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Abstract
INTRODUCTION The advent of deep molecular analysis using next generation sequencing (NGS) leads to a better understanding of carcinogenesis and the ability to identify and target specific mutations. METHOD After obtaining IRB approval, patients were approached in several oncology clinics in Grady Health System and explained the risk and benefit of being tested for molecular testing to better guide clinical management of their disease. After informed consent, we carried out Clinical Laboratory Improvement Amendments of 1988 (CLIA) NGS for a large number of targetable genes, tumor mutation burden (TMB), microsatellite instability (MSI), and the somatic transcriptome. We identified germline mutations, actionable genes, biologically significant genes, pertinent negative, variants of unknown significance, tumor profile-matched clinical trials and the recommended therapies based on CLIA NGS findings. All data and medical reports were made available to treating physicians. RESULTS We tested 280 patients, of which 206 were women and 74 men. 95% are represented by African American population. The majority of our patients had endometrial cancer (33%), breast cancer (21%), lung (9%), colon (8&), ovary (7.5%), prostate (3.5%) and head and neck (3.5%). Fewer carcinomas were of thyroid, other gastrointestinal and genitourinary origin. Of the most frequent cancers in our pilot study, endometrial carcinomas, 26% displayed significant tumor burden with 53% demonstrating > 50 mutations. In additional, endometrial cancers were found to be MSI stable in 84% of cases, 11% had a germline mutation, 63% had actionable mutations (range of 1-9), 68% with biologically relevant mutations (range 2-5) and 100% had VUS (range 1 to 21). Importantly, 18% of the cases studied had novel treatment indications. Of the breast carcinomas, 44% of cases displayed a significant tumor burden with 29% demonstrating > 50 mutations. In additional, 76% of breast cancer case were found to be MSI stable in, 10% had a germline mutations, 71% had actionable mutations, 90% with biologically relevant mutations (range 1-7), and 86% had VUS (range 1 to 14). Clinical trials were available in 66% and 76% cases had unique treatment indications. Of the lung carcinomas, 89% had tumor mutation burden with > 50 mutations. 100% had VUS (range 2-15) and 44% had treatment indication. CONCLUSION Providing access to CLIA NGS to safety net hospital cancer patients revealed unique somatic changes and treatment options. Taken together, this approach is an important step to democratize precision medicine and improve health outcomes to advance health equity.
Citation Format: Gabriella M. Oprea-Ilies, LaTrisha L. Horne, Eddie R. Stanley, Regina Lee, Joel Okoli, Giuseppe Del Priore, Pooja Mishra, Roland Matthew, Eric L. Flenaugh, Brian Rivers, James W. Lillard, Sam Sirotnikov, Mallik Matthews. Landscape of the molecular changes in the most frequent tumors in a safety net hospital [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A056.