tbuckley/cabot-search huggingface dataset:
A systematic review of racial disparity in pivotal poly (ADP-ribose) polymerase (PARP) inhibitor trials.
Authors: Elizabeth John, Simranjit Sekhon, Arindam Bagchi
Journal: Journal of Clinical Oncology (2024)

e13737 Background: Breast cancer is the most common cancer diagnosed worldwide. Breast cancer related mortality has decreased in the US, however this did not extend equally to African American women (AAW). According to CDC mortality rate from breast cancer in AAW is 20% higher than other ethnic groups. Younger age at diagnosis in AAW, higher incidence of triple negative breast cancer (TNBC), and higher incidence of AA males with breast cancer suggest genetic predisposition plays an important role in the disparate outcomes based on race. In an unbiased analysis of TNBC cases, the prevalence of pathogenic germline BRCA 1 &amp; 2 mutations are twice as high as in breast cancer overall. Poly (ADP-ribose) polymerase (PARP) inhibitors have proven to be effective in germline BRCA 1 and BRCA 2 mutation associated breast cancer. However, data regarding the enrollment of racial and ethnic minorities in these pivotal trials that lead to the approval of these drugs is limited. Methods: We examined the demographic data reporting in Phase II/ III clinical trials of PARP inhibitors in breast cancer from 2016 to 2023. In order to highlight the disparities in the enrollment of minority groups we calculated an enrollment percentage of various racial groups in these trials. We conducted a systematic review of Phase II/III clinical trials of PARP inhibitors in BRCA 1 &amp; 2 mutated breast cancer reported studies with sources from PubMed, Embase, Scopus, Clinicaltrials.gov, CENTRAL and Cochrane. 56 full text studies were identified, out of which 14 met inclusion criteria. The total number of patients included was N=5,067. Five trials did not include racial data. Results: Among trials that reported race and ethnicity (N=4004), the enrollment percentage was lowest for racial and ethnic minorities. AA: 3.4%, N=136. Non- Hispanic Whites were the most common to be enrolled: 71.05%, N=2845, Asians were 16.53% N= 662, Hispanics 2.03 %; N=83 and other 6.17%, N=247. Conclusions: Racial minorities are consistently underrepresented in all the pivotal PARP inhibitor trials and contributing to the race-based disparities in breast cancer. [Table: see text]
Racial/ethnic distribution of participants in NRG oncology clinical trials: 2014-2023.
Authors: James J. Dignam, Paul A Romitti, Sue S. Yom, Felix Y Feng, Jeffrey D. Bradley, Minesh P. Mehta, Deborah Watkins Bruner, Jennifer Wenzel, Eleftherios P. Mamounas, Thomas J. George, Theodore S. Hong, Carol Aghajanian, Maria Werner-Wasik, Alexandra Thomas
Journal: Journal of Clinical Oncology (2024)

e13706 Background: External validity and applicability of clinical research relies upon characteristics of trial participants matching those of the respective disease groups in the general population. Understanding the racial/ethnic distribution of patients enrolled in recent US-based, federally sponsored Phase II and III clinical trials could inform strategies to further align characteristics of trial participants with those of disease group populations. As such, we report the racial/ethnic distribution of participants in NRG Oncology studies during 2014-2023 and compare the distribution to that from the Surveillance, Epidemiology, and End Results (SEER) program data during 2014-2020 (most recent data available). Methods: Proportions of self-reported race/ethnicity were summarized for the 33,370 trial participants enrolled since Mar 1, 2014 (NRG Oncology inception) to therapeutic, symptoms management, and other interventional trials. SEER proportions were used to benchmark NRG trials for representativeness of disease burden in the population. Results: Among NRG trial participants, 71.5% were non-Hispanic (NH) White, 9.7% NH Black, 4.9% Hispanic, and 7.8% N-H Asian (Table). Examining distributions within selected cancer sites relative to cancer proportional incidence in 2014-2020 SEER data, NRG accrual to prostate, lung, cervix, and breast cancer trials is commensurate with observed disease burden for NH Blacks and modestly lower for Asians. For other sites shown, representation was 2 to 5 percentage points lower than SEER frequencies for Blacks and Asians. For all sites, accrual of individuals of Hispanic background was lower than that reported in SEER. As the NRG trials do not reflect sampling across stages and other features of a given cancer in the population, further analysis to be presented will consist of more detailed breakdowns of trial participant disease-specific cancer stage and tumor subtype and comparison to relevant observations from the 2014-2020 SEER database. Conclusions: This high-level comparison of the racial/ethnic distribution of NRG trial participants provides supportive information for population representative enrollment in several cancer sites, but also identifies opportunities to improve enrollment diversity to represent more closely the respective affected population. Areas of success identified merit further investigation to understand if there are best practices which may be applied more broadly towards expanding access to federally funded clinical trials. [Table: see text]
Overcoming racial and ethnic disparities in clinical trial enrollment real world evidence from an NCI-Designated Cancer Center in a minority majority county.
Authors: Frank Lee, Jennifer Brooke Valerin, Farshid Dayyani
Journal: Journal of Clinical Oncology (2024)

