Supervisors info:
Θεοχάρης Σταμάτιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πολίτη Αικατερίνη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κορκολοπούλου Πηνελόπη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Non-Small Cell Lung Cancer (NSCLC) except of being one of the most fatal tumor type is also the tumor types with the majority of approved targeted agents available. Next-generation sequencing (NGS) analysis is a robust technology that has been widely used for the detection of mutations in genes that can be used as biomarkers of response to treatment, such as EGFR, ALK, ROS1, BRAF, NTRK1,2 & 3, ERBB2, RET and MET.
1138 liquid biopsies had been tested since 2016 in Genekor. Specifically, 19% of the samples had sensitizing mutations of EGFR (Ex19del., P.L858R, p.G719X, p.L861Q, p.S768I), 1% of the samples had insensitizing mutations (Ex20Ins), 8% harbored the T790M resistance mutation in combination with other sensitizing mutations of EGFR and only in the 1% of the samples the T790M only had been detected. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 21 patients by both the cobas® and NGS platforms. In the 33 patients with concomitant tissue and liquid biopsy available, a total of 20 clinicaly relevant mutations were detected. Of them, 13 mutations were detected in both materials, 4 mutations were detected in tissue only and 3 mutations were detected in plasma only. Finally, the concordance of these two methods was 86% and the specificity and the sensitivity was 94,4% and 81,82% respectively. The main advantage of NGS over IVD is scalability for type of mutation and target gene.(e.g., the p.C797S resistance mutation ). Challenge of p.T790M detection in patients with acquired resistance to prior EGFR-TKI therapy due to genomic heterogeneity lead to efforts to optimize the experimental conditions to increase the sensitivity of p.T790M detection.
This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.
Keywords:
Lung cancer, Liquid biopsy, Targeted therapy, Resistance mutations, 1st and 3rd generation inhibitors, Immunotherapy
