{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T11:36:25Z","timestamp":1782732985557,"version":"3.54.5"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>In non-small cell lung cancer (NSCLC), [18F]FDG-PET\/CT is limited in pretherapeutic lymph node (LN) staging by false-positives. We previously demonstrated that a machine learning (ML) classifier using routine [18F]FDG-PET\/CT and clinical variables can improve diagnostic accuracy compared to visual assessment. The present study aimed at independent validation. Cohort 1 (Charit\u00e9) included 87 NSCLC patients (surgical and non-surgical), prospectively enrolled at our institution. Cohort 2 (TCIA) comprised 124 patients with primary surgery from the multi-institution NSCLC Radiogenomics dataset. Our ML classifier for differentiating N0\/1 vs. N2\/3 status was applied without modification. As comparator, the combined standard PET\/CT criterion of \u201cmediastinal LN uptake &gt; mediastinum and\/or short-axis &gt; 10 mm\u201d was used. Histology of N2\/3 LNs served as reference standard. Prevalence of pN2\/3 differed significantly between cohorts (Charit\u00e9: 40%, TCIA: 12%; p &lt; 0.001). Specificity was similar between ML and the standard PET\/CT criterion in the Charit\u00e9 cohort (65% vs. 60%; p = 0.5) but significantly higher with ML in TCIA (90% vs. 70%; p &lt; 0.001). Sensitivity for pN2\/3 was comparable between the two comparators in both the Charit\u00e9 cohort (97% each; p = 1.0) and TCIA (27% vs. 33%; p = 1.0). Lower sensitivity in TCIA patients reflects the preselection of surgical patients who had already been clinically staged and deemed suitable for surgery. The diagnostic performance of the ML classifier and its (potentially) superior specificity were thus successfully validated in two independent cohorts.<\/jats:p>","DOI":"10.3390\/curroncol32120679","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T17:35:17Z","timestamp":1764956117000},"page":"679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Independent Validation of a Machine Learning Classifier for Predicting Mediastinal Lymph Node Metastases in Non-Small Cell Lung Cancer Using Routinely Obtainable [18F]FDG-PET\/CT Parameters"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3529-3881","authenticated-orcid":false,"given":"Agata","family":"Wdowiak","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"Institute of Diagnostic and Interventional Radiology, Kantonsspital Aarau, 5001 Aarau, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0817-6532","authenticated-orcid":false,"given":"Julian M. M.","family":"Rogasch","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3046-0019","authenticated-orcid":false,"given":"Georg L.","family":"Baumg\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Radiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7452-7129","authenticated-orcid":false,"given":"Nikolaj","family":"Frost","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Pulmonary Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens-Carsten","family":"R\u00fcckert","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Vascular and Thoracic Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Neudecker","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Vascular and Thoracic Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6024-4312","authenticated-orcid":false,"given":"Sebastian","family":"Ochsenreither","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"},{"name":"Charit\u00e9 Comprehensive Cancer Center, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Gerhold","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\u2014Pneumology and Sleep Medicine, DRK Kliniken Berlin Mitte, 13359 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"Graff","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, DRK Kliniken Berlin Mitte, 13359 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4414-0657","authenticated-orcid":false,"given":"Holger","family":"Amthauer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Penzkofer","sequence":"additional","affiliation":[{"name":"Department of Radiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-7886","authenticated-orcid":false,"given":"Christian","family":"Furth","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"iv1","DOI":"10.1093\/annonc\/mdx222","article-title":"Early and Locally Advanced Non-Small-Cell Lung Cancer (NSCLC): ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"28","author":"Postmus","year":"2017","journal-title":"Ann. 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