Self-identified Black Patients Research Articles

Abstract 3372: Clinical genetic testing results in metastatic prostate cancer patients

Abstract Background: A proportion of prostate cancers (PCa) are hereditary, driven by likely pathogenic/pathogenic germline variants (PGVs) in DNA repair genes. PGVs in BRCA2 contribute to aggressive prostate cancer biology and overall poorer survival. Genetic testing and targeted sequencing panels help identify PGV carriers who are susceptible to aggressive PCa and may be candidates for targeted therapy with PARP inhibitors. Prior research suggested a high rate of 10-20% of metastatic PCa (mPCa) patients have PGVs in DNA repair genes; however, many of these studies reported highly selected research cohorts. The real-world rate of DNA repair PGVs and whether any genotype-phenotype correlations exist in broader, more racially diverse clinical populations are not well understood. Patients and Methods: We studied two prospective cohorts of males with PCa who presented for genetic testing due to meeting NCCN personal history genetic testing criteria for prostate cancer (metastatic or high risk/very high risk localized). We report PGV frequencies of mPCa patients who underwent genetic testing in a point of care model at the Basser Center within Penn Medicine (Penn-POC, n=596), and a cancer genetics practice at the Corporal Michael Crescenz VA Medical Center in Philadelphia (VA-GT, n = 171). PGVs were identified in ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PMS2, TP53. Results: The Penn-POC and VA-GT cohort included 437 (73.3%) and 59 (34.5%) self-identified white patients, respectively, and 121 (20.3%) and 107 (62.6%) self-identified black patients, respectively. In the Penn-POC and VA-GT cohorts, 7.2% and 7.6% patients were found to carry a PGV, respectively, and 11.9% and 18.1% of patients had variants of uncertain significance (VUS), respectively. The most common PGVs in the Penn-POC cohort were in BRCA2 (2.2%), ATM (1.9%), and BRCA1 (1.3%). The most common PGVs in the VA-GT cohort were in BRCA2 (2.9%), ATM (1.1%), and CHEK2 (1.2%). PGV rates were not statistically different between self-identified white and black patients in either cohort (Penn-POC p= 0.4036; VA-GT p=0. 0.4061). Overall PGV frequencies between the Penn-POC and VA-GT cohorts are not statistically different. There is a correlation between carrier status and age at diagnosis with a significant difference between carriers and non-carriers (p=0.0433) as well as with family history of first degree relatives with PCa (p=0.0184). However, there was not a significant correlation between carrier status and clinical stage at diagnosis, Gleason grade group, or other clinical variables. Conclusions: We report a lower rate of DNA repair PGVs in two prospectively ascertained, racially diverse cohorts of mPCa patients, approximately 7%, compared to the previously reported rates of 10-20%. Our results suggest age and family history, but not other pathological variables are clinical predictors for carrying a PGV in mPCa patients. Citation Format: Taylor Crawford, Emanuel Barrett, Tara Al-Saleem, Maliha Tayeb, Heather Symecko, Caitlin Orr, Vivek Narayan, Samuel Takvorian, Ravi B. Parikh, Yu-Ning Wong, Kyle Robinson, Lisa B. Aiello, Catherine Wolfe, Derek Mann, Kelsey Spielman, Susan M. Domchek, Kara N. Maxwell. Clinical genetic testing results in metastatic prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3372.

Comparison of whole slide image–based deep learning algorithms and genomic classifiers for assessing the risk of prostate cancer metastasis in surgically treated patients.

344 Background: Genomic classifiers improve post-radical prostatectomy (RP) risk stratification compared to conventional clinical-pathologic parameters, but are tissue-destructive and expensive. In contrast, artificial intelligence algorithms utilizing diagnostic hematoxylin and eosin (H&E)-stained slides for risk stratification conserve tissue and could be made widely available at point-of-care. We compared the predictive output of a deep learning-based algorithm applied to H&E-stained whole slide images (WSI) of prostate tumors to commercial genomic classifiers such as Decipher and Prolaris in three diverse RP cohorts with follow-up for metastasis. Methods: We used subsets of three previously published Johns Hopkins RP cohorts with available genomic classifier data. The Natural History Cohort (n=249, Decipher test, PMID: 26058959) and Case-Cohort (n=210, Prolaris CCP test, PMID: 36006048) both utilized a case-cohort design on the outcome of metastasis and consisted of predominantly self-identified White patients, while the Race Cohort (n=93, Decipher test, PMID: 31969336) included only self-identified Black patients with clinical follow-up. For each cohort, a single representative H&E-stained slide from the dominant tumor nodule at RP was scanned. The DL algorithm utilized tumor detection in H&E-stained WSI followed by a classification model to predict metastasis, with or without clinical parameters (age, race, pre-operative PSA, pathologic T- and N-stage, and margin status). The algorithm was trained (n=197) and validated (n=52) on patients from Natural History Cohort and tested on the Race Cohort and Case-Cohort. Harrell’s C-indices based on unadjusted Cox models for time to metastasis were evaluated. Results: The C-index for the WSI-based deep learning algorithm on the Natural History Cohort validation subset was 0.766 (95% confidence interval [CI]: 0.730-0.802) compared to 0.732 (95% CI:0.698-0.766) for the Decipher score. The C-index for WSI-based deep learning algorithm in the Race Cohort was 0.804 (95% CI: 0.790-0.818) compared to 0.724 (95% CI: 0.721-0.726) for the Decipher score. The C-index for the WSI-based deep learning algorithm in the Case-Cohort was 0.840 (95% CI: 0.829-0.851) compared to 0.801 (95% CI: 0.800-0.802) for the Prolaris CCP score. The C-index values for the deep learning algorithm utilizing WSI plus clinical-pathologic parameters were 0.836 (95% CI: 0.796-0.876), 0.882 (95% CI: 0.869-0.894), and 0.890 (95% CI: 0.878-0.901) for the Natural History Cohort, Race-Cohort, and Case-Cohort, respectively. Conclusions: DL algorithms utilizing WSI with or without clinical-pathologic parameters outperform currently employed genomic classifiers for the prediction of metastasis. Validation in additional multi-institutional and racially diverse cohorts is underway.

