{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T19:19:28Z","timestamp":1793733568923,"version":"4.6.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2024,1,31]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Plasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK\u2122 Lung Panel (MassARRAY\u00ae technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>At least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR\u2009=\u20091.1, 95% CI\u2009=\u20090.55; 1.83, <jats:italic>P<\/jats:italic>\u2009=\u20090.980) and progression-free survival (PFS) (HR\u2009=\u20091.00, 95% CI\u2009=\u20090.57\u20131.76, <jats:italic>P<\/jats:italic>\u2009=\u20090.991). High PD-L1<jats:sup>+<\/jats:sup> sEV concentration was correlated with OS (HR\u2009=\u20091.14, 95% CI\u2009=\u20091.03\u20131.26, <jats:italic>P<\/jats:italic>\u2009=\u20090.016), but not with PFS (HR\u2009=\u20091.08, 95% CI\u2009=\u20090.99\u20131.18, <jats:italic>P<\/jats:italic>\u2009=\u20090.095). The interaction analysis suggested that PD-L1<jats:sup>+<\/jats:sup> sEV correlation with PFS changed in function of CTC presence\/absence (<jats:italic>P<\/jats:italic> interaction\u2009=\u20090.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1<jats:sup>+<\/jats:sup> sEV concentration (HR\u2009=\u20097.65, 95% CI\u2009=\u20093.11\u201318.83, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (<jats:italic>P<\/jats:italic>\u2009=\u20090.0001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>CTCs and high PD-L1<jats:sup>+<\/jats:sup> sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>NCT02866149, Registered 01 June 2015, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT02866149\">https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT02866149<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41416-023-02491-9","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T14:01:41Z","timestamp":1700143301000},"page":"63-72","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Circulating tumour cells and PD-L1-positive small extracellular vesicles: the liquid biopsy combination for prognostic information in patients with metastatic non-small cell lung cancer"],"prefix":"10.1038","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3489-2479","authenticated-orcid":false,"given":"Zahra","family":"Eslami-S","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Enrique","family":"Cort\u00e9s-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Sinoquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Gauthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Vautrot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Cayrefourcq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Avoscan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7834-061X","authenticated-orcid":false,"given":"William","family":"Jacot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Pouderoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Viala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin Dominique","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-159X","authenticated-orcid":false,"given":"Pierre-Jean","family":"Lamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Quantin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Gobbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6401-2903","authenticated-orcid":false,"given":"Catherine","family":"Alix-Panabi\u00e8res","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"2491_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. 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She received an honorarium from Menarini\u00a9. PJL is consultant in advisory boards for Agena Bioscience and AstraZeneca. He also received meeting travel support from Roche. WJ is in advisory boards Astra Zeneca, Eisai, BMS, Lilly France, Daiichi Sankyo, MSD, Novartis, Pfizer, Roche and Seagen and he received honoraria or payment from Astra Zeneca, Eisai, BMS, Lilly France, Daiichi Sankyo, MSD, Novartis, Pfizer, Roche and Seagen. WJ also received meeting travel support from Astra Zeneca, Novartis, Chugai Pharma, Pfizer, Eisai, Pierre Fabre, Glaxo Smithkline, Roche, Lilly France, Sanofi, and Aventis. The remaining authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All patients provided their written informed consent and were prospectively included in the ethics committee-approved ALCINA study (NCT02866149) that investigates the feasibility of assessing circulating tumour markers in blood in various early- or advanced-stage malignancies.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}