Citations

Abstract Background Central nervous system (CNS) tumors are a significant cause of morbidity and mortality in sub-Saharan Africa (SSA). To date, no large-scale efforts have focused on brain tumor genetics within this region. This study aimed to assess and map the current neuro-oncology capacity in SSA, including workforce availability and existing services for brain tumor registries and biobanks. The results represent the final analysis representing respondents from 70 healthcare institutions. Methods This cross-sectional study utilized an online survey to collect data from healthcare professionals involved in CNS tumor care across SSA through the Society for Neuro-Oncology SSA (SNOSSA). The survey gathered information on the availability of neuro-oncology practitioners, neuropathology and molecular diagnostic capacity, brain tumor management, cancer registries, and biobanking of specimens. Purposive sampling was used to identify participants, with the questionnaire provided in English, French, and Swahili. Results A total of 145 respondents from 22 countries and 70 healthcare institutions participated. Among the 70 institutions, neurosurgery was available in 89%, anatomic pathology in 74%, and medical oncology in 71%. For radiologic evaluation, 64% of institutions reported having both CT and MRI, while 17% had CT only. Molecular testing through IHC or NGS was available in 46% of institutions. Multidisciplinary tumor boards for CNS cases were present in 86% of institutions. General cancer registries were available in 66% of institutions, while 29% had brain tumor-specific registries, and 10% maintained brain tumor biorepositories. Conclusion This study provides a comprehensive summary of the neuro-oncology capacity in SSA. Next steps are to reach out to institutions who have registries and determine what data are being collected, with the hopes of defining a set of common elements to expand registry efforts across SSA. Similarly, to reach out to institutions that have ongoing brain tumor biobanks and CT/MRI capacity to determine what infrastructure exists.

AbstractAbstract Background Central nervous system (CNS) tumors are a significant cause of morbidity and mortality in Sub-Saharan Africa (SSA). This project aimed to assess and map out the current neuro-oncology capacity in SSA, brain tumor registries, and biobanks. Methods This cross-sectional study utilized an online survey to gather data from healthcare professionals involved in CNS tumor care across SSA through the Society for Neuro-Oncology SSA (SNOSSA). The survey captured information on the availability of neuro-oncology practitioners, neuropathology, molecular diagnostics, cancer registries, and biobanking. Results A total of 145 respondents representing 70 healthcare institutions across 22 countries participated. Of the 70 institutions, specialties included neurosurgery (89%, 62/70), anatomic pathology (74%, 52/70), and medical oncology (71%, 50/70). For radiologic evaluation, 64% (45/70) of responding institutions reported having both CT and MRI. Access to molecular testing through immunohistochemistry or next-generation sequencing was available in 46% (32/70) of responding institutions. Multidisciplinary tumor boards were available for CNS cases in 86% (60/70) of responding institutions. Brain tumor-specific registries were available in 29% (20/70) of responding institutions, and 10% (7/70) maintained brain tumor biorepositories. Conclusion This study demonstrates that SSA has substantial potential in neuro-oncology care practice capacity and facilities. The most significant gaps were in neuropathology and molecular testing, which makes widespread implementation of the WHO 2021 diagnosis challenging. Understanding the prevalence of CNS tumor subtypes in SSA is difficult due to the low number of brain tumor registries and biobanks.

Background: Variable terminology is used in the literature to describe facial synkinesis and hypertonicity following incomplete recovery from facial paralysis and its associated medical and surgical treatments. Study Objectives: Establish a nomenclature consensus for this condition among a group of facial nerve experts. Design Type: Consensus study. Methods: Using modified Delphi methodology, an international, multidisciplinary group of facial nerve experts reviewed the terminology for the name of the clinical condition and treatments of interest. Online surveys and a virtual discussion were performed to establish consensus, defined a priori as agreement by 80% of the group. Results: Twenty-five facial nerve experts established consensus after three Delphi rounds. Consensus terminology for the condition is “facial synkinesis” with 84% agreement. Medical treatment is termed “chemodenervation” with 100% agreement. Surgical treatments including “selective facial neurectomy,” “selective facial neurotomy,” “selective facial myectomy,” and “selective facial myotomy,” were defined and reached agreement of 100%. Conclusions: This international group of facial nerve experts has recommended standardized nomenclature for the condition of facial synkinesis and its various treatments. While “facial synkinesis” reached consensus as the preferred term, some experts noted it may insufficiently describe the full clinical spectrum, which includes muscle hypertonicity, weakness, and spontaneous twitching.