Abstract C054: Association of fatty acid synthase expression with FASN gene methylation and self-identified race in prostate cancer

Abstract Fatty acid synthase (FASN) catalyzes the synthesis of long-chain saturated fatty acids and is overexpressed during prostatic tumorigenesis; however, the mechanism of this upregulation remains unclear and could include gene amplification, epigenetic regulation or regulation by androgen receptor (AR). Though FASN is an attractive therapeutic target in prostate cancer and several clinical trials of FASN inhibitors are underway, prior studies have suggested racial disparities in FASN copy number and FASN protein expression exist in primary prostate cancer, which may have implications for the therapeutic efficacy of FASN inhibitors. FASN gene amplification may be more common in prostate cancers from self-identified Black (BL) patients than their White (WH) counterparts, and a recent study has suggested that FASN protein expression is also higher among primary prostate tumors from BL compared to WH men due to changes in the AR cistrome. Here, we examine FASN protein expression as measured by digitally quantified immunohistochemistry assay and reverse phase protein array analysis or FASN gene expression, comparing it to gene CpG methylation pattern by InfiniumEPIC profiling and whole genome bisulfite sequencing (WGBS) across multiple racially diverse primary and metastatic prostate cancer cohorts, including more than 1000 tumors. We demonstrate that the FASN gene body is hypomethylated and overexpressed in primary prostate tumors compared to benign tissue. FASN gene methylation shows a significant inverse correlation with FASN protein and gene expression in both primary and metastatic prostate cancer. However, in contrast to previous studies, we find no significant association of FASN expression or methylation with self-identified race or genetic ancestry in models that include ERG gene fusion status across two independent primary tumor cohorts. Taken together, these data support a potential epigenetic mechanism for FASN regulation in the prostate and suggest that FASN inhibitors may be equally efficacious in both BL and WH men with prostate cancer. Citation Format: Oluwademilade Dairo, Lia DePaula Oliveira, Ethan Schaffer, Thiago Vidotto, Adrianna Amaral De Aragao Mendes, Jiayun Lu, Jessica Hicks, Adam G. Sowalsky, Angelo M. De Marzo, Corrine E. Joshu, Brian Hanratty, Karen S. Sfanos, William B. Isaacs, Michael C. Haffner, Tamara L. Lotan. Association of fatty acid synthase expression with FASN gene methylation and self-identified race in prostate cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C054.

Racial Differences in Quality of Life in Patients With Heart Failure Treated With Sodium-Glucose Cotransporter 2 Inhibitors: A Patient-Level Meta-Analysis of the CHIEF-HF, DEFINE-HF, and PRESERVED-HF Trials.

Health status outcomes, including symptoms, function, and quality of life, are worse for Black compared with White patients with heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular mortality and improve health status in patients with heart failure, but whether the health status benefit of SGLT2is is similar across races is not established. The objective of this study was to compare the treatment effect of SGLT2is (versus placebo) on health status for Black compared with White patients with heart failure. We combined patient-level data from 3 randomized clinical trials of SGLT2is: DEFINE-HF (Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure; n=263), PRESERVED-HF (Dapagliflozin in Preserved Ejection Fraction Heart Failure; n=324), and CHIEF-HF (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure; n=448). These 3 United States-based trials enrolled a substantial proportion of Black patients, and each used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to measure health status at baseline and after 12 weeks of treatment. Among 1035 total participants, selecting self-identified Black and White patients with complete information yielded a final analytic cohort of 935 patients. The primary endpoint was KCCQ Clinical Summary score. Twelve-week change in KCCQ with SGLT2is versus placebo was compared between Black and White patients by testing the interaction between race and treatment using multivariable linear regression models adjusted for trial, baseline KCCQ (as a restricted cubic spline), race, and treatment. The data that support the findings of this study are available from the corresponding author upon reasonable request. Among 935 participants, 236 (25%) self-identified as Black, and 469 (50.2%) were treated with an SGLT2i. Treatment with an SGLT2i, compared with placebo, resulted in KCCQ Clinical Summary score improvements at 12 weeks of +4.0 points (95% CI, 1.7-6.3; P=0.0007) in White patients and +4.7 points (95% CI, 0.7-8.7; P=0.02) in Black patients, with no significant interaction by race and treatment (P=0.76). Other KCCQ scales showed similar results. Treatment with an SGLT2i resulted in consistent and significant improvements in health status for both Black and White patients with heart failure.

