.e. 36.6 as compared to women 28.4 during the span of this study. Stratifying by race, Non-Hispanic Blacks or African Americans had the highest overall age-adjusted mortality rate at 64.4 vs non-Hispanic whites, who had the lowest rate at 27.6. Southern states exhibited the highest mortality rates among the census region followed by the Western, Midwestern, and Northeastern regions. In contrast, the Annual Mortality Rates (AAMRs) displayed similar patterns across all regions. Regarding age, people aged 85 and above had the highest mortality rate among all the age groups while ages 25-34 had the lowest. Conclusion: Endocrine disorders associated with underlying hypertension showed an increasing trend throughout the study period, peaking during the COVID-19 pandemic. These findings account for immediate targeted interventions directed at the most vulnerable demographic and geographical groups Presentation: Monday, July 14, 2025

Abstract Disclosure: R. Haider: None. M. Waqas: None. S. Khan: None. A. Ullah: None. M. Khawar: None. A. Qadeer: None. M. Talha: None. A. Batool: None. A. Khan: None. M.Z. Haider: None. R.W. Kirchoff: None. Background: Hypothyroidism and heart failure (HF) contribute significantly to mortality among older adults. Understanding mortality trends, including demographic, geographic, and socio-economic disparities, is crucial to inform healthcare policies and resource allocation. Methods: This study analyzed age adjusted mortality rates (AAMRs) from 1999 to 2022 for adults aged 55-85+ years. Age adjusted mortality rates (AMRs) per 1,000,000 population were stratified by gender, race, geographic location, and urbanicity. Trends were evaluated using Average Annual Percentage Change (APC) with 95% confidence intervals (CI), examining periods of decline and increase. Results: Between 1999 and 2022, 105,008 deaths were recorded among older adults (55-85+ years) due to hypothyroidism and heart failure (HF). The age-adjusted mortality rate (AAMR) initially declined from 1999 to 2016, marked by a significant drop between 2005 and 2008 (APC = -6.0, 95% CI: -7.6 to -3.0). However, mortality trends reversed post-2016, with a sharp increase (APC = 6.7, 95% CI: 5.5 to 8.4). Age-specific trends revealed declining crude mortality rates (CMR) across all groups until 2016, followed by increases, particularly in the 65-74 and 75-84 age brackets, with APCs of 14.1 (95% CI: 7.8 to 27.8) and 8.9 (95% CI: 3.8 to 21.8), respectively. Gender disparities showed men and women had similar trends, with declines until 2015-2016 followed by surges, with APCs of 6.8 (95% CI: 5.2 to 9.1) and 6.6 (95% CI: 4.6 to 11.1), respectively. Racial disparities highlighted steady declines until 2016, followed by increases in non-Hispanic Whites (APC = 10.4, 95% CI: 5.2 to 23.2) and Hispanics (APC = 7.5, 95% CI: 6.0 to 10.1). Geographically, the Midwest exhibited the highest AAMR (71.1), while the Northeast showed the lowest (51.4). State-level disparities revealed North Dakota with the highest AAMR (129.5), contrasting with Nevada, which had the lowest (20.4). Urban-rural differences showed similar trends, with notable AAMR increases in both settings post-2016. These results underscore significant demographic and regional disparities in hypothyroidism and HF-related mortality. Conclusion: While mortality from hypothyroidism and HF among older adults declined until 2016, trends have since reversed across all demographic and geographic strata. Addressing these rising rates require targeted interventions focusing on high-risk groups and areas. Presentation: Monday, July 14, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. F. Saleem: None. A. Ullah: None. M. Shah: None. A. Qadeer: None. M. Khawar: None. H. Jawad: None. H. Ahmad: None. F. Ahmed: None. S. N.l.: None. R. Alcaraz: None. Background: Diabetes mellitus (DM) is a global health burden, contributing significantly to mortality and comorbidities, including chronic kidney disease (CKD), which remains a leading cause of morbidity and mortality, especially in type 1 and type 2 diabetes. Methods: This retrospective cohort study examined mortality data from the United States from the CDC WONDER database, which gathers data from death certificates. Particularly, deaths from renal problems (ICD-10 codes E10.2-E14.2) linked to diabetes were the emphasis. Sex, age, race/ethnicity, and geographic location were among the important demographic factors that were used to stratify the data for the analysis. Temporal trends were examined using linear regression, while geographic disparities were assessed through chi-square tests and regression analysis. A significance level of p<0.05 was used for all tests. Results: According to the data, the death rate from diabetes increased significantly between 1999 and 2020. Between 1999 and 2020, the number of deaths from diabetes rose from 2,325 to 74,296. From 