Context.— Complexity of ordering and transfusing blood is particularly evident in the pediatric population. Simplification, clarification, and standardization of blood orders can decrease complexity and improve patient safety. Objective.— To improve patient safety by optimizing electronic ordering of blood components in pediatrics through a collaborative process improvement initiative. Design.— A multidisciplinary working group, formed as part of a value stream analysis to improve transfusion safety at Children’s Healthcare of Atlanta (Atlanta, Georgia), focused on decreasing variability and providing clarity when ordering, preparing, and transfusing blood using the electronic health record. Through benchmarking with other pediatric institutions and a collaborative design process with multiple local stakeholders, an extensive redesign in the existing orders and order sets occurred. Metrics were collected to determine if a change was an improvement. Results.— Nurse and laboratory informaticists, a pathology informaticist, and a transfusion medicine specialist built the new orders based on the design. The new orders focused on the following changes: standardization, introduction of logic, naming conventions, clarifying definitions, adding calculations, improving transparency of history and laboratory data, removing aliquots, clarifying communication, and implementing additional modules to inform the provider of necessary information about the patient. Metrics included a decrease in the number of orders changed within an hour, decreased calls from the blood bank to the provider to clarify the order, and an absence of overtransfusions and transfusion-related serious safety events for a year following implementation. Conclusions.— This collaborative initiative, using standard process improvement tools, resulted in standardized blood orders improving transfusion safety.

Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease (NAFLD), is a growing but often unrecognized medical problem for people with diabetes (particularly type 2 diabetes, especially when associated with obesity). Liver health has not been at the forefront of complications tracked for disease prevention, as traditionally done for diabetic retinopathy, nephropathy, or neuropathy. However, liver steatosis affects approximately two out of three people with type 2 diabetes and places them at an increased risk for metabolic dysfunction–associated steatohepatitis (MASH), cirrhosis, hepatocellular carcinoma (HCC), and overall liver-related mortality. MASLD is also associated with extrahepatic cancers, atherosclerotic cardiovascular disease, and progression from prediabetes to type 2 diabetes and negatively impacts health-related quality of life. However, most individuals and their health care professionals remain unaware of the severe hepatic or extrahepatic health risks associated with MASLD and the need for early identification. In recognition of this knowledge gap and the rising prevalence of MASLD, this consensus report is a call to action to screen for liver fibrosis and risk stratify people with prediabetes or type 2 diabetes, in particular if obesity is also present. This consensus report explains the rationale for the recent MASLD nomenclature change, how to best risk stratify, current treatment and long-term monitoring options, the value of an interprofessional approach to disease management, and the impact of alcohol intake on liver health. More awareness about the health risks associated with MASLD and broad adoption of screening for liver fibrosis as a new standard of care hold promise for a future without cirrhosis for people with prediabetes and type 2 diabetes.

ABSTRACTA core tenant of the Geriatric Emergency care Applied Research Network 2.0—Advancing Dementia Care (GEAR 2.0‐ADC) is the inclusion of community members during all stages of clinical research. As such, we deliberately integrated and supported patient and public involvement in the evaluation and selection of GEAR 2.0‐ADC Pilot Research Grants by developing and adapting traditional grant application review structures, with input from community members, to create the GEAR 2.0‐ADC Community Review Committee approach. Community members, including persons living with dementia, effectively participated in all three rounds of research grant application review and selection, complementing the traditional scientific review process. The structure and flexibility of the GEAR 2.0‐ADC Community Review Committee approach serve as a model for patient and public grant application review involvement with strong potential for applications across grant reviews in other medical specialties.