MP12-03 IMPLICATIONS OF RACE FREE RENAL FUNCTION EQUATIONS ON BLACK PATIENTS WITH RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023MP12-03 IMPLICATIONS OF RACE FREE RENAL FUNCTION EQUATIONS ON BLACK PATIENTS WITH RENAL CELL CARCINOMA Benjamin N. Schmeusser, Arnold R. Palacios, Eric Midenberg, Reza Nabavizadeh, Adil Ali, Dattatraya H. Patil, R. Donald Harvey, Janetta Bryksin, Michael J. Connor, Kenneth Ogan, Mehmet A. Bilen, and Viraj A. Master Benjamin N. SchmeusserBenjamin N. Schmeusser More articles by this author , Arnold R. PalaciosArnold R. Palacios More articles by this author , Eric MidenbergEric Midenberg More articles by this author , Reza NabavizadehReza Nabavizadeh More articles by this author , Adil AliAdil Ali More articles by this author , Dattatraya H. PatilDattatraya H. Patil More articles by this author , R. Donald HarveyR. Donald Harvey More articles by this author , Janetta BryksinJanetta Bryksin More articles by this author , Michael J. ConnorMichael J. Connor More articles by this author , Kenneth OganKenneth Ogan More articles by this author , Mehmet A. BilenMehmet A. Bilen More articles by this author , and Viraj A. MasterViraj A. Master More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003227.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Race is no longer recommended in estimated glomerular filtration rate (eGFR) equations. The resulting lower eGFR may positively impact black patients, such as with earlier nephrology referral and renal transplant eligibility. The impact of race-free equations on black patients with renal cell carcinoma (RCC)–a cohort more likely to experience inferior cancer outcomes–has not been fully examined. Renal function assessment is important in patients with RCC given the recommendations of nephron sparing approaches (i.e. partial nephrectomy [PN]) over radical (RN) in patients with CKDIIIa or estimated post-nephrectomy eGFR of <45 mL/min/1.73m2. Here, we analyze removal of race from eGFR in black patients with RCC and consider the impact of this change in the context of RCC treatment. METHODS: Self-identified black patients undergoing nephrectomy at an academic referral center from 2009-2021 were identified. Patients with end-stage renal disease were excluded. Using preoperative creatinine, height, and weight, eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation with and without race (CKD-EPI-WithRace; CKD-EPI-WithoutRace, respectively), and the Modification of Diet in Renal Disease equation with and without race (MDRD-WithRace; MDRD-WithoutRace, respectively). Distribution of patients and changes within CKD stages with different equations was considered. Subgroup analysis was completed on patients with stage III-IV disease only. RESULTS: 459 self-identified black patients that underwent nephrectomy at our institution were identified, 135 of which had stage III-IV disease. eGFR decreased around 10-13ml/min/1.73m2 with removal of the race coefficient. 13-22%, 6-12%, and 2-3% more black patients would fall under common CKD cutoffs of 60, 45, or 30ml/min/1.73m2, respectively, depending on the equation used (Figure 1). Subanalysis of stage III-IV patients only were similar. CONCLUSIONS: Race free renal function equations may result in significantly more black patients being encouraged to undergo nephron sparing treatments. Source of Funding: We gratefully acknowledge the support of the John Robinson Family Foundation and the Chris Churchill Family Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e133 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benjamin N. Schmeusser More articles by this author Arnold R. Palacios More articles by this author Eric Midenberg More articles by this author Reza Nabavizadeh More articles by this author Adil Ali More articles by this author Dattatraya H. Patil More articles by this author R. Donald Harvey More articles by this author Janetta Bryksin More articles by this author Michael J. Connor More articles by this author Kenneth Ogan More articles by this author Mehmet A. Bilen More articles by this author Viraj A. Master More articles by this author Expand All Advertisement PDF downloadLoading ...

Effect of race-free estimated glomerular filtration rate equations (eGFR) on oncology clinical trial eligibility for Black patients.

611 Background: Race is no longer recommended in estimated glomerular filtration rate (eGFR) equations. The resulting lower eGFR may positively impact black patients, such as with earlier nephrology referral. However, the impact of race-free equations on black oncology patients–a cohort more likely to experience inferior cancer outcomes and underrepresentation in clinical trials–has not been fully examined. Here, we analyze removal of race from eGFR in black patients with cancer, specifically with regards to clinical trial eligibility. Methods: Self-identified black patients undergoing nephrectomy at a referral center from 2009-2021 were identified. Patients with end-stage renal disease were excluded. Using preoperative creatinine, height, and weight, eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation with and without race (CKD-EPI-WithRace; CKD-EPI-WithoutRace, respectively), and the Modification of Diet in Renal Disease equation with and without race (MDRD-WithRace; MDRD-WithoutRace, respectively). Distribution of patients and changes within CKD stages with different equations was considered. Theoretical exclusion at commonly observed clinical trial eGFR points was then simulated based on utilization of the race coefficient. Subgroup analysis was completed on patients with stage III-IV disease only. Results: 459 self-identified black patients that underwent nephrectomy at our institution were identified, 135 of which had stage III-IV disease. On average, eGFR decreased around 10-13ml/min/1.73m2 with removal of the race coefficient (Table). 13-22%, 6-12%, and 2-3% more black patients would fall under common clinical trial cutoffs of 60, 45, or 30ml/min cutoffs, respectively, depending on the equation used (Table). Subanalysis of stage III-IV patients only were similar. Conclusions: Race free renal function equations may inadvertently result in increased exclusion of black patients from clinical trials. [Table: see text]

Dapagliflozin in Black and White Patients With Heart Failure Across the Ejection Fraction Spectrum

