Concurrent tissue and liquid NGS improves NSCLC mutation detection, with blood capturing tissue-negative cases
Investigators evaluated concurrent endobronchial ultrasound-guided transbronchial needle aspiration and blood-based liquid biopsies for next-generation sequencing in 199 patients with non-small cell lung cancer. Tissue sampling demonstrated a higher overall diagnostic yield for clinically relevant mutations compared to plasma (39.7% versus 29.6%), though liquid biopsies identified mutations in 3.5% of cases missed by tissue. The study reports that plasma testing achieved a sensitivity of 0.53 and specificity of 0.95 against tissue as the reference standard. These findings indicate that while tissue remains the preferred specimen for molecular profiling, liquid biopsy serves as a valuable complementary approach, underscoring the need for standardized quality metrics and faster turnaround times in clinical laboratories.
The original study
Clinical Utility of Next Generation Sequencing in Concurrent EBUS-TBNA and Liquid Biopsies in NSCLC.
- Authors
- Pastis NJ, Fox AH, Ferguson T, Gilbert CR, Thiboutot J, Tanner N, et al.
- Journal
- American journal of respiratory and critical care medicine
- Type
- Journal Article
- PMID
- 42475517
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.