{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:36:29Z","timestamp":1790976989879,"version":"4.1.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","lungcancerjournal.info","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Lung Cancer"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.lungcan.2026.109468","type":"journal-article","created":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:36:44Z","timestamp":1779583004000},"page":"109468","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Efficacy and safety of immunotherapy in advanced pulmonary large-cell neuroendocrine carcinoma: A systematic review and meta-analysis"],"prefix":"10.1016","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-1964","authenticated-orcid":false,"given":"Akinari","family":"Tsukada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1012-2517","authenticated-orcid":false,"given":"Nozomu","family":"Tsurumaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-9048","authenticated-orcid":false,"given":"Naoki","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nokihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-5022","authenticated-orcid":false,"given":"Shinyu","family":"Izumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Hojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9","key":"10.1016\/j.lungcan.2026.109468_b0005","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1097\/JTO.0000000000000630","article-title":"The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification","volume":"10","author":"Travis","year":"2015","journal-title":"J. Thorac. Oncol."},{"issue":"8","key":"10.1016\/j.lungcan.2026.109468_b0010","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1097\/JTO.0000000000000589","article-title":"Pulmonary large-cell neuroendocrine carcinoma: from epidemiology to therapy","volume":"10","author":"Fasano","year":"2015","journal-title":"J. Thorac. Oncol."},{"issue":"2","key":"10.1016\/j.lungcan.2026.109468_b0015","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1183\/13993003.00618-2015","article-title":"Clinical features of large cell neuroendocrine carcinoma: a population-based overview","volume":"47","author":"Derks","year":"2016","journal-title":"Eur. Respir. J."},{"issue":"6","key":"10.1016\/j.lungcan.2026.109468_b0020","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01838-2016","article-title":"Chemotherapy for pulmonary large cell neuroendocrine carcinomas: does the regimen matter?","volume":"49","author":"Derks","year":"2017","journal-title":"Eur. Respir. J."},{"issue":"23","key":"10.1016\/j.lungcan.2026.109468_b0025","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1056\/NEJMoa1809064","article-title":"First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer","volume":"379","author":"Horn","year":"2018","journal-title":"N. Engl. J. Med."},{"issue":"10212","key":"10.1016\/j.lungcan.2026.109468_b0030","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(19)32222-6","article-title":"Durvalumab plus platinum\u2013etoposide versus platinum\u2013etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial","volume":"394","author":"Paz-Ares","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.lungcan.2026.109468_b0035","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.lungcan.2017.03.006","article-title":"PD-L1 expression in neuroendocrine tumors of the lung","volume":"108","author":"Tsuruoka","year":"2017","journal-title":"Lung Cancer"},{"issue":"14","key":"10.1016\/j.lungcan.2026.109468_b0040","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1158\/1078-0432.CCR-15-2946","article-title":"Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma\u2013like and non\u2013Small cell carcinoma\u2013like subsets","volume":"22","author":"Rekhtman","year":"2016","journal-title":"Clin. Cancer Res."},{"issue":"1","key":"10.1016\/j.lungcan.2026.109468_b0045","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1038\/s41467-018-03099-x","article-title":"Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors","volume":"9","author":"George","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.lungcan.2026.109468_b0050","article-title":"Study protocol of an open-label prospective phase II study of Durvalumab plus Carboplatin and Etoposide in advanced large cell neuroendocrine carcinoma of the lung (LOGIK2401: NECTAR study)","volume":"45","author":"Ishii","year":"2025","journal-title":"Cancer Treat. Res. Commun."