BackgroundBlack people have a higher incidence and prevalence of heart failure (HF) than White people, and once HF has developed, they may have worse outcomes. There is also evidence that the response to several pharmacologic therapies may differ between Black and White patients. ObjectivesThe authors sought to examine the outcomes and response to treatment with dapagliflozin according to Black or White race in a pooled analysis of 2 trials comparing dapagliflozin to placebo in patients with heart failure with reduced ejection fraction (DAPA-HF [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure]) and heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction (DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]). MethodsBecause most self-identified Black patients were enrolled in the Americas, the comparator group was White patients randomized in the same regions. The primary outcome was the composite of worsening HF or cardiovascular death. ResultsOf the 3,526 patients randomized in the Americas, 2,626 (74.5%) identified as White and 381 (10.8%) as Black. The primary outcome occurred at a rate of 16.8 (95% CI: 13.8-20.4) in Black patients compared with 11.6 (95% CI: 10.6-12.7) per 100 person-years in White patients (adjusted HR: 1.27; 95% CI: 1.01-1.59). Compared with placebo, dapagliflozin decreased the risk of the primary endpoint to the same extent in Black (HR: 0.69; 95% CI: 0.47-1.02) and White patients (HR: 0.73 [95% CI: 0.61-0.88]; Pinteraction = 0.73). The number of patients needed to treat with dapagliflozin to prevent one event over the median follow-up was 17 in White and 12 in Black patients. The beneficial effects and favorable safety profile of dapagliflozin were consistent across the range of left ventricular ejection fractions in both Black and White patients. ConclusionsThe relative benefits of dapagliflozin were consistent in Black and White patients across the range of left ventricular ejection fraction, with greater absolute benefits in Black patients. (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure [DAPA-HF]; NCT03036124; Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213)

Omecamtiv Mecarbil in Black Patients With Heart Failure and Reduced Ejection Fraction: Insights From GALACTIC-HF

BackgroundOmecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic. ObjectivesThe purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients. MethodsIn GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patients with symptomatic HF, elevated natriuretic peptides, and left ventricular ejection fraction (LVEF) ≤35% were randomized to omecamtiv mecarbil or placebo. The primary outcome was a composite of time to first event of HF or cardiovascular death. The authors analyzed treatment effects in Black vs White patients in countries contributing at least 10 Black participants. ResultsBlack patients accounted for 6.8% (n = 562) of overall enrollment and 29% of U.S. enrollment. Most Black patients enrolled in the United States, South Africa, and Brazil (n = 535, 95%). Compared with White patients enrolled from these countries (n = 1,129), Black patients differed in demographics, comorbid conditions, received higher rates of medical therapy and lower rates of device therapies, and experienced higher overall event rates. The effect of omecamtiv mecarbil was consistent in Black vs White patients, with no difference in the primary endpoint (HR = 0.83 vs 0.88, P-interaction = 0.66), similar improvements in heart rate and N-terminal pro–B-type natriuretic peptide, and no significant safety signals. Among endpoints, the only nominally significant treatment-by-race interaction was the placebo-corrected change in blood pressure from baseline in Black vs White patients (+3.4 vs −0.7 mm Hg, P for interaction = 0.02). ConclusionsGALACTIC-HF enrolled more Black patients than other recent HF trials. Black patients treated with omecamtiv mecarbil had similar benefit and safety compared with White counterparts.

Race-free renal function estimation equations and potential impact on Black patients: Implications for cancer clinical trial enrollment.

Black patients face disparities in cancer outcomes. Additionally, Black patients are more likely to be undertreated and underrepresented in clinical trials. The recent recommendation to remove race from the estimated glomerular filtration rate (eGFR) results in lower eGFR values for Black patients. The ramifications of this decision, both intended and unintended, are still being elucidated in the medical community. Here, the authors analyze the removal of race from eGFR for Black patients with cancer, specifically with respect to clinical trial eligibility. In a cohort of self-identified Black patients who underwent nephrectomy at a tertiary referral center from 2009 to 2021 (n=459), eGFR was calculated with and without race in commonly used equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] and Modification of Diet in Renal Disease [MDRD]). The distribution of patients and changes within chronic kidney disease stages with different equations was considered. Theoretical exclusion at commonly observed clinical trial eGFR points was then simulated on the basis of the utilization of the race coefficient. The median eGFR from CKD-EPI was significantly higher with race (76ml/min/1.73 m2 ) than without race (66ml/min/1.73 m2 ; p<.0001). The median eGFR from MDRD was significantly higher with race (71.0ml/min/1.73 m2 ) than without race (58ml/min/1.73 m2 ; p<.0001). Observing results in the context of common clinical trial cutoff points, the authors found that 13%-22%, 6%-12%, and 2%-3% more Black patients would fall under common clinical trial cutoffs of 60, 45, and 30ml/min, respectively, depending on the equation used. A subanalysis of stage III-IV patients only was similar. Race-free renal function equations may inadvertently result in increased exclusion of Black patients from clinical trials. This is especially concerning because of the underrepresentation and undertreatment that Black patients already experience. Black patients experience worse oncologic outcomes and are underrepresented in clinical trials. Kidney function, as estimated by glomerular filtration rate equations, is a factor in who can and cannot be in a clinical trial. Race is a variable in some of these equations. For Black patients, removing race from these equations leads to the calculation of lower kidney function. Lower estimated kidney function may result in more black patients being excluded from clinical trials. The inclusion of all races in clinical trials is important for offering best care to everyone and for making results from clinical trials applicable to everyone.