e13708 Background: Significant racial and ethnic disparities continue to persist in clinical trial enrollment. Specifically, Asian and Hispanic individuals are severely underrepresented compared to their census estimates and make up as little as 1% and 6% respectively of all clinical trial enrollments [PMID: 35875251]. This limits the generalizability of clinical trials and consequently the application of novel therapeutics for diverse populations. This observational study looks at enrollment demographics at the University of California, Irvine (UCI) with an emphasis on minority participation in clinical trials. We hypothesized that minorities would be underrepresented in our enrollment population. Methods: The UCI Chao Family Comprehensive Cancer Center (CFCCC) is located in Orange County (OC), CA, a minority-majority county. Enrollment data from clinical trials was collected from 2015-2023 through the CFCCC clinical research database. Demographics were compared to data provided by the NIH SEER reports in both OC and United States. Results: Between 2015-2023, 2315 individuals across 3 UCI Health facilities were enrolled. Demographics were as follows: White, Asian, Black, American Indian/Alaska Native, mixed/unknown race (66.4%/20.1%/2.4%/0.7%/0.7%/ 9.3%). Non-Hispanic vs Hispanic ethnicity (77.8%/20.6%). Female vs Male sex (47.6%/52.3%). Age &lt;70 vs &gt;70 years (78.6%/21.4%). Low Income/Health Professional Shortage Areas (HPSA) vs non-Low Income/HPSA (44.9%/55.0%). Study Phase: Phase I/II (39.2%), Phase II (28.0%), Phase III (29.3%), Phase II/III (3.0%), and Phase IV (0.3%). Study sponsor: Industry (61.2%), Investigator initiated (23.5), Cooperative group (14.9%), other (0.3%). Most notably, the Asian enrollment (20.1%) and Hispanic enrollment (20.6%) exceeded demographic representation of Asians (15.6%) and Hispanics (17.3%) in OC. Conclusions: Our results demonstrate that accrual of minorities is feasible across all types of clinical trials. These findings suggest that minorities are not inherently less likely to enroll in clinical trials. A clinical trial portfolio mirroring the catchment area might improve accrual of minorities. Enrollment based on race/ethnicity and trial phase/sponsor will be presented at the meeting.
Trends of demographic and clinical traits of young patients with breast cancer from the National Cancer Database: Disproportionate effect on underrepresented underserved populations.
Authors: Cynthia Mark, Vivek Pujara, Marissa K. Boyle, Yuan Yuan, Jin Sun Bitar
Journal: Journal of Clinical Oncology (2024)

