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This study aims to identify a population at high risk for BM in order to inform personalized follow\u2010up strategies in the future. We have therefore developed and validated a point\u2010based risk classifier for the risk of BM1 in patients with metastatic non\u2010oncogene\u2010addicted NSCLC without BM at disease onset. A total of 3139 patients were included from the German CRISP lung cancer registry and randomly assigned to a derivation and validation set (2:1). In the derivation set, a Fine and Gray model was developed considering BM and death competing risks. A point\u2010based risk classifier was derived and evaluated in the validation set. Of the baseline variables included in the risk model, \u22654 versus 0 extrathoracic metastatic sites (hazard ratio [HR], 2.69; 95% CI, 1.45\u20135.00), N3 vs. N0 disease (2.29; 1.41\u20133.72), and age\u2009&lt;\u200965 vs. \u226575\u2009years (2.03; 1.39\u20132.98) were the strongest predictors of BM development. Using the risk classifier, high\u2010risk patients in the derivation set had a cumulative incidence of BM of 23.7% (95% CI, 16.7\u201330.1) at 18\u2009months compared to 10.3% (8.9\u201311.7) in low\u2010risk patients (HR, 2.44; 95% CI, 1.87\u20133.19). In the validation set, the cumulative incidence of BM at 18\u2009months was 14.7% (11.5\u201317.8) and 8.9% (6.2\u201311.6) in the high\u2010risk and low\u2010risk groups, respectively (HR, 1.54; 95% CI, 1.08\u20132.20). In conclusion, our point\u2010based risk classifier is able to identify NSCLC patients at high risk for BM development that may benefit from intensified brain surveillance.<\/jats:p>","DOI":"10.1002\/ijc.70456","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T03:57:13Z","timestamp":1774324633000},"page":"739-749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prediction of the individual risk for the development of brain metastases in patients with non\u2010oncogene\u2010addicted non\u2010small cell lung cancer: Real\u2010world data from the German prospective\n                    <scp>CRISP<\/scp>\n                    registry (\n                    <scp>AIO<\/scp>\n                    \u2010\n                    <scp>TRK<\/scp>\n                    \u20100315)"],"prefix":"10.1002","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6207-0237","authenticated-orcid":false,"given":"Fabian","family":"Acker","sequence":"first","affiliation":[{"name":"Goethe University Frankfurt University Hospital, Department of Medicine 2, Hematology and Oncology  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Wenger","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital Institute of Neuroradiology  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reck","sequence":"additional","affiliation":[{"name":"LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research  Grosshansdorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius F.","family":"Waller","sequence":"additional","affiliation":[{"name":"Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Hoffknecht","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Niels\u2010Stensen\u2010Kliniken Franziskus Hospital Harderberg  Georgsmarienh\u00fctte Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Bethge","sequence":"additional","affiliation":[{"name":"Department of Pulmonology and Respiratory Medicine Clinic Bremen\u2010Ost  Bremen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnd","family":"Nusch","sequence":"additional","affiliation":[{"name":"MVZ f\u00fcr H\u00e4matologie und Onkologie  Ratingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Reiser","sequence":"additional","affiliation":[{"name":"Praxis Internistischer Onkologie und H\u00e4matologie  K\u00f6ln Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"Gemeinschaftspraxis f\u00fcr H\u00e4matologie &amp; 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