Dual NGS Comparative Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Samples of Non-Small Cell Lung Carcinoma (NSCLC)

SIMPLE SUMMARY: Precision oncology approaches patients in a personalized manner based on their own tumor molecular profile, which can be investigated nowadays by NGS assay. Regardless of their incidence, in many cancers, including NSCLC, tissue harvesting for analysis purposes is an issue. Therefore, alternative methods for analyzing tumor-derived genetic material, such as liquid biopsy, hold great potential in overcoming this disadvantage and opening personalization perspectives for these patients. The main aim of the current study was to distinguish the potential differences between the molecular landscapes found in the tumor tissue and in plasma samples harvested from patients with NSCLC by NGS. As a result, we validated the potential use of the Ion Torrent™ platform and technology for NGS of cfNAs in NSCLC using Oncomine™ Pan-Cancer Cell-Free Assay as a valuable tool for prospective NSCLC monitoring and therapy modulation in a dual tissue/plasma analysis setup. ABSTRACT: Lung cancer ranks second worldwide after breast cancer and third in Europe after breast and colorectal cancers when both sexes and all ages are considered. In this context, the aim of this study was to emphasize the power of dual analysis of the molecular profile both in tumor tissue and plasma by NGS assay as a liquid biopsy approach with impact on prognosis and therapy modulation in NSCLC patients. NGS analysis was performed both from tissue biopsies and from cfNAs isolated from peripheral blood samples. Out of all 29 different mutations detectable by both NGS panels (plasma and tumor tissue), seven different variants (24.13%; EGFR L858R in two patients, KRAS G13D and Q61H and TP53 G244D, V197M, R213P, and R273H) were detected only in plasma and not in the tumor itself. These mutations were detected in seven different patients, two of them having known distant organ metastasis. Our data show that NGS analysis of cfDNA could identify actionable mutations in advanced NSCLC and, therefore, this analysis could be used to monitor the disease progression and the treatment response and even to modulate the therapy in real time.