e13715 Background: Over the past decade, there has been increasing incidence of young patients diagnosed with cancer. Despite these developments, there is still uncertainty surrounding the factors and patterns contributing to the rising incidence in young age. This study aims to explore the demographic and clinical characteristics of young breast cancer (YBC) patients. Methods: We obtained characteristics and survival data from 206,156 of young patients (≤ 40 years of age) diagnosed with breast cancer between 2005 and 2019 in the National Cancer Database (NCDB). The demographic and clinical data were subdivided the patients into two comparison groups based on year of diagnosis with 10 years interval (2005-2009, Old vs. 2015-2019, New group). The z-score test was employed to measure the changes in the 2 groups. Cox proportional hazards model was used to explore the variables influencing overall survival (OS). Results: Overall, the absolute number of YBC patients have been increasing every year. The comparison between Old (55397 pt) and New groups (67930 pt) showed increase in Hispanic (4,575 (8.3%) vs 6,720 (9.9%), p &lt;0.0001), Black (8,695 (15.7%) vs 11,156 (16.4%), p=0.0005), Asian (2,592 (4.7%) vs 4,512 (6.6%), p&lt;0.0001), and other minority populations. Non-Hispanic White showed no change (p=0.1902). Additionally, there was a reduction in the proportion of patients with private insurance (43,940 (79.3%) vs 51,104 (75.2%), p&lt;0.0001) and an increase in patients with Medicaid (5,893 (10.6%) vs 10,694 (15.7%), p&lt;0.0001). Interestingly, there was a significant increase in hormone positive disease (35,142 (63.4%) vs 49,409 (72.7%), p&lt;0.0001), while no change in hormone negative disease. In New group, the influence of race is evident in the observed variations in OS (Table). Finally, patients with Medicaid or without insurance exhibited a diminished OS compared to those with private insurance, and a lower median income was associated with a negative impact on OS. Conclusions: For YBC patients, the proportion of underrepresented and underserved population is increasing. There is an increasing rate of hormone positive disease. This can cause substantial personal and societal implications, such as family planning and early menopause. Therefore, awareness of these at-risk populations is important for early identification of breast cancer and mitigation of poorer outcomes. [Table: see text]
Association of immune checkpoint inhibitor introduction and changes in survival disparities by health insurance coverage among individuals newly diagnosed with advanced cancers in the US.
Authors: Jingxuan Zhao, Ilana Graetz, David Howard, Robin Yabroff, Joseph Lipscomb
Journal: Journal of Clinical Oncology (2024)

1580 Background: First approved by the US Food and Drug Administration (FDA) in 2011, immune checkpoint inhibitors (ICIs) have transformed treatment options for many cancers. Unfortunately, due to their high cost, individuals without health insurance coverage may not be able to afford them. Therefore, the introduction of ICIs may lead to greater disparities in cancer survival between patients with and without health insurance. This study examined the association of health insurance with changes in survival disparities associated with the introduction of ICIs. Methods: We identified individuals newly diagnosed at age 18-64 years at stage IV with any one of the following cancers with FDA approval for ICI treatment, including melanoma (first approved 03/25/2011, n=9992); HR+ HER- female breast cancer (02/03/2015, n=13632); non-small cell lung cancer (NSCLC; 03/04/2015, n=113866); and renal cell carcinoma (RCC; 11/23/2015, n=15403) from the National Cancer Database. Individuals with private health insurance or who were uninsured at the time of the cancer diagnosis were included. For each cancer, we applied a difference-in-differences (DD) approach to examine the changes in two-year overall survival before and after the ICI FDA approval date among individuals without health insurance compared to those with private health insurance, using flexible parametric survival models and controlling for key sociodemographic factors. Results: As shown (Table), among patients diagnosed with melanoma, 2-year survival rate increased from 16.33% pre-ICI approval to 27.04% after ICI approval among patients who were uninsured and increased from 28.22% to 45.45% among patients with private health insurance, with the disparity by health insurance status widened by 4.58 (95% confidence interval [CI] = 0.02 to 9.14) percentage points (ppt) after adjusting for sociodemographic factors. For patients diagnosed with stage IV NSCLC, the disparity by health insurance widened by 1.58 (95% CI = 0.52 to 2.64) ppt. Conclusions: The introduction of ICIs increased disparities in survival by health insurance status. Policies to improve health insurance coverage options or make new treatments more affordable to uninsured patients are needed. [Table: see text]
Automated digital oncologic data review for breast cancer research: AI-enabled mCODE and field-of-interest extraction framework.
Authors: JI-Woo Choi, Seho Park, Joohyuk Sohn, Dae Hyun Lew, Sihyun Sung, Ye-Lim Choi, Sarang Lee, Eun-Jung Yang
Journal: Journal of Clinical Oncology (2024)

