{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:59:42Z","timestamp":1792789182953,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007387","name":"Fondazione Cassa di Risparmio di Pistoia e Pescia","doi-asserted-by":"publisher","award":["CaPoS"],"award-info":[{"award-number":["CaPoS"]}],"id":[{"id":"10.13039\/100007387","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CaPoS"],"award-info":[{"award-number":["CaPoS"]}],"id":[{"id":"https:\/\/ror.org\/05ahejj17","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Florence","award":["ex 60%"],"award-info":[{"award-number":["ex 60%"]}],"id":[{"id":"https:\/\/ror.org\/04jr1s763","id-type":"ROR","asserted-by":"crossref"}]},{"award":["ex 60%"],"award-info":[{"award-number":["ex 60%"]}],"id":[{"id":"https:\/\/ror.org\/04jr1s763","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background:\u00a0KRAS mutations are common oncogenic drivers in metastatic lung cancer (mLC) and may have prognostic and therapeutic implications. Circulating tumor DNA (ctDNA) analysis offers a minimally invasive approach for detecting tumor-specific alterations and monitoring tumor dynamics. This pilot study investigated the concordance between tissue and plasma KRAS mutational status and evaluated its clinical significance. Methods: Forty patients with mLC (25 males, 15 females; mean age 70.8 years) were included. KRAS mutations were analyzed in formalin-fixed paraffin-embedded tumor tissue using next-generation sequencing and in baseline plasma ctDNA using the Biocartis Idylla\u2122 system. Concordance was assessed using Cohen\u2019s kappa statistics. Associations with clinicopathological characteristics and survival outcomes (overall survival (OS), progression-free survival (PFS), and time to progression (TTP)) were examined. Longitudinal ctDNA monitoring was performed in a subset of patients. Results:\u00a0KRAS mutations were detected in 14\/36 (38.89%) of tumor tissues and 12\/40 (30.00%) of plasma samples, predominantly involving codon 12, with G12C as the most frequent variant. Tissue\u2013plasma concordance was assessed in the 36 patients with matched samples and was substantial (\u03ba = 0.64), while mutation subtype showed almost perfect agreement among concordant cases (percentage of agreement: 88.9%, \u03ba = 0.80, p = 0.002, 95% CI: 0.4400\u20131.0000). No significant associations were observed with clinicopathological variables. Longitudinal analysis revealed dynamic ctDNA changes, with molecular progression occasionally preceding clinical progression. Patients with KRAS-mutated ctDNA had shorter PFS and OS compared to those with wild-type ctDNA (median PFS: 134 vs. 146 days; median OS: 163 vs. 193 days). Conclusions: Plasma ctDNA detection of KRAS mutations identifies a poor-prognosis subgroup of mLC patients and provides dynamic insights into tumor evolution. Serial ctDNA monitoring may anticipate disease progression and support real-time assessment of treatment response, highlighting its potential role in translational research and precision oncology.<\/jats:p>","DOI":"10.3390\/cancers18183009","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:07:29Z","timestamp":1789574849000},"page":"3009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic Plasma KRAS ctDNA Profiling Identifies Treatment Response and Nascent Resistance in Metastatic Non-Small-Cell Lung Cancer: A Pilot Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Valentina","family":"Buzzi","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"},{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9389-6318","authenticated-orcid":false,"given":"Greta","family":"Berti","sequence":"additional","affiliation":[{"name":"Medical Oncology, S. Jacopo Hospital, 51100 Pistoia, Italy"},{"name":"Medical Oncology, S.S. Cosma e Damiano Hospital, 51017 Pescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0876-4521","authenticated-orcid":false,"given":"Michele","family":"Santillo","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"},{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Belli","sequence":"additional","affiliation":[{"name":"Pulmonology and Intensive Care Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4763-6395","authenticated-orcid":false,"given":"Elisabetta","family":"Rosi","sequence":"additional","affiliation":[{"name":"Pulmonology and Intensive Care Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Favarato","sequence":"additional","affiliation":[{"name":"Interventional Pulmonology Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3293-2123","authenticated-orcid":false,"given":"Federico","family":"Lavorini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"},{"name":"Pulmonology and Intensive Care Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tomassetti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"},{"name":"Interventional Pulmonology Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarosa","family":"Arcangeli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5136-5515","authenticated-orcid":false,"given":"Mauro","family":"Iannopollo","sequence":"additional","affiliation":[{"name":"Medical Oncology, S. Jacopo Hospital, 51100 Pistoia, Italy"},{"name":"Medical Oncology, S.S. Cosma e Damiano Hospital, 51017 Pescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-8973","authenticated-orcid":false,"given":"Elena","family":"Lastraioli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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