},{"key":"10.1016\/j.lungcan.2026.109468_b0055","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"10.1016\/j.lungcan.2026.109468_b0060","article-title":"ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"issue":"4","key":"10.1016\/j.lungcan.2026.109468_b0065","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1136\/ebmental-2019-300117","article-title":"How to perform a meta-analysis with R: a practical tutorial","volume":"22","author":"Balduzzi","year":"2019","journal-title":"Evid. Based Ment. Health"},{"issue":"4","key":"10.1016\/j.lungcan.2026.109468_b0070","article-title":"Brief report on the efficacy of nivolumab in patients with previously treated advanced large-cell neuroendocrine cancer of the lung","volume":"2","author":"Agar","year":"2020","journal-title":"JTO Clin Res Rep."},{"key":"10.1016\/j.lungcan.2026.109468_b0075","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-001999","article-title":"Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung","volume":"9","author":"Dudnik","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.lungcan.2026.109468_b0080","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.3390\/biomedicines12061161","article-title":"The effectiveness of atezolizumab in metastatic large cell neuroendocrine carcinoma of the lungs: insights from the LANCE pilot study","volume":"12","author":"Evangelou","year":"2024","journal-title":"Biomedicines."},{"key":"10.1016\/j.lungcan.2026.109468_b0085","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.673901","article-title":"Comprehensive dissection of treatment patterns and outcome for patients with metastatic large-cell neuroendocrine lung carcinoma","volume":"11","author":"Fisch","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.lungcan.2026.109468_b0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.lungcan.2025.108830","article-title":"Treatment outcomes in patients with stage IV large cell neuroendocrine carcinoma: a nationwide registry study","volume":"210","author":"Heijboer","year":"2025","journal-title":"Lung Cancer"},{"key":"10.1016\/j.lungcan.2026.109468_b0095","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2025.1709544","article-title":"First-line immune checkpoint inhibitors combined with chemotherapy in advanced large-cell neuroendocrine carcinoma of the lung: a real-world retrospective study","volume":"15","author":"Ji","year":"2025","journal-title":"Front. Oncol."},{"key":"10.1016\/j.lungcan.2026.109468_b0100","article-title":"P3.13.28 Survival outcomes in advanced large cell neuroendocrine carcinoma of the lung in immunotherapy era: an NCDB analysis","volume":"20","author":"Karki","year":"2025","journal-title":"J. Thorac. Oncol."},{"issue":"19","key":"10.1016\/j.lungcan.2026.109468_b0105","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1097\/CM9.0000000000003233","article-title":"Immunotherapy combined with chemotherapy for patients with pulmonary large cell neuroendocrine carcinoma","volume":"137","author":"Li","year":"2024","journal-title":"Chin Med J (Engl)"},{"key":"10.1016\/j.lungcan.2026.109468_b0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.lungcan.2025.108698","article-title":"The survival analysis of stage III and IV inoperable lung large cell neuroendocrine carcinoma and the role of LIPI in immunological stratification","volume":"208","author":"Li","year":"2025","journal-title":"Lung Cancer"},{"key":"10.1016\/j.lungcan.2026.109468_b0115","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s12672-025-02071-8","article-title":"Efficacy and safety of immunotherapy plus chemotherapy in advanced or metastatic pulmonary large-cell neuroendocrine carcinoma","volume":"16","author":"Li","year":"2025","journal-title":"Discov. Oncol."},{"key":"10.1016\/j.lungcan.2026.109468_b0120","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2024.42.16_suppl.8602","article-title":"Comparison of chemotherapy to chemo-immunotherapy as first-line treatment in patients with advanced large cell neuroendocrine carcinomas (LCNECs) of mixed histology: a multi-institutional international retrospective study","volume":"42","author":"Matteson","year":"2024","journal-title":"J. Clin. Oncol."