{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:13:41Z","timestamp":1780107221182,"version":"3.54.0"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:00:00Z","timestamp":1741996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biostatistics Shared Resource within the National Cancer Institute Center Core","award":["P30 CA012197-40"],"award-info":[{"award-number":["P30 CA012197-40"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data with the development of brain metastases. Methods: Patients with non-small-cell lung cancer (NSCLC) who underwent next-generation sequencing (NGS) were identified in our departmental database. iBMV was calculated by dividing the number of BMs by the interval of time between primary cancer and BM diagnosis. Two-sample t-testing was used to identify mutations statistically associated with iBMV (p &lt; 0.1). A value of +1 was assigned to each mutation with a positive association (\u201cdeleterious genes\u201d), and a value of \u22121 to each with an inverse association (\u201cprotective genes\u201d). The sum of these values was calculated to define iBMV risk scores of \u22121, 0 and 1. Pearson correlation test was used to determine the association between iBMV risk score and calculated iBMV, and a competing risk analysis assessed for death as a competing risk to the development of BMs. Results: A total of 312 patients were included in the analysis, 218 of whom (70%) developed brain metastases. \u201cDeleterious genes\u201d included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; \u201cprotective genes\u201d included ARAF, IDH1, MYC, and PTPN11. iBMV risk scores of 1, 0 and \u22121, predicted an 88%, 61% and 65% likelihood of developing a BM (p &lt; 0.01). A competing risk analysis found a significant association between iBMV risk scores of 1 vs. 0 and 1 vs. \u22121, and the likelihood of developing a BM using death as a competing risk. Overall survival (OS) at 1 and 2 years for patients with iBMV risk scores of 1, 0 and \u22121 was 72% vs. 84% vs. 85% and 46% vs. 69% vs. 70% (p &lt; 0.02). Conclusions: Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.<\/jats:p>","DOI":"10.3390\/cancers17060991","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T15:24:56Z","timestamp":1742225096000},"page":"991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genomic Signature for Initial Brain Metastasis Velocity (iBMV) in Non-Small-Cell Lung Cancer Patients: The Elusive Biomarker to Predict the Development of Brain Metastases?"],"prefix":"10.3390","volume":"17","author":[{"given":"Sarah E.","family":"Glynn","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-9253","authenticated-orcid":false,"given":"Claire M.","family":"Lanier","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel R.","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3550-8395","authenticated-orcid":false,"suffix":"Jr.","given":"Ralph","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Farris","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4429-2178","authenticated-orcid":false,"given":"Mohammed","family":"Abdulhaleem","sequence":"additional","affiliation":[{"name":"Department of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuezhu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Bioscience, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Bioscience, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-3315","authenticated-orcid":false,"given":"Jimmy","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9475-1558","authenticated-orcid":false,"given":"Thomas","family":"Lycan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William Jeffrey","family":"Petty","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina K.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Tatter","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4631-5476","authenticated-orcid":false,"given":"Adrian W.","family":"Laxton","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4891-498X","authenticated-orcid":false,"given":"Jaclyn J.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"Whitlow","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Soto-Pantoja","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-0764","authenticated-orcid":false,"given":"Fei","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corbin A.","family":"Helis","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA"},{"name":"Department of Radiation Oncology, Alexander T. Augusta Military Medical Center, Fort Belvoir, VA 22060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"vdaa041","DOI":"10.1093\/noajnl\/vdaa041","article-title":"Epidemiology of synchronous brain metastases","volume":"2","author":"Singh","year":"2020","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nec.2010.08.007","article-title":"Epidemiology of metastatic brain tumors","volume":"22","author":"Fox","year":"2011","journal-title":"Neurosurg. Clin. North Am."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Brenner, A.W., and Patel, A.J. (2022). Review of Current Principles of the Diagnosis and Management of Brain Metastases. Front. 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