Universal genetic testing versus guideline-directed testing for hereditary cancer syndromes among traditionally underrepresented patients in a community oncology program.

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10588 Background: Detection of pathogenic germline variants (PGVs) has implications for cancer screening, prognostication, treatment selection, clinical trial enrollment and family testing. Published guidelines provide indications for PGV testing, determined by clinical and demographic factors, but these leave a significant number of cases missed by guideline-directed testing (incremental PGV). We have previously shown that 50% of patients with PVGs would not have been detected with guideline-based testing alone. In this project, we aimed to determine the feasibility and generalizability of this approach within a more racially/ethnically diverse cohort from a community cancer practice. Methods: We completed a prospective study of proactive germline genetic sequencing among patients with solid tumor malignancies at a community-based oncology practice in downtown Jacksonville, FL between June 2020, and September 2021. The patients were unselected for cancer type, stage, family history, race/ethnicity, and age. PGVs identified using an 84-gene NGS platform were stratified by penetrance. National Comprehensive Cancer Networks (NCCN) guidelines were used to determine incremental PGV rates. Results: 221 patients were enrolled, median age 63.0 years, 21.7% male. 56.6% of patients were white (non-Hispanic), 32.6% were black/African American, 5.4% were Hispanic. 39.8% of patients were commercially insured, 52.4% insured by Medicare/Medicaid and 2.7% uninsured. The cohort was comprised predominantly of breast cancer (61.5%), lung cancer (10.4%) and colon cancer (7.2%) patients. A total of 27 PGVs were identified in 23 patients. We found no significant difference in the rate of PGVs based on race/ethnicity. The overall rate of variants of uncertain significance (VUS) was numerically higher in black/African American patients (61.1%) compared with other ancestry (45%). 13 of 23 (56.5%) patients with detected PGVs did not meet NCCN guidelines for germline genetic screening (incremental PGVs). Conclusions: This prospective study found that universal multi-gene panel testing among patients from a racially/ethnically diverse cohort from a community cancer practice was associated with an increased detection of heritable variants with treatment implications over the predicted yield of targeted testing based on guidelines. This study is the first to evaluate this approach in an exclusively community-based practice. Clinical trial information: NCT04456140.

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