13.12 per 100,000 in 1999 to 276.92 per 100,000 in 2020, the age-adjusted death rate increased significantly, indicating a fivefold rise in mortality rates over the 21 years. After 2010, the pace of increase became especially steep, with notable yearly increases, especially in the years after 2013. In the Hispanic population alone, the number of deaths from diabetes more than quadrupled between 2013 and 2020, rising from 5,378 in 2013 to 10,395 in 2020. Male mortality rates were consistently greater than female death rates, indicating gender-based inequities as well. By 2020, there were 41,225 male deaths from diabetes (AAMR: 351.07). Notably, the death rate for men was almost 60% greater than that for women in 2020, with rates rising more sharply for men, particularly from 2010 onward. Significant differences in diabetes-related mortality were also observed by geography. Florida, Texas, and California had the largest mortality burdens; in California alone, 73,185 deaths, or 13.8% of all deaths, occurred. Lastly, more deaths were found to occur in medical facilities, especially inpatient settings, as well as at home or in hospice care, indicating a change in the place of death. Conclusions: The study shows a significant rise in diabetes-related mortality in the US over the past two decades, with males experiencing a higher mortality rate. Geographic disparities are also evident, with Southern states and large states like California, Texas, and Florida contributing disproportionately. The shift in death places suggests increased reliance on medical facilities, home care, and hospice care. The study calls for targeted public health interventions to address the growing burden of diabetes-related mortality, particularly in high-risk regions. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. F. Saleem: None. M.H. Alsaadi: None. H. Jawad: None. A.Z. Khan: None. A. Qadeer: None. M. Khawar: None. A. Ullah: None. M.F. Hemida: None. H. Ahmad: None. F. Ahmed: None. R. Alcaraz: None. Background: Globally, pediatric endocrine anomalies are a significant cause of early mortality. This study examines the discrepancies of paediatric endocrine abnormalities across various demographic and geographic groups in the United States, including gender, census region, race, age groups, and urbanization levels. Our objective was to identify disparities and trends to inform targeted interventions for the vulnerable demographics. Methods: Adhering to STROBES criteria, we extracted the mortality statistics due to endocrine disorders in the paediatric population from 1999-2020 from the Centre for Disease Control and Prevention-Wide Ranging Online Data for Epidemiologic research (CDC-WONDER). We calculated Age-Adjusted mortality rates (AAMRs) per 100,000 individuals. We calculated the Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC) to assess trends stratified by age, gender, urbanization, race, census region, and states. Joinpoint regression model was used for analysis. Results: Between 1999 and 2020, 5161 deaths among children less than 1 year to 14 years of age in the United States were related to endocrine-related disorders. Most occurred due to thyroid disorders, diabetes mellitus, and other miscellaneous disorders related to glucose regulation and pancreatic internal secretion. The overall AAPC for endocrine-related mortality in the pediatric population increased from 1.4866 in 2008 to 2.4982 in 2020, with an AAPC of 0.1346 (95% CI: -3.1216 to -3.5003, p > 0.000001). The male population had higher AAPCs than the female population (women: -0.9938; men: 0.7223). There were notable racial differences: The Hispanic or Latino population had the highest AAPC (0.15), followed by the Black population (-0.195) and then the White population with the lowest AAPC (-0.166). According to the age group stratification, the age group with the highest AAPC was the 5-14 age group (2.03) and the lowest the less than 1 year age group, with AAPC (-2.007). There was a significant decrease in deaths in the less than 1 year age group from 1999 to 2020 (p value < 0.05) with APC (-2.0) (95% CI: -3.0191 to -0.9861) and for the 5-14 age group from 2010 to 2020 with APC (10.8861) (95% CI: 3.4843 to 18.8). Depending on the urban-rural categorization, metro areas had a higher AAPC (0.1508) compared to the non-metro areas with an AAPC (-0.4467). Conclusion: The overall decline in endocrine-related deaths in the pediatric population from 1999 to 2020 hails an improvement in efforts made to manage these disorders. However, the recent uptick in the Hispanic-Latino population emphasizes the necessity for targeted efforts to tackle these disparities and improve the health outcomes of affected communities as well as in children 1-4 years of age, depicting the increased vulnerability and need for added care in this age group. Presentation: Saturday, July 12, 2025

