{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:12:20Z","timestamp":1771560740868,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T00:00:00Z","timestamp":1622332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Analysis of circulating tumor DNA (ctDNA) has remarkable potential as a non-invasive lung cancer molecular diagnostic method. This prospective study addressed the clinical value of a targeted-gene amplicon-based plasma next-generation sequencing (NGS) assay to detect actionable mutations in ctDNA in patients with newly diagnosed advanced lung adenocarcinoma. Methods: ctDNA test performance and concordance with tissue NGS were determined, and the correlation between ctDNA findings, clinical features, and clinical outcomes was evaluated in 115 patients with paired plasma and tissue samples. Results: Targeted-gene NGS-based ctDNA and NGS-based tissue analysis detected 54 and 63 genomic alterations, respectively; 11 patients presented co-mutations, totalizing 66 hotspot mutations detected, 51 on both tissue and plasma, 12 exclusively on tissue, and 3 exclusively on plasma. NGS-based ctDNA revealed a diagnostic performance with 81.0% sensitivity, 95.3% specificity, 94.4% PPV, 83.6% NPV, test accuracy of 88.2%, and Cohen\u2019s Kappa 0.764. PFS and OS assessed by both assays did not significantly differ. Detection of ctDNA alterations was statistically associated with metastatic disease (p = 0.013), extra-thoracic metastasis (p = 0.004) and the number of organs involved (p = 0.010). Conclusions: This study highlights the potential use of ctDNA for mutation detection in newly diagnosed NSCLC patients due to its high accuracy and correlation with clinical outcomes.<\/jats:p>","DOI":"10.3390\/cancers13112707","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:22:15Z","timestamp":1622420535000},"page":"2707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical Application of Next-Generation Sequencing of Plasma Cell-Free DNA for Genotyping Untreated Advanced Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-0770","authenticated-orcid":false,"given":"Maria Gabriela O.","family":"Fernandes","sequence":"first","affiliation":[{"name":"Pulmonology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5934-5201","authenticated-orcid":false,"given":"Nat\u00e1lia","family":"Cruz-Martins","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"},{"name":"Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Concei\u00e7\u00e3o","family":"Souto Moura","sequence":"additional","affiliation":[{"name":"Pathology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Susana","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"},{"name":"Pathology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Joana","family":"Pereira Reis","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"}]},{"given":"Ana","family":"Justino","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Pina","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"}]},{"given":"Adriana","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Pulmonology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Henrique","family":"Queiroga","sequence":"additional","affiliation":[{"name":"Pulmonology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Jos\u00e9 Carlos","family":"Machado","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"}]},{"given":"Venceslau","family":"Hespanhol","sequence":"additional","affiliation":[{"name":"Pulmonology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7132-4094","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Costa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1200\/JCO.2017.76.7293","article-title":"Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists\/International Association for the Study of 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