{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:24:15Z","timestamp":1789565055893,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T00:00:00Z","timestamp":1658016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["108-2314-B-182A-131"],"award-info":[{"award-number":["108-2314-B-182A-131"]}]},{"name":"Ministry of Science and Technology","award":["CMRPG3J1951"],"award-info":[{"award-number":["CMRPG3J1951"]}]},{"name":"Ministry of Science and Technology","award":["CMRPG5L0171"],"award-info":[{"award-number":["CMRPG5L0171"]}]},{"DOI":"10.13039\/501100005795","name":"Linkou Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["108-2314-B-182A-131"],"award-info":[{"award-number":["108-2314-B-182A-131"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Linkou Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3J1951"],"award-info":[{"award-number":["CMRPG3J1951"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Linkou Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG5L0171"],"award-info":[{"award-number":["CMRPG5L0171"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The impact of an initial skeletal-related event (SRE) and denosumab adjuvant treatment on the survival outcome of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with bone metastasis remains unclear. This retrospective study included 400 metastatic EGFR-mutated NSCLC patients. Among 190 bone metastasis patients, 61 had initial SREs and 73 received denosumab. We analyzed patient characteristics, SRE-free survival (SRE-FS), and overall survival (OS). In metastatic EGFR-mutated NSCLC, bone metastasis was associated with a poorer OS (21.7 vs. 33.0 months; p &lt; 0.001). Bone metastasis patients with initial SREs at diagnosis had an even shorter OS, compared with those without initial SRE (15.4 vs. 23.6 months; p = 0.026). Denosumab reduced SRE incidence (hazard ratio (HR) 0.57 (95% confidence interval (CI) 0.34\u20130.94; p = 0.027) and was associated with improved OS (26.6 vs. 20.1 months; p = 0.015). A multivariate analysis demonstrated that denosumab treatment was correlated with a lower incidence of SRE (HR 0.61 (95% CI 0.37\u20130.98); p = 0.042) and better OS (HR 0.60 (95% CI 0.41\u20130.88); p = 0.008). In subgroup analyses, denosumab prolonged SRE-FS (HR 0.36 (95% CI 0.19\u20130.79); p = 0.009) in patients without initial SREs and was related to a better OS (25.3 vs. 12.9 months; p = 0.016) in patients with initial or pre-existing SREs. Osteonecrosis of the jaw was diagnosed in two patients (2.74%) receiving denosumab. Our study confirmed the association between initial SREs and a worse outcome and provided novel evidence of the survival benefit of denosumab for EGFR-mutated NSCLC patients with bone metastasis.<\/jats:p>","DOI":"10.3390\/cancers14143470","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T21:00:28Z","timestamp":1658091628000},"page":"3470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Overall Survival Improvement in Patients with Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer and Bone Metastasis Treated with Denosumab"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6415-2965","authenticated-orcid":false,"given":"How-Wen","family":"Ko","sequence":"first","affiliation":[{"name":"Division of Thoracic Oncology, Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Tsun","family":"Chiu","sequence":"additional","affiliation":[{"name":"Institute of European and American Studies, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology, Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-1077","authenticated-orcid":false,"given":"Tsung-Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan"},{"name":"Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology, Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Teng","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology, Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Chuan","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Oncology Case Management, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3309-937X","authenticated-orcid":false,"given":"Chih-Hsi Scott","family":"Kuo","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology, Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2932-751X","authenticated-orcid":false,"given":"Chin-Chou","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary & Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-1244","authenticated-orcid":false,"given":"Muh-Hwa","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Division of Medical Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-1027","authenticated-orcid":false,"given":"Cheng-Ta","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology, Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Thoracic Medicine, Taoyuan Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.lungcan.2015.04.007","article-title":"The incidence and clinical impact of bone metastases in non-small cell lung cancer","volume":"89","author":"Kuchuk","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.lungcan.2018.05.006","article-title":"Association of molecular status and metastatic organs at diagnosis in patients with stage IV non-squamous non-small cell lung cancer","volume":"121","author":"Kuijpers","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1097\/JTO.0b013e31826aec2b","article-title":"Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: 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