Abstract Disclosure: M. Kakakhel: None. F. Saleem: None. A. Ullah: None. K. Abdul Rehman: None. M.H. Alsaadi: None. H. Ahmad: None. A. Qadeer: None. R. Haider: None. M. Khawar: None. H. Jawad: None. J. Ikram: None. M. Filal: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Thyroid disorders are common endocrine disorders including thyrotoxicosis, thyroiditis, hypothyroidism, and autoimmune thyroid diseases. Although it affects an estimated 200 million people globally, the epidemiology of this condition remains underexplored. Here we aimed to investigate mortality trends attributable to thyroid disorders in the US stratified by year, sex, race, and region. Methods: Using data from the CDC WONDER database, we calculated the crude and age-adjusted mortality rates (AAMRs) per 1,000,000 individuals (≥25 years) and used Joinpoint regression to determine annual and average annual percent change (AAPC) in the mortality trends. Results: Between 1999 and 2020, 561,089 deaths were recorded among patients with thyroid disorders in the United States, with an overall increasing trend in mortality (AAPC = 0.78). The age-adjusted mortality rate (AAMR) declined gradually from 1999 to 2018 (APC = -0.43, 95% CI: -0.65 to -0.22) before rising sharply from 2018 to 2020 (APC = 13.05, 95% CI: 6.39 to 20.12). Females had a higher AAMR (139.75) than males (81.99). Among racial and ethnic groups, Whites exhibited the highest AAMR (124.09), followed by American Indian or Alaskan Natives (121.36), Hispanics (89.13), Black or African Americans (88.44), and Asian or Pacific Islanders (59.36). Regional disparities showed the highest AAMR in the Midwest (130.45) and the lowest in the South (109.40). West Virginia (199.93) and North Dakota (198.82) reported the highest state-level AAMRs, while Nevada (60.18) and Florida (65.49) had the lowest. Non-metropolitan areas experienced higher mortality rates (141.04) than metropolitan areas (112.21), underscoring significant geographical and demographic variations in thyroid disorder-related mortality. Conclusion: Adults in the US have shown a rising trend in Thyroid-related deaths, with the highest mortality rates seen in females, Whites, and people living in the Midwest and Non-metropolitan areas. Our study also highlights the disparities across different demographics. Policy makers should focus on equitable access to healthcare to control this increasing mortality. Presentation: Monday, July 14, 2025

Abstract Background: [212Pb]VMT-a-NET is an alpha therapy agent targeting somatostatin receptor subtype 2 (SSTR2)-expressing tumors. Neuroendocrine tumors (NETs) generally express SSTR2 on their cell surface. Here, we report the results of a prospective, open-label, Phase I/IIa clinical trial evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of [212Pb]VMT-a-NET [NCT05636618]. Methods: The study design follows a Bayesian dose-finding algorithm. Main inclusion criteria include histologically proven well-differentiated unresectable or metastatic NETs, radiological evidence of progression on at least one prior line of systemic therapy, demonstration of lesional SSTR2 expression on an FDA-approved SSTR PET. Main exclusion criteria include: prior treatment with systemic PRRT-based therapies. In the dose finding phase, participants can receive up to four cycles of [212Pb]VMT-a-NET at the assigned dose level. Participants are followed for dose-limiting toxicity (DLT) observation up to 42 days after the first cycle. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Here we report safety and preliminary efficacy data of participants enrolled in cohorts 1 and 2 at 92.5 MBq [2.5 mCi] and 185 MBq [5 mCi], respectively. Results: As of 30-Apr-2025 (data cut-off – DCO), a total of 42 participants were enrolled into the study. Nine of them were followed for DLT observation; thirty-three (33) additional participants were subsequently enrolled into cohort 2 to further evaluate safety and efficacy at the selected dose. For data analysis purposes, participants were divided into two different groups: a safety group and an efficacy group. The safety group included all participants enrolled by the DCO (n=42), while the efficacy group included only nine participants enrolled in cohort 1 (n=2) and cohort 2 (n=7) for DLT observation. Median follow up time for participants included in the safety group was 14 weeks (range:0,77); median follow up time for participants included in the efficacy group was 56 weeks (range: 6,77). In the safety group (n=42) we did not observe any DLTs, any grade 4 or 5 adverse events (AEs), any treatment-related discontinuations, any serious renal complications or myelosuppression, or any dysphagia. In the efficacy group (n=9) seven out of nine participants were with no progression as of the DCO, and four out of the seven participants enrolled in cohort 2 achieved a partial response (PR). Three PRs were confirmed, while one was pending confirmation at the time of DCO. Cohort 3, at a dose level of 222 MBq [6 mCi], has recently been opened for enrollment. Safety data for all treated participants and efficacy results for a mature subset will be presented at the congress. Conclusions: [212Pb]VMT-a-NET showed a favorable safety profile and promising clinical benefit for patients with advanced SSTR2-expressing NETs treated at the dose level of 185 MBq (5 mCi). The study is ongoing with cohort 3 currently open for enrollment. Citation Format: Vikas Prasad, Richard Wahl, Lilja Solnes, Savitha Balaraman, Gregory Sibley, Lowell Anthony, Brandon Mancini, Jason Starr, Vineeth Sukrithan, Chih-Yi Liao, Samuel Mehr, Lucia Baratto, Wenjing Yang, Alaa Hanna, Stephen Keefe, Markus Puhlmann, Thorvadur Halfdanarson. [212Pb]VMT-a-NET for somatostatin receptor subtype 2 (SSTR2)-expressing tumors: safety and preliminary efficacy results in patients with advanced neuroendocrine tumors (NETs) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C095 .