Abstract PR002: Transcriptomic influences of racial disparities in Black patients with pancreatic neuroendocrine tumors

Abstract Introduction: There are known disparities in outcomes between Black and White patients with pancreatic neuroendocrine tumors (pNETs). Recently, Black patients have been shown to have higher rates of lymph node metastasis in smaller tumors than White patients, indicating possible differences in tumor biology. Numerous prognostic gene expression differences between racial groups have been reported in other cancers, but no such analysis has been conducted in pNETs. This study aims to evaluate pNET transcriptomes for differential expression that may be influencing racially disparate outcomes. Methods: Quality control of archival resected pNETs and demarcation of cancer cells were performed by a board-certified pathologist. Cells were laser microdissected from formalin-fixed, paraffin-embedded specimens, and RNA isolated. Sequencing was performed on an Illumina NextSeq550 at 30 million reads/sample. Alignments to the GRCh38 transcriptome annotation were performed using Salmon and differentially expressed genes (DEG’s) determined using DESeq2. Significant DEGs were determined by FDR-adjusted p-value (q-value; qv) &amp;lt; 0.05 and log2 fold-change (log2FC) ≥ ±2. Gene set enrichment analysis was performed using clusterProfiler and the Gene Ontology (GO) consortium gene sets. Ingenuity Pathway Analysis (IPA) was then conducted to determine regulator effect networks. Results: RNA sequencing was conducted on 14 and 16 grade and sex-matched primary pNETs from self-identified Black and White patients, respectively. Mean age was 51 for Black and 56 for White patients. 11/16 (69%) of White and 9/14 (64%) of Black patients were female. 8 Black patients and 8 White patients had grade 1 tumors, while 6 Black patients and 8 White patients had Grade 2 tumors. Metastatic disease was present in 4 Black and 5 White patients. Overall, 372 genes were significantly differentially expressed and 179 GO gene sets were differentially enriched between groups. Notably, among the top 10 most significantly enriched biological processes were: angiogenesis/blood vessel and vasculature development (qv=1.34e-07, normalized enrichment score [NES]=1.89), positive regulation of cell migration and locomotion (qv=1.34e-07, NES=1.91), and humoral immune response (qv= 9.8e-07, NES=-2.06). Among the top 5 regulator effect networks identified by IPA were: angiogenesis of lesion/cell movement of monocytes (consistency score [CS]=19.3), activation of blood cells (CS=18.9), and activation of cells (17.9). Conclusion: Numerous gene sets and pathways related to blood vessel development and cellular migration, representing key elements in the development of metastatic disease, are significantly enriched in pNETs from Black patients. Additionally, gene sets and pathways related to the immune response are downregulated in Black patients. These data indicate differences in tumor biology that may influence disparate outcomes reported in Black patients with pNETS. Sequencing of additional samples and incorporation of genetic ancestry are necessary to validate these findings. Citation Format: Brendon Herring, Rachael Guenter, Deepti Dhall, Herbert Chen, Clayton Yates, John Bart Rose. Transcriptomic influences of racial disparities in Black patients with pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR002.

Sociodemographic Factors Associated with Late-Stage Presentation of Adolescent Idiopathic Scoliosis

INTRODUCTION: Adolescent idiopathic scoliosis (AIS) is a common referral to pediatric orthopedic surgeons. Timely treatment with appropriate bracing decreases the risk of curve progression and need for surgical intervention. Despite pediatrician screening, patients still present to orthopaedic surgeons with curve magnitudes too significant for appropriate nonoperative bracing. METHODS: This retrospective cross-sectional study included patients 10 to 18-years-old diagnosed with AIS between 2011 and 2021 at a major metropolitan tertiary care center. Patients were excluded if initial radiographs were obtained more than one week after clinical diagnosis. Scoliosis severity was classified based on initial radiographs. Sociodemographic factors were recorded including patient address, which was cross-referenced with the diversitydatakids.org Child Opportunity Index (COI) database (which analyzes quality of resources in a geographic area). RESULTS: Sociodemographic factors, especially race, health insurance status, and lower resourced addresses, are significantly associated with late-stage presentation of scoliosis in a major metropolitan city (Fig. 1). The percentage of self-identified black patients with severe scoliosis (40%) was twice that of any other race (20%). Similarly, the percentage of patients from very low resourced areas with severe scoliosis (31%) was nearly double that of patients from very high resourced areas (16%). Nearly 25% of patients with public health insurance presented with severe scoliosis, 5% more than patients with private health insurance.CONCLUSION: Early identification of scoliosis and timely referral to pediatric orthopedic surgeons requires public health initiatives to educate primary care providers, pediatricians, and scoliosis screeners and address access to care in geographic areas with known low COI scores.

Association of B7-H3 expression with racial ancestry, immune cell density, and androgen receptor activation in prostate cancer.

