{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:03:28Z","timestamp":1784127808570,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brain metastases are a major contributor to morbidity and mortality in patients with advanced solid tumors; however, early detection and accurate prognostic assessment remain significant clinical challenges. ctDNA is a minimally invasive biomarker that allows real\u2010time monitoring of tumor behavior and provides information on systemic tumor burden and molecular diversity. This study aimed to systematically evaluate the diagnostic and prognostic value of ctDNA in brain metastases, with particular emphasis on the complementary roles of plasma and CSF ctDNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Embase, Cochrane Library, Web of Science, and ScienceDirect were systematically searched up to January 2025. Pooled ORs, SMDs, and HRs with 95% CIs were calculated using fixed\u2010effects or random\u2010effects models according to heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifteen studies (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091763) were included. ctDNA positivity was significantly associated with increased risk of brain metastases (OR\u2009=\u20091.67, 95% CI: 1.24\u20132.26,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Subgroup analysis showed that NGS had notably higher predictive performance (OR\u2009=\u20095.50, 95% CI: 1.92\u201315.76,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Plasma ctDNA levels were significantly higher in patients with brain metastases (SMD\u2009=\u20090.51, 95% CI: 0.18\u20130.84,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Notably, CSF ctDNA positivity was strongly associated with worse overall survival (HR\u2009=\u20092.75, 95% CI: 1.75\u20134.32,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Plasma ctDNA serves as a non\u2010invasive biomarker for systemic metastatic risk, whereas CSF ctDNA provides superior prognostic value for intracranial disease. Using these biomarkers together in a clinical workflow could enhance risk assessment and guide treatment decisions in patients with brain metastases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70965","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:09:02Z","timestamp":1780495742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Circulating Tumor\n                    <scp>DNA<\/scp>\n                    With Brain Metastases: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8208-5807","authenticated-orcid":false,"given":"Shaobo","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City)  Changde Hunan 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