9005 Background: Cancer racial disparities may exist at many levels in the health care system, from screening to timely diagnosis and treatments received, as well as clinical trial enrollment. This study investigated differences in black versus white race among patients with NSCLC undergoing biomarker testing and clinical trial enrollment in the US. Methods: This retrospective observational study utilized the Flatiron Health database, which includes longitudinal data of patients with advanced/metastatic NSCLC. Patients were eligible if they had evidence of systemic therapy in the database from 1/1/2017 through 10/30/2020. Descriptive analyses summarized differences by race in biomarker testing and trial enrollment. Multivariable regression examined the relationship between these factors. Results: A total of 14,768 patients were eligible: 9,793 (66.3%) were white and 1,288 (8.7%) were black. 76.4% of white patients and 73.6% of black patients underwent at least one single molecular test or comprehensive genomic analysis (p = 0.03). Next-generation sequencing (NGS) was performed among 50.1% of white patients and 39.8% of black patients (p < 0.0001. Trial participation was observed among 3.9% of white and 1.9% of black patients (p = 0.0002). There was a statistically significant association between race (white vs black) and both biomarker testing (ever vs never) and trial participation (yes vs no) (both p < 0.001, unadjusted chi square). Differences in NGS testing, baseline biomarker testing, and race were retained as statistically significant (p < 0.01) in adjusted regression analyses. The receipt of first-line targeted therapy was comparable between white and black patients (10.2% and 9.2%, respectively, p = 0.24); however, this summary did not consider biomarker test results. First line use of pembrolizumab+carboplatin+pemetrexed was observed among 19.8% of white and 22.6% of black patients; carboplatin+paclitaxel was observed among 16.5% and 18.6%, and single-agent pembrolizumab was observed among 14.8% and 11.5%, respectively. Conclusions: The use of NGS-based testing, which is recommended by the National Comprehensive Cancer Network Clinical Guidelines in Oncology for patients with advanced/metastatic NSCLC, is the most notable disparity among black patients, with more than a 10 percentage-point difference in receipt of this testing versus white counterparts. This may in part contribute to the more than double the rate of participation in clinical trials observed among white patients, as many second line and beyond trials utilize molecular targets as inclusion criteria. While multiple factors are known to impact health care disparities, access to and receipt of appropriate biomarker testing may be an attenable goal in order to ensure equal access to quality care.
Loss of plasma membrane integrity (LPMI) is a hallmark of necrotic cell death. The involvement of complement and ROS in the development of LPMI during the early stages of murine myocardial ischemia-reperfusion injury was investigated. LPMI developed within 1 hour of reperfusion to a level that was sustained through 24 hours. C3 deposition became significant at 3 hours’ reperfusion and thus contributed little to LPMI prior to this time. SOD1 transgenic mice had significantly less LPMI compared with WT mice at 1 hour of reperfusion but not at later time points. Catalase transgenic mice were not protected from LPMI at 1 hour’s reperfusion compared with WT mice, but had 69% less LPMI at 3 hours’ reperfusion. This protection was transient. At 24 hours’ reperfusion the LPMI of catalase transgenic mice was identical to that of WT mice. The delayed benefits of over-expressed catalase compared with SOD1 are consistent with its antioxidant action downstream of SOD1. The onset of LPMI occurs within 1 hour of reperfusion and is maintained through 24 hours. ROS contribute significantly to LPMI during the first 3 hours of reperfusion, while complement deposition, which becomes significant after 3 hours’ reperfusion, may contribute thereafter.
PURPOSE Comprehensive tumor biomarker testing is a fundamental step in the selection of highly effective molecularly driven therapies for a variety of solid tumors. The primary objective of this study was to examine racial differences in biomarker testing and clinical trial participation in the United States using a real-world database. METHODS Patients in a real-world deidentified database diagnosed with advanced/metastatic non–small-cell lung cancer (NSCLC), metastatic colorectal cancer (CRC), or metastatic breast cancer were eligible. Biomarker testing and clinical trial participation was compared between Black and White racial groups using chi-squared test and stepwise logistic regression controlling for baseline covariates. RESULTS A total of 23,488 patients met eligibility criteria. Next-generation sequencing (NGS) testing rates differed significantly between White versus Black race before first-line therapy (36.6% v 29.7%, P < .0001) and at any given time (54.7% v 43.8%, P < .0001) in the nonsquamous NSCLC cohort. Similar disparities in NGS testing rates at any time during the study were observed among patients with CRC (White 51.6%; Black 41.8%, P < .0001). No differences were observed in the breast cancer cohort. Patients of Black race were less likely to be treated in a clinical trial in the overall NSCLC cohort when compared with White counterparts (3.9% v 2.1%, P = .0002). A statistically significant relationship between biomarker/NGS testing and clinical trial enrollment was observed in all cohorts ( P < .003) after adjusting for covariates. CONCLUSION In a real-world database, significant disparities in NGS-based testing rates were observed between Black and White races in NSCLC and CRC. NGS and any biomarker testing were both associated with trial enrollment in all cohorts. There is a need for interventions to promote access to comprehensive testing for patients with advanced/metastatic tumors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.