BackgroundB7 homolog 3 (B7‐H3) is an immunomodulatory molecule that is highly expressed in prostate cancer (PCa) and belongs to the B7 superfamily, which includes PD‐L1. Immunotherapies (antibodies, antibody‐drug conjugates, and chimeric antigen receptor T cells) targeting B7‐H3 are currently in clinical trials; therefore, elucidating the molecular and immune microenvironment correlates of B7‐H3 expression may help to guide trial design and interpretation. The authors tested the interconnected hypotheses that B7‐H3 expression is associated with genetic racial ancestry, immune cell composition, and androgen receptor signaling in PCa.MethodsAn automated, clinical‐grade immunohistochemistry assay was developed by to digitally quantify B7‐H3 protein expression across 2 racially diverse cohorts of primary PCa (1 with previously reported transcriptomic data) and pretreatment and posttreatment PCa tissues from a trial of intensive neoadjuvant hormonal therapy.ResultsB7‐H3 protein expression was significantly lower in self‐identified Black patients and was inversely correlated with the percentage African ancestry. This association with race was independent of the significant association of B7‐H3 protein expression with ERG/ETS and PTEN status. B7‐H3 messenger RNA expression, but not B7‐H3 protein expression, was significantly correlated with regulatory (FOXP3‐positive) T‐cell density. Finally, androgen receptor activity scores were significantly correlated with B7‐H3 messenger RNA expression, and neoadjuvant intensive hormonal therapy was associated with a significant decrease in B7‐H3 protein expression.ConclusionsThe current data underscore the importance of studying racially and molecularly diverse PCa cohorts in the immunotherapy era. This study is among the first to use genetic ancestry markers to add to the emerging evidence that PCa in men of African ancestry may have a distinct biology associated with B7‐H3 expression.Lay Summary B7‐H3 is an immunomodulatory molecule that is highly expressed in prostate cancer and is under investigation in clinical trials.The authors determined that B7‐H3 protein expression is inversely correlated with an individual's proportion of African ancestry.The results demonstrate that B7‐H3 messenger RNA expression is correlated with the density of tumor T‐regulatory cells.Finally, in the first paired analysis of B7‐H3 protein expression before and after neoadjuvant intensive hormone therapy, the authors determined that hormone therapy is associated with a decrease in B7‐H3 protein levels, suggesting that androgen signaling may positively regulate B7‐H3 expression.These results may help to guide the design of future clinical trials and to develop biomarkers of response in such trials.

Putative germline findings in tumor-only and liquid biopsy sequencing in veterans with aggressive prostate cancer.

179 Background: Tumor-only and/or liquid-biopsy based Next Generation Sequencing (NGS)-based tests, which are routinely performed in metastatic prostate cancer patients, may identify putative germline mutations. The European Society of Medical Oncology (ESMO) made recommendations on findings which should be referred for germline genetic testing; however, it is unknown the burden of genetic testing referrals that may result from implementation of these recommendations. We therefore determined the frequency of putative germline findings in Veterans with metastatic prostate cancer who have undergone NGS-based sequencing of tumor and/or cell-free DNA (cfDNA) on the Foundation Medicine (FMI) platform. Methods: This is a retrospective analysis of Veterans with FMI NGS testing results reported from January 2019-February 2021 who had prostate cancer as the submitted diagnosis and metastatic diagnosis according to a VINCI natural language processing tool. Raw variant data were extracted from FMI reports and harmonized for variant annotation. Variants were annotated using ANNOVAR. Putative germline mutations were defined as 1) likely pathogenic or pathogenic (LP/P) by Clinvar annotation and VAF&gt; 30%. Mutation rates are reported in genes recommended by ESMO to trigger referral for germline testing in all tumor types and all ages of diagnosis and proposed prostate cancer susceptibility genes ( ATM, BARD1, CHEK2). Results: 1,597 Veterans with metastatic prostate cancer underwent FMI NGS testing (63% White, 33% African American, 4% other). Median age was 66 years, with 78.6% of cases from men &gt;60 years. Of 1,597 prostate cancer patients who underwent blood or tumor testing, n=85 (5.3%) had an LP/P mutation in an ESMO-guideline gene. When mutations in ATM, BARD1 and CHEK2 were added, n=133 (8.3%) of patients had an LP/P mutation. The most commonly identified putative germline findings were in BRCA2 (n=49 patients, 3.1%). 18 patients (1.1%) had mutations in other prostate cancer risk genes on the ESMO list ( BRCA1, MLH1, MSH2, MSH6, PMS2). 18 (1.1%) of patients had putative incidental germline findings, which included mutations in PALB2, BRIP1, RAD51C, RAD51D, SDHC. No putative incidental germline mutations were identified in RET, SDHA, SDHB, SDHD, TSC2, VHL. Comparing self-identified White versus self-identified Black patients, putative germline mutation rates were nearly the same in all ESMO-referral genes combined (8.2% vs 8.5%), BRCA2 (2.9% vs 3.0%), and ATM (2.4% vs 2.1%). Conclusions: While guidelines recommend that all veterans with metastatic prostate cancer undergo germline genetic testing, significant patient and system-level barriers continue to limit access to germline genetic testing for many Veterans. Tumor-only NGS testing, with a low rate of putative incidental findings, can help to prioritize which Veterans should be referred for germline genetic testing.

Cardiologists' Perspectives on BiDil and the Use of Race in Drug Prescribing.