e12647 Background: Enhancing outcomes in cancer care and research can be optimally achieved by accelerating data extraction from unstructured electronic health resources. Understanding the association between treatment response markers and long-term outcomes is crucial for refining cancer therapeutic approaches and improving patient prognosis. In this study, we explore the association of oncologic outcomes with pathologic complete response (pCR) in high-risk early-stage breast cancer treated with neoadjuvant chemotherapy (NACT) using automated oncologic data extraction framework. Methods: Patients with primary stage I-III breast cancer who received NACT followed by mastectomy, with or without immediate breast reconstruction from January 2010 to August 2023 were retrospectively analyzed. We extracted pCR results and data on clinical and pathological stage, tumor subtype, grade, and treatment regimens and factors affecting postoperative complications from electronic medical records based on the AI enabled-mCODE (Minimal Common Oncology Data Elements) and fields of interest extraction framework. Employing mixed-effects Cox models, we explored the association between pCR and event-free survival (EFS), distant recurrence free Survival (DRFS) and overall survival (OS). Survival curves of patients were estimated using Kaplan-Meier method. Multivariate analysis was performed to evaluate the predictive factors for pCR. Results: Overall, 2725 patients were analyzed. The median age was 50.6 years. The median follow-up was 67 months. pCR was achieved in 31.0%. Hazard ratio for pCR vs. non-pCR were 0.34 for EFS (95% CI, 0.25-0.45), 0.32 for DRFS (95% CI, 0.23-0.43), 0.21 for OS (95% CI, 0.13-0.34), varying from 0.13 to 0.56 for EFS, 0.12 to 0.48 for DRFS and 0.07 to 0.40 for OS. The presence of pCR remained prognostic for event-free survival in multivariate models adjusted for age, tumor size, and nodal status at baseline. Conclusions: This study confirms that patients achieving pCR after NACT have better long-term survival outcomes that patients who do not. Oncologic data extraction from unstructured electronic medical records using AI-enabled extraction framework can be expected to enhance robust cancer research and generate valuable insights from real-world practice settings for tailored therapeutic decision-making. [Table: see text]
Pre-event ‘medical time out’
Authors: Ron Courson, Glenn Henry, Kyle Borque, Douglas J Casa, Micki S Collins, Christianne Eason, Greg Elkins, Jim Ellis, Warne Fitch, Richard Hunt, James Kyle, Lawrence J Lemak, Bert Mandelbaum, Kevin Morley, Catherine S O'Neal, Robb S Rehberg, Fred Reifsteck, Samantha E Scarneo-Miller, Allen Sills
Journal: British Journal of Sports Medicine (2024)
First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with <i>PIK3CA</i>-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses.
Authors: Dejan Juric, Kevin Kalinsky, Nicholas C. Turner, Komal L. Jhaveri, Peter Schmid, Sherene Loi, Cristina Saura, Seock-Ah Im, Patrapim Sunpaweravong, Huiping Li, Antonino Musolino, Qingyuan Zhang, Zbigniew Nowecki, Roland Ching-Yu Leung, Eirini Thanopoulou, Noopur Shankar, Guiyuan Lei, Jacob Devine, Thomas J Stout, Sibylle Loibl
Journal: Journal of Clinical Oncology (2024)

1003 Background: INAVO120 (NCT04191499) showed significantly and meaningfully improved investigator-assessed progression-free survival (PFS; stratified hazard ratio 0.43) with Inavo+Palbo+Fulv v Pbo+Palbo+Fulv, and manageable safety and tolerability. To further characterize the substantial benefit/risk of the Inavo triplet, we assessed additional clinically relevant efficacy endpoints, detailed safety data of key adverse events (AEs) for Inavo (hyperglycemia [HG], diarrhea, rash, stomatitis), and pt-reported outcomes (PROs). Methods: Efficacy endpoints includedtime from randomization to end of next-line treatment (tx; proxy for PFS2) and to first chemotherapy (TTFC). Key AEs were reported by grouped terms. PROs were assessed by PRO-CTCAE, an overall bother item, BPI-SF, and EORTC QLQ-C30. Results: Increases in median “PFS2” (24.0 v 15.1 mo; unstratified hazard ratio: 0.59 [95% CI, 0.42–0.83]) and TTFC (NE v 15.0 mo; unstratified hazard ratio: 0.53 [95% CI, 0.37–0.78]) were observed in the Inavo v Pbo arm (median follow-up: 21.3 mo; Table). Key AEs were mostly G1–2 and had resolved (Table). No key AEs were G4–5. In the Inavo arm, among pts who experienced key AEs (HG, diarrhea, rash, stomatitis), median time to first onset was 7, 15, 29, and 13 days, respectively. The key AEs were managed with standard supportive care and Inavo dose interruptions/reductions. One pt discontinued Inavo due to HG; one, due to stomatitis. Pts receiving Inavo experienced a longer duration of time without worsening pain severity and maintained their day-to-day functioning and health-related quality of life on tx. Most pts in both arms reported levels of selected symptomatic AEs from the PRO-CTCAE and overall tx bother as moderate or less, indicating that Inavo does not contribute additional tx burden. Conclusions: Inavo+Palbo+Fulv was associated with sustained benefit beyond disease progression, delaying chemotherapy administration, with manageable safety and tolerability that was reflected in PROs; hence, supporting it as a new standard of care. Clinical trial information: NCT04191499 . [Table: see text]
Lipolysis-Stimulated Lipoprotein Receptor in Proximal Tubule, BMP-SMAD Signaling, and Kidney Disease
Authors: Min Jiang, Xiangdong Wang, Zhenni Chen, Xin Wang, Yanan An, Lixia Ding, Mengyuan Xu, Baozhen Fan, Peng Jiao, Chao Wang, Mingxia Wang, Hui Sun, Shengtian Zhao, Yongfeng Gong
Journal: Journal of the American Society of Nephrology (2024)