Abstract Introduction: Heme-binding biguanides inhibit cytochrome P450 monooxygenase-mediated biosynthesis of the epoxy fatty acid (EpFA) (±)14,15-EET, which promotes progression of ER+HER2- breast cancer as well as regulatory T cell (Treg) proliferation. However, there are no known strategies to exploit this vulnerability. Metformin has shown promise but lacks sufficient potency and clinical utility. Through structure-based design, heme binding hexyl cubane derivatives of metformin were identified, which potently inhibited (±)14,15-EET biosynthesis. Fluorination of the hexyl moiety improved pharmacokinetics (PK) and reduced toxicity. Among the fluorinated derivatives, C5F2-HCB potently inhibited (±)14,15-EET biosynthesis (IC50=3.1 uM for C5F2-HCB vs. 5 mM for metformin). C5F2-HCB and metformin are candidate agents for TME activation from “cold” to “hot” due to their inhibition of EETs biosynthesis and EET-driven oxidative phosphorylation (OXPHOS) which promotes tumor hypoxia. We then tested whether C5F2-HCB or metformin could inhibit immune exclusion in the immunologically “cold” ovarian dependent STAT1 KO SSM2ucd mammary carcinoma model, in part, by reducing Tregs and/or increasing CD8 or CD4 tumor infiltrating T cells (TIL). We hypothesized that biguanides, by reducing EETs, would suppress Tregs and promote effector T cells in the TME. We also hypothesized that C5F2-HCB would be more effective than metformin in modulating the TME, based on greater potency for inhibition of (±)14,15-EET biosynthesis. Both biguanides were tested at their maximum tolerated dose (C5F2-HCB; 18 mg/kg daily and metformin; 50 mg/kg every other day). Results: In the SSM2ucd allograft, all combination treatment groups with biguanides reduced tumor growth relative to the IgG control at the endpoint (day 63) : metformin + IgG (51.5±9.8% of control), C5F2-HCB + IgG (53.3±12.8%), metformin + anti-PD-1 (50.4±11.5%), and C5F2-HCB + anti-PD-1 (49.6±12.8%) [(P < 0.05) for all comparisons]. In contrast, anti-PD-1 antibody alone failed to reduce tumor growth at the endpoint. Flow cytometry analysis of the TME revealed that only C5F2-HCB + IgG treatment increased CD8+ tumor-infiltrating lymphocytes (TILs) compared to all other treatment groups (>2-fold; P < 0.05). Additionally, only C5F2-HCB + anti-PD-1 reduced intratumoral Tregs (>3-fold; P < 0.05). C5F2-HCB in combination with IgG or anti-PD-1 reduced intratumoral macrophages by >50% (P < 0.001) and reduced the M2/M1 macrophage ratio by 32-61% (P < 0.05) relative to other groups. No effects on CD4+ T cells were observed. Furthermore, C5F2-HCB and IgG or anti-PD-1 increased intratumoral neutrophils by 75- 120% compared to the anti-PD-1 or IgG (P < 0.05). (Multiple comparisons tested by ANOVA). Conclusion: Relative to IgG alone, C5F2-HCB and metformin inhibited growth of the SSM2ucd allograft in combination with either anti-PD1 or IgG. In contrast to metformin, only C5F2-HCB modulated the TME, including increased CD8+ TILs with IgG, reduced Tregs with anti-PD-1, and decreased M2/M1 macrophage ratio with IgG and anti-PD-1. C5F2-HCB, in contrast tometformin, was effective in modulating an immune excluded TME and may contribute to a strategy for clinical translation. Citation Format: Zhijun Guo, Jianxun Lei, Joshua McCarra, Qing Cao, Michael J. Pryzbilla, Brenda Koniar, Beverly Norris, Robert J. Schumacher, Swaathi Jayaraman, John R. Hawse, Antonino B. D'Assoro, Ilia G. Denisov, Stephen G. Sligar, Kathryn L. Schwertfeger, Michael A. Farrar, Dipak Panigrahy, Hammock D. Bruce, Elizabeth A. Ambrose, Gunda I. Georg, Goetz P. Matthew, David A. Potter. C5F2-hexyl-(cuban-1-yl-methyl)-biguanide (C5F2-HCB) overcomes an immune excluded tumor microenvironment (TME) and suppresses tumor growth in the ovarian dependent ER+HER2- SSM2ucd mammary carcinoma allograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB010.