We explored cardiologists' attitudes and prescribing patterns specific to the use of generic isosorbide dinitrate and hydralazine hydrochloride, and the fixed-dose patented drug, BiDil. Since the Food and Drug Administration approved BiDil in 2005 with an indication for self-identified black patients, disagreement about the appropriateness of race-based drugs has intensified and led to calls for providers and researchers to abandon race-based delimitations. This paper reports empirical evidence of cardiologists' views on BiDil's race-based indication and their ongoing inertia with respect to the debate about BiDil. We conducted a 2010 cross-sectional online survey of members of the Association of Black Cardiologists. Fifty-nine cardiologists responded to the survey. Most participants (62.7%) prescribed BiDil to their patients. More than 40% of respondents did not prescribe BiDil to any non-African Americans. When considering whether to prescribe BiDil, a patient's race determined by physician assessment was the third most important factor considered by participants. The majority of participants (72.7%) selected symptoms as the most important factor. Most participants (59.2%) perceived race as defining biologically distinct individuals. Respondents prescribed BiDil more often to African American patients than non-African American patients. However, they prescribed the generic components that makeup BiDil to African Americans and non-African American patients similarly. The survey provides useful findings that, when viewed within the context of ongoing debates about race-based medicine, show little progress toward appropriately utilizing BiDil to maximize health outcomes, yet, might inform the development of practical and effective guidelines concerning the use of race in medicine.

Abstract PO-100: Association of B7-H3 expression with racial ancestry, immune cell density and AR activation in prostate cancer

Abstract Background: B7-H3 (CD276, PD-L3) is an immunomodulatory molecule highly expressed in prostate cancer and belonging to the B7 superfamily that also includes PD-L1 (B7-H1). Immunotherapies (antibodies, antibody-drug conjugates, and CAR-T cells) targeting B7-H3 are currently in clinical trials; thus elucidating the clinical, molecular and tumor immune microenvironment correlates of B7-H3 expression may help to guide trial design and interpretation. Methods: We developed an automated, clinical-grade immunohistochemistry assay to digitally quantify B7-H3 protein expression across two racially diverse cohorts of primary prostate cancer (including one with previously reported transcriptomic data), a set of prostatic neuroendocrine small cell carcinoma, and pre- and post-treatment tumor tissues from a trial of intensive neoadjuvant hormonal therapy. Results: B7-H3 protein expression is significantly lower in self-identified Black patients and inversely correlates with percent African ancestry by ancestry-informative markers. This association with race is independent of the significant association of B7-H3 expression with ERG/ETS and PTEN status. CD276 mRNA level, but not B7-H3 protein expression, is significantly correlated with regulatory (FOXP3+) T-cell density. Finally, androgen receptor activity (AR-A) scores are significantly correlated with CD276 mRNA expression, and neoadjuvant intensive hormonal therapy is associated with a significant decrease in B7-H3 protein expression. Conclusion: These data underscore the importance of studying racially and molecularly diverse prostate cancer cohorts in the era of immunotherapy. Our study is among the first to use genetic ancestry markers to add to emerging evidence that prostate tumors from men of African ancestry may have a distinct immune milieu associated with B7-H3 expression. Citation Format: Adrianna A. Mendes, Jiayun Lu, Harsimar B Kaur, Siqun Zheng, Jianfeng Xu, Edward M. Schaeffer, Karen S. Sfanos, Janielle Maynard, Ashley E. Ross, Steven P. Balk, Mary-Ellen Taplin, Emmanuel S. Antonarakis, Corinne E. Joshu, Eugene Shenderov, Tamara L. Lotan. Association of B7-H3 expression with racial ancestry, immune cell density and AR activation in prostate cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-100.

Disparities in Cirrhosis Management of Black Patients: Do We Know What to Address?

Disparities in Cirrhosis Management of Black Patients: Do We Know What to Address?

Short-term aspirin and statin chemoprophylaxis did not reduce the risk of developing advanced adenomatous polyps in Black patients

BackgroundChemoprevention of colorectal neoplasia with aspirin and statins is under-investigated in Black patients. Since Black patients suffer disproportionately from colon cancer incidence and mortality compared to other populations, we investigated the utility of aspirin and statin in reducing advanced adenomatous polyp (AAP) risk in Black patients.MethodsWe carried out a retrospective cohort study of screening colonoscopies performed at a large urban academic center from 1/1/2011 through 12/31/2019. We analyzed self-identified Black patients with > 1 colonoscopy and no personal history of either inflammatory bowel disease or colon cancer syndromes. Our primary endpoint was first AAP development after index colonoscopy among Black patients taking both aspirin and a statin compared to those taking one or neither medication. We used multivariate logistic regression modeling to investigate our outcomes.ResultsWe found data on chemoprophylaxis use in 560 patients. The mean observation period between index colonoscopy and AAP identification was 4 years. AAP developed in 106/560 (19%) of our cohort. We found no difference in AAP risk among Black patients taking both chemoprevention medications compared to partial or no chemoprophylaxis (20% vs 18% respectively, p = 0.49). This finding remained after adjusting for age, body mass index, and tobacco use (odds ratio 1.04, 95% CI 0.65–1.67; p = 0.87).ConclusionsShort-term aspirin-statin chemoprevention did not reduce the risk of AAP development in our cohort of Black patients. Larger and long-term prospective investigations are needed to investigate the utility of chemoprophylaxis in this population.Trial Registration: Not applicable.