Key Points We identify that lipolysis-stimulated lipoprotein receptor is highly enriched in the nucleus of mouse and human kidney. This study provides new insights into the role of lipolysis-stimulated lipoprotein receptor in kidney disease. Background Lipolysis-stimulated lipoprotein receptor (LSR) is a single-pass membrane protein that plays essential roles in tricellular tight junction organization in the epithelium and endothelium, but its function in kidney physiology and disease development remains unknown. Methods Conditional Lsr deletion mice were generated and analyzed to investigate the function of LSR in proximal tubule. Unilateral ischemia-reperfusion was used as an injury model to investigate the role of LSR in AKI and the progression to CKD. Detailed mechanistic analyses were conducted using whole-transcriptome RNA sequencing, immunofluorescence, dual-luciferase reporter gene assay, coimmunoprecipitation, RNA immunoprecipitation, and adeno-associated virus-mediated gene overexpression and knockdown. Results The nuclear localization of LSR was found in the kidney. Proximal tubule–specific Lsr knockout mice exhibited alleviated kidney damage and fibrosis compared with those in wild-type mice in response unilateral ischemia-reperfusion injury. Loss of LSR resulted in downregulation of Chrdl1 and activation of bone morphogenetic protein (BMP)-mothers against decapentaplegic homolog (SMAD) signaling in proximal tubules. Treatment with CHRDL1 counteracted the protective effect of LSR deletion in the unilaterally ischemic injured kidney. In addition, the systemic delivery of Chrdl1 short hairpin RNA attenuated injury-induced kidney fibrosis. LSR formed a complex with 14-3-3θ in the nucleus of proximal tubular cells, thereby reducing the interaction between human antigen R and 14-3-3θ, consequently leading to the translocation of unbound human antigen R to the cytoplasm. The absence of LSR promoted the association of 14-3-3θ with human antigen R, potentially resulting in decreased human antigen R levels in the cytoplasm. Reduced human antigen R levels impaired Chrdl1 mRNA stability, subsequently leading to the activation of BMP-SMAD signaling. Conclusions Deletion of LSR in proximal tubule deregulated Chrdl1 to activate BMP-SMAD signaling and ameliorated kidney disease.
Proton Pump Inhibitors and CKD
Authors: Morgan E. Grams, F. Perry Wilson
Journal: Journal of the American Society of Nephrology (2024)

1Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, New York 2Department of Population Health, New York University Grossman School of Medicine, New York, New York 3Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 4Clinical and Translational Research Accelerator, Yale University, New Haven, Connecticut 5Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut Correspondence: Dr. Morgan E. Grams, email: [email protected] See related article, "The Effects of Pantoprazole on Kidney Outcomes: Post Hoc Observational Analysis from the COMPASS Trial," on pages XXX–XXX.
Evolution of Biologically Related Living Kidney Donation in the United States from 1988 to 2022
Authors: Fawaz Al Ammary, Simeon Adeyemo, Krista L. Lentine, Abimereki D. Muzaale
Journal: Journal of the American Society of Nephrology (2024)

Al Ammary, Fawaz; Adeyemo, Simeon; Lentine, Krista L.; Muzaale, Abimereki D. Author Information
Legislative and Regulatory Changes Affecting the US Transplant System
Authors: Sumit Mohan, Syed Ali Husain
Journal: Journal of the American Society of Nephrology (2024)

1Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, NY 2Columbia University Renal Epidemiology Group, New York, NY 3Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY aCorresponding Author: Sumit Mohan, MD, MPH, Professor of Medicine & Epidemiology, Division of Nephrology, Department of Medicine, Columbia University Medical Center, 622 W 168th St, PH4-124, New York, NY 10032, [email protected]