Original Abstract
RATIONALE: Genetic testing is standard of care in Non-small Cell Lung Cancer(NSCLC). Few studies evaluate concurrent Endobronchial Ultrasound-Transbronchial Needle Aspiration(EBUS-TBNA) and liquid biopsy for Next Generation Sequencing(NGS). OBJECTIVES: Compare diagnostic yield differences for detecting clinically relevant mutations via NGS in concurrent EBUS-TBNA and liquid biopsies. METHODS: Prospective observational cohort study of NSCLC patients undergoing concurrent biopsies. MEASUREMENTS: Yield differences, receiver operating characteristic (ROC) and kappa statistics were calculated for clinically relevant mutations. MAIN RESULTS: Of 199 subjects, diagnostic yield for EGFR was 9.5% in EBUS-TBNA and 7.0% in blood with yield difference 2.5%(95% CI: 3.4%, 8.5%, p = 0.36). For clinically relevant targets, there were 79(39.7%) from EBUS-TBNA and 49(29.6%) from blood with yield difference 15.1%(95% CI: 5.5%, 24.2%, p = 0.001). ROC statistics for detection of clinically relevant mutations (where tissue results were the gold standard) included: sensitivity 0.53 (95% CI: 0.42, 0.64), specificity: 0.95(95% CI: 0.90,0.98), positive predictive value: 0.89 (95% CI: 0.77, 0.96), negative predictive value: 0.74 (95% CI: 0.65, 0.81), and kappa statistic: 0.51 (95% CI: 0.39, 0.63). There were 37 (18.6%) participants with mutations in tissue only and 7(3.5%) with mutations in blood only, while 42(21.1%) had mutations reported from both sources. CONCLUSIONS: EBUS-TBNA was more likely to detect mutations than blood. However, some patients had mutations in blood only, suggesting blood testing is complementary. Strategies are needed to improve NGS turnaround time(TAT) and QNS definition.