Survival Association of Angiotensin Inhibitors in Heart Failure With Reduced Ejection Fraction: Comparisons Using Self-Identified Race and Genomic Ancestry

It remains unclear whether there is a racial disparity in the response to angiotensin inhibitors in patients with heart failure with reduced ejection fraction (HFrEF) and whether the role of genomic ancestry plays a part. Therefore, we compared survival rates associated with angiotensin inhibitors in patients with HFrEF by self-identified race and proportion of West African genomic ancestry. Three datasets totaling 1153 and 1480 self-identified Black and White patients, respectively, with HFrEF were meta-analyzed (random effects model) for race-based analyses. One dataset had genomic data for ancestry analyses (416 and 369 self-identified Black and White patients, respectively). Cox proportional hazards regression, adjusted for propensity scores, assessed the association of angiotensin inhibitor exposure with all-cause mortality by self-identified race or proportion of West African genomic ancestry. In meta-analysis of self-identified race, adjusted hazard ratios (95% CI) for exposure to angiotensin inhibitors were similar in self-identified Black and White patients with HFrEF: 0.52 (0.31-0.85) P = 0.006 and 0.54 (0.42-0.71) P = 0.001, respectively. Results were similar when the proportion of West African genomic ancestry was > 80% or < 5%: 0.66 (0.34-1.25) P = 0.200 and 0.56 (0.26-1.23) P = 0.147, respectively. Among self-identified Black and White patients with HFrEF, reduction in all-cause mortality associated with exposure to angiotensin inhibitors was similar regardless of self-identified race or proportion of West African genomic ancestry.

Nitrate Use And Changes In Functional Status In Black Patients With Chronic Heart Failure With Reduced Ejection Fraction: Insights From The HF-ACTION Trial

Introduction Nitrate therapy (in combination with hydralazine) is recommended in black patients with heart failure with reduced ejection fraction (HFrEF) and NYHA class III-IV symptoms receiving optimal ACE/ARB and beta-blocker therapy to improve clinical outcomes; yet the effect of nitrates on functional status is not well characterized. Hypothesis We hypothesized that black patients taking nitrates would have greater improvements in measures of functional status over time compared with those not taking nitrates. Methods The HF-ACTION trial randomized 2,331 patients with chronic HFrEF (EF ≤35%) to usual care plus exercise training versus usual care alone. We analyzed data from self-identified black participants stratified by baseline nitrate use. Unadjusted and adjusted hierarchical linear regression models were used to determine the association of nitrate use with changes in functional status (6-minute walk distance [6MWD], and peak VO2) from baseline to 3 months and to explore an interaction with exercise training. Results Among 749 black patients, 198 (26%) were on nitrates at baseline. Patients taking nitrates were older, with worse NYHA class symptoms, more ischemic disease and diabetes and worse renal function than those not on nitrates. Baseline 6MWD and peak VO2 were worse among patients on nitrates than those not on nitrates (median 308 vs. 361 m and 12.4 vs. 13.4 mL/kg/min, respectively). After adjustment, there was no significant association between nitrate use and change in 6MWD or peak VO2 (Table). These results were consistent irrespective of randomization to exercise training or usual care (interaction p-values>0.05). Conclusions In this clinical trial population of self-identified black patients with chronic HFrEF, approximately one-fourth of patients were receiving nitrates at baseline and these patients tended to have worse baseline functional status. After adjustment, nitrate use was not associated with greater improvements in functional status from baseline to 3 months, and findings were consistent irrespective of concurrent exercise training. Further efforts are needed to determine optimal approaches for improving exercise capacity in black patients with HFrEF.

1376-P: Glucose-Independent Racial Disparity in HbA1c Is Present at Onset of Type 1 Diabetes (T1D)

Introduction: HbA1c is an important guide for management, diagnosis and prediction of complications in diabetes. We have shown that young black patients with established T1D have higher HbA1c than white patients even after adjustment for mean blood glucose, RBC indices, age, and gender. We hypothesized that glucose-independent racial disparity in HbA1c is also present at diagnosis of T1D. Methods: Data was collected by chart review for self-identified white and black patients who presented between Jan 2012 and Nov 2018 to the Hospital ER with untreated new onset T1D. Analyte data is from initial blood sample. Data was collected for date of birth, sex, self-identified race, weight, height, glucose, HbA1c, pH, bicarbonate, insulin, C-peptide, pancreatic autoantibodies, RBC indices. Simple correlation and comparison of means between groups was performed. This followed by multiple variable regression modeling to test the statistical effect of race, gender, age, glucose, RDW-CV and other variables on HbA1c. Results. We included 191 children with newly diagnosed T1D (69 blacks and 122 whites; 116 M, 75 F). HbA1c was correlated with glucose, insulin, c-peptide, age, RDW-CV, Hb, HCO3. blacks had higher HbA1c 11.9 ±1.9 vs. whites 11.04±2 (P=0.004), higher glucoses 530.6±230.4 vs. 441.9±211.3 mg/dL (P=0.0075), lower C-peptides 0.57± 0.42 vs. 0.76±0.61 ng/mL (P=0.019) and lower pH 7.28±0.15 vs. 7.33±0.12, (P=0.02). There was no statistical difference in age, BMI-z, HCO3 or insulin between the groups. After adjusting for age, sex, glucose, C-peptide and RDW-CV, HbA1c is still higher in blacks, P=0.037. Age, gender, glucose, C-peptide and RDW-CV were also significant covariates in the model. Conclusions. 1- HbA1c at presentation is influenced by Race, glucose, age, sex, RDW-CV, and c-peptide 2- Even after adjustment for glucose blacks have higher HbA1c than whites 3- Glucose-independent HbA1c racial difference should be taken into account for purposes of diagnosis and management of T1D. Disclosure A. Alaqeel: None. S. Chalew: None.