Clinical feasibility of NGS liquid biopsy analysis in NSCLC patients

Autoři: Eirini Papadopoulou aff001;  Nikolaos Tsoulos aff001;  Katerina Tsantikidi aff001;  Vasiliki Metaxa-Mariatou aff001;  Pinelopi Eleftheria Stamou aff001;  Athina Kladi-Skandali aff001;  Evgenia Kapeni aff001;  Georgios Tsaousis aff001;  George Pentheroudakis aff002;  Dimitrios Petrakis aff002;  Dimitra Ioanna Lampropoulou aff004;  Gerasimos Aravantinos aff004;  Ioannis Varthalitis aff005;  George Kesisis aff006;  Ioannis Boukovinas aff007;  Pavlos Papakotoulas aff008;  Nikolaos Katirtzoglou aff009;  Elias Athanasiadis aff010;  Flora Stavridi aff011;  Christos Christodoulou aff012;  Anna Koumarianou aff013;  Yeşim Eralp aff014;  George Nasioulas aff001
Působiště autorů: GeneKor MSA, Athens, Greece aff001;  Department of Medical Oncology, School of Medicine, Ioannina, Greece aff002;  Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece aff003;  Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece aff004;  1st Oncology Department Henry Dunant Hospital Center, Athens, Greece aff005;  Oncology Department, Saint Luke Private Hospital, Thessaloniki, Greece aff006;  BioClinic Thessaloniki, Thessaloniki, Greece aff007;  First Department of Clinical Oncology, Theagenio Hospital, Thessaloniki, Greece aff008;  Euroclinic, Athens, Greece aff009;  Department of Medical Oncology, Mitera Hospital, Athens, Greece aff010;  Fourth Department of Medical Oncology, Hygeia Hospital, Athens, Greece aff011;  Second Department of Medical Oncology, Metropolitan Hospital, Athens, Greece aff012;  Hematology Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, Athens, Greece aff013;  Department of Medical Oncology, Istanbul University School of Medicine, İstanbul, Turkey aff014
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article



Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of "liquid biopsy" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy.


Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms.


At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients.


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.

Klíčová slova:

Biomarkers – Biopsy – Cancer treatment – Mutation – Mutation detection – Mutational analysis – Next-generation sequencing – Non-small cell lung cancer


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