CONCORDANCE OF ACTIONABLE MUTATIONS IN LIQUID BIOPSIES AND MATCHED TUMOR TISSUE OF BRAZILIAN NON-SMALL CELL LUNG CANCER (NSCLC)

Introduction: The detection of actionable mutations in liquid biopsies is currently emerging as a promising tool for treatment monitoring of non-small cell lung cancer (NSCLC) patients. Limited IVD options are currently available in the routine setting and sensitivity falls short. A highly sensitive multi-gene panel would be a valuable tool for precision medicine of NSCLC patients. Aim: To identify the concordance of actionable mutations in liquid biopsy samples and matched exome sequencing data from tumor tissue from Brazilian NSCLC patients. Methods: We isolated cell-free DNA (cfDNA) from plasma samples and paired tumor DNA (tDNA) from fresh-frozen tumor tissue from NSCLC patients (n=16; 50% adenocarcinoma; 50% squamous cell carcinoma). Fragment analysis of cfDNA was performed by TapeStation (Agilent D1000HS). We sequenced actionable mutations employing a NGS panel (Oncomine Lung cfDNA Cancer Assay) for 11 clinically relevant genes using the Ion Torrent platform. Sequencing data for cfDNA was analyzed by the IonReporter IR 5.10 software. Whole exome sequencing (WES) was performed using the Illumina platform employing tDNA. We assess the concordance of data from WES (tDNA) and from NGS panel (cfDNA). Results: Patients were staged on IIA (6.25%, n=1), IIIA (12.5%, n=2), IIIB (6.25%, n=1), and IV (75%, n=12), most patients (93.75%; n=15) were smokers or quitters. The median limit of detection (LOD) of NGS panel reached 0.11% for cfDNA samples. The concordance between the variants found in the cfDNA and tDNA was 90%. The concordant variants were distributed in the TP53 (p.G245C, p.G154V, p.H214R), KRAS (p.G12C, p.G12V), and PIK3CA (p.E542K) genes. Additional variants were only detected in cfDNA and not in matched tDNA for 68.75% of patients (n = 11) and they were distributed in the following genes: EGFR (p.V769_D770insASV, p.T790M), KRAS (p.G13D, p.G12C, p.Q61H, p.G12V), TP53 (p.T125T, p.R337L, p.V157F, p.Y220C, p.R282W, p.R249S, p.R273C), MAP2K1 (p.P124Q, p.E203K). The detection of variants in cfDNA but not in ctDNA suggests a broader analysis provided by liquid biopsies regardless of tumor heterogeneity. Conclusion: Multiplexed NGS panels can properly detect actionable mutations in liquid biopsies to assist treatment monitoring decreasing both tumor tissue biopsies and turnaround time for report release hastening therapeutic strategies to improve overall survival of NSCLC patients.