Abstract Increased demand to make medical linear accelerator acceptance testing procedures (ATP) more efficient exists while the technology being evaluated for clinical use has become increasingly complex. The most recent American Association of Physicists in Medicine (AAPM) task group giving guidelines to medical physicists on ATP was Task Group report 45, published in 1994. Several new technologies, enhanced machine performance, and possible future changes to ATP since that time require updated guidance from the AAPM. The goal of this task group is to empower the medical physicist to be meaningfully involved with the design and execution of comprehensive and effective linear accelerator ATP beginning with the purchasing contract negotiation to the contractual handover of the linear accelerator to the department for clinical use. Additionally, we discussed aspects related to beam matching, ATP at the time of replacing major linear accelerator's components as well as what we perceive as the future of the ATP process given the trends of standardizing linear accelerators.

Abstract As Alzheimer's disease (AD) research advances, tau has emerged as both a critical biomarker and a promising therapeutic target, central to understanding disease mechanisms, tracking progression, and guiding treatment development. The Fall 2024 Alzheimer's Association Research Roundtable convened experts from academia, industry, National Institutes of Health (NIH), and the United States Food and Drug Administration (FDA) to explore current progress and future directions in tau‐centered diagnostics and therapeutics. Discussions addressed the integration of tau biomarkers into the 2024 Revised Diagnostic Criteria for AD, updates to amyloid and tau positron emission tomography (PET) imaging, and modeling of biomarker trajectories. Presenters highlighted tau‐targeting therapeutics including antisense oligonucleotides, monoclonal antibodies, and small molecules, alongside innovations in drug delivery. The interplay between anti‐amyloid and anti‐tau therapies and strategic design of combination trials were key themes. Regulatory insights facilitated discussions on drug approval pathways. The meeting highlighted the rapid evolution of tau research and emphasized opportunities to improve diagnostics, trial design, and treatment strategies in AD. Highlights The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry, academia, and government, to explore current progress and future directions in tau‐centered diagnostics and therapeutics. Tau has emerged as both a critical biomarker and a promising therapeutic target, central to understanding disease mechanisms, tracking progression, and guiding treatment development. Discussions addressed the integration of tau biomarkers into the 2024 revised diagnostic criteria for AD, updates to amyloid and tau PET imaging, modeling of biomarker trajectories, tau‐targeting therapeutics, and interplay between anti‐amyloid and anti‐tau therapies and strategic design of combination trials.

Stereotactic radiosurgery was associated with a higher obliteration rate compared with embolization in patients with eloquent brain arteriovenous malformations, whereas there was no evidence of a difference in functional outcomes or complications after adjustment.

Abstract The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood. Here, we report a new regulatory link between HELLS and single-strand break (SSB) repair in cellular responses to DNA alkylation damage. We found that loss of HELLS impairs SSB repair and selectively sensitizes cells to DNA alkylating agents and PARP inhibitors (PARPi). Our data reveal non-epistatic interactions between HELLS and PARP1 and suggest that HELLS functionally compensates for PARP1 deficiency in promoting cell survival in response to DNA alkylation damage. Furthermore, we found that HELLS is co-expressed with PARP1 in cancer cells, and its loss is synthetic lethal with homologous recombination deficiency (HRD). This work unveils new functions of HELLS in modulating SSB repair and responses to clinically relevant DNA alkylation damage, thus offering new insights into the potential therapeutic value of targeting HELLS in cancer.