{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:57:19Z","timestamp":1792270639269,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972189"],"award-info":[{"award-number":["81972189"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172623"],"award-info":[{"award-number":["82172623"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The prognosis of non\u2013small\u2010cell lung cancer (NSCLC) with leptomeningeal metastasis (LM) is poor. Detection of cell\u2010free DNA (cfDNA) by next generation sequencing (NGS) in cerebrospinal fluid (CSF) may facilitate diagnosis of LM and identification of drug resistance mechanisms, yet its clinical use needs to be further verified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective cohort study to assess the genetic profiles of paired CSF and plasma samples in lung cancer patients with LM. Of 17 patients screened, a total of 14 patients with LM and paired NGS tests were enrolled.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients harbor driver gene mutations, including 12 epidermal growth factor receptor (EGFR) activating mutations, 1 anaplastic lymphoma kinase (ALK) rearrangement, and 1 ROS\u20101 fusion. Genetic mutations were detected in CSF cfDNA from 92.9% patients (13\/14), which was significantly higher than that from the plasma (9\/14, 64.2%). The mutations were highly divergent between CSF and plasma cfDNA, with a concordance rate of 24.38% and 10 mutations shared by the two media. CSF cfDNA could also benefit the analysis of resistance mechanisms to targeted therapies. In five patients who experienced progression on 1st or 2nd generation EGFR\u2010tyrosine kinase inhibitors (TKIs), RB1 mutation, and amplification of <jats:italic>MET<\/jats:italic> and <jats:italic>EGFR<\/jats:italic> were detected in CSF cfDNA only. In eight patients with LM progression on osimertinib resistance, <jats:italic>EGFR<\/jats:italic> amplification was detected in CSF cfDNA from four patients, whereas no CNVs were detected in the matched plasma samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, CSF could be superior to plasma in providing a more comprehensive genetic landscape of LM to find out drug resistance mechanisms and guide subsequent treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.14592","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T23:54:41Z","timestamp":1658966081000},"page":"2574-2583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genotyping of cerebrospinal fluid in lung cancer patients with leptomeningeal 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