109 Background: C and Lu are associated with overall survival benefit and approved for pts with mCRPC after prior treatment with docetaxel and an androgen receptor pathway inhibitor (ARPI). However, in real-world settings, administering Lu requires coordination across specialties and resources [PMID: 36637862], which could delay its administration. Herein, we sought to compare the time from medication order to administering the first dose of C versus Lu. Methods: This study used pt level data from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Inclusion criteria: availability of the date of the first order of single-agent C or Lu and the date of first administration of the drugs. The time between the first medication order to the administration of single-agent C or Lu was measured. Wilcoxon rank-sum test was used to compare the median days between medication order to administration between these 2 agents and a stratified analysis by practice type and insurance was performed. Results: Of 2,329 orders, 2,045 orders were for C between 1/1/2013 and 1/26/2024, while 284 were for Lu between 8/1/2013 and 12/6/2023. The time from medication order to administration was significantly longer with Lu (median 22 days, IQR 12-43) compared to C (median 7 days, IQR 3-14, p < 0.001). Time from medication order to administration of C and Lu by practice type and insurance is summarized (Table). At the time of the first order, pts in Lu cohort, compared to C cohort, were significantly older (median age 74 vs. 72, p < 0.001), more likely to be treated at an academic practice (27% vs. 15%, p < 0.001), and more likely to be covered by a commercial health plan (80% vs. 73%, p < 0.001). Conclusions: Our results show that it takes significantly longer to administer Lu compared to C across different practice types and most insurance plans. These results could inform healthcare policies aimed at improving access to Lu and guide treatment selection in the clinic. Time from medication order to administration of C and Lu by practice type and insurance. Category Subtype (number of orders for C/number of orders for Lu) CN = 2045 LuN = 284 p-value Practice type, mean (range) (days) Academic (315/77) 1.3 (0 – 59) 9.2 (0 – 55) < 0.001 Community (1730/207) 13 (0 – 243) 44 (1 – 282) < 0.001 Insurance, mean (range) (days) Commercial (1494/226) 11 (0 – 163) 32 (0 – 215) < 0.001 Medicare/other government programs (266/46) 10 (0 – 120) 46 (0 – 282) < 0.001 Medicaid (32/2) 9 (0 – 76) 28 (0 – 55) 0.8 Others (72/6) 12 (0 – 42) 21 (0 – 41) 0.2 Unknown (181/4) 14 (0 – 243) 76 (39 – 91) < 0.001

104 Background: Androgen deprivation therapy (ADT) intensification [ADT + androgen receptor-pathway inhibitor (ARPIs) +/- docetaxel] has been shown to improve survival outcomes in pts with mHSPC and is recommended as standard of care by all major guidelines. However, prior studies have shown underutilization of ADT intensification [PMID: 39191549]. There are limited updated and large-scale studies on the use of ADT intensification, beyond January 2023. In this study, we aimed to assess the treatment patterns of ADT intensification in real-world pts with mHSPC in the US, including data on those treated since January 2023. Methods: This retrospective study utilized the nationwide Flatiron Health Electronic Health Record (EHR) derived de-identified database. Eligibility: Pts diagnosed with mHSPC and availability of treatment information (ADT and/or line of therapy in mHSPC). The data cut-off date was 5/31/2024. Treatment patterns were summarized using frequency and percentages. All analysis was done using R version 4.2.3. Results: Among 24,105 pts with metastatic prostate cancer in the database, a total of 14,084 were eligible and included. The median age at metastatic diagnosis was 72 years (IQR 65 – 79), and 60% were White non-Hispanic. In the overall cohort (1/1/2013–5/15/2024), 56.8% received ADT monotherapy, and 37.7% received ADT intensification. Table summarizes the treatment patterns by year, highlightinga consistent increase in adoption of intensified ADT regimens, and a decline in use of ADT monotherapy. Notably, since January 2023, 76.8% pts with mHSPC received ADT intensification while only 17.3% of pts received ADT monotherapy. Conclusions: To our knowledge, this is the first and largest study to evaluate the current use of ADT intensification. These data indicate a notable improvement in the adoption of level 1 evidence (ADT intensification) in the treatment of pts with mHSPC. These encouraging data emphasize the benefits of continued efforts to promote guideline-concordant care and provide the current treatment landscape to design clinical trials. Treatment patterns by year in pts with mHSPC. Treatment 2013–2017n = 5,263(%) 2018n = 1,313 (%) 2019n = 1,407(%) 2020n = 1,353(%) 2021n = 1,483(%) 2022n = 1,556(%) 2023n = 1,459(%) 2024n = 250(%) ADT monotherapy 4,095 (77.8) 856 (65.2) 819 (58.2) 664 (49) 698 (47.1) 569 (36.6) 291 (20) 5 (2) ADT + ARPI 155 (2.9) 238 (18) 354 (25.1) 452 (33) 555 (37.4) 695 (44.7) 842 (58) 154 (61.6) ADT + Docetaxel 709 (13.5) 156 (12) 175 (12.4) 156 (12) 134 (9.0) 117 (7.5) 78 (5.3) 19 (7.6) Triplet(ADT + ARPI + Docetaxel) 6 (0.1) 2 (0.2) 1 (0.1) 2 (0.1) 9 (0.6) 82 (5.2) 166 (11.1) 53 (21.2) Other therapies 298 (5.7) 61 (4.6) 58 (4.1) 79 (5.8) 87 (5.9) 93 (6) 82 (5.6) 19 (7.6)