},{"issue":"17","key":"10.1016\/j.lungcan.2026.109468_b0125","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.7150\/jca.87052","article-title":"Enhanced efficacy of chemotherapy by addition of immune checkpoint inhibitors in stage IV large cell neuroendocrine carcinoma of the lung: a real-world analysis","volume":"14","author":"Meng","year":"2023","journal-title":"J. Cancer"},{"key":"10.1016\/j.lungcan.2026.109468_b0130","doi-asserted-by":"crossref","first-page":"9066","DOI":"10.1200\/JCO.2023.41.16_suppl.9066","article-title":"Efficacy and safety of PD-1\/PD-L1 inhibitor plus platinum-based chemotherapy vs. platinum-based chemotherapy alone in patients with previously untreated advanced large-cell neuroendocrine cancer of the lung","volume":"41","author":"Mu","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.lungcan.2026.109468_b0135","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000514841","article-title":"Efficacy and safety of anti-programed death-1 blockade in previously treated large-cell neuroendocrine carcinoma","volume":"66","author":"Naganuma","year":"2021","journal-title":"Chemotherapy"},{"issue":"1","key":"10.1016\/j.lungcan.2026.109468_b0140","doi-asserted-by":"crossref","first-page":"7717","DOI":"10.1038\/s41467-025-63091-0","article-title":"Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma","volume":"16","author":"Nassar","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.lungcan.2026.109468_b0145","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.lungcan.2020.03.008","article-title":"Efficacy of immune check-point inhibitors (ICPi) in large cell neuroendocrine tumors of lung (LCNEC)","volume":"143","author":"Sherman","year":"2020","journal-title":"Lung Cancer"},{"issue":"8","key":"10.1016\/j.lungcan.2026.109468_b0150","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.21037\/jtd-23-348","article-title":"Efficacy and safety of immune checkpoint inhibitors in lung large-cell neuroendocrine carcinoma","volume":"15","author":"Shi","year":"2023","journal-title":"J. Thorac. Dis."},{"issue":"4","key":"10.1016\/j.lungcan.2026.109468_b0155","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.cllc.2021.02.003","article-title":"Activity and immune correlates of programmed death-1 blockade therapy in patients with advanced large cell neuroendocrine carcinoma","volume":"22","author":"Shirasawa","year":"2021","journal-title":"Clin. Lung Cancer"},{"key":"10.1016\/j.lungcan.2026.109468_b0160","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1186\/s12885-023-10952-w","article-title":"Clinical activity of pembrolizumab with or without chemotherapy in advanced pulmonary large-cell and large-cell neuroendocrine carcinomas","volume":"23","author":"Song","year":"2023","journal-title":"BMC Cancer"},{"issue":"2","key":"10.1016\/j.lungcan.2026.109468_b0165","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1080\/07357907.2021.1988962","article-title":"Platinum doublet plus atezolizumab as first-line treatment in metastatic large cell neuroendocrine carcinoma: a single institution experience","volume":"40","author":"Vrontis","year":"2022","journal-title":"Cancer Invest."},{"issue":"10 Suppl 1","key":"10.1016\/j.lungcan.2026.109468_b0170","doi-asserted-by":"crossref","first-page":"S186","DOI":"10.1016\/j.jtho.2025.09.344","article-title":"P1.11.44 Efficacy and safety of immunotherapy as first-line treatment in metastatic pulmonary large-cell neuroendocrine carcinoma","volume":"20","author":"Yang","year":"2025","journal-title":"J. Thorac. Oncol."},{"key":"10.1016\/j.lungcan.2026.109468_b0175","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3892\/ol.2024.14268","article-title":"Efficacy of immune checkpoint inhibitors in advanced large cell neuroendocrine carcinoma of the lung: a single-institution experience","volume":"27","author":"Yan","year":"2024","journal-title":"Oncol. Lett."},{"issue":"22","key":"10.1016\/j.lungcan.2026.109468_b0180","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1056\/NEJMoa1801005","article-title":"Pembrolizumab plus chemotherapy in metastatic non\u2013small-cell lung cancer","volume":"378","author":"Gandhi","year":"2018","journal-title":"N. Engl. J. Med."},{"issue":"21","key":"10.1016\/j.lungcan.2026.109468_b0185","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1056\/NEJMoa1810865","article-title":"Pembrolizumab plus chemotherapy for squamous non\u2013small-cell lung cancer","volume":"379","author":"Paz-Ares","year":"2018","journal-title":"N. Engl. J. Med."},{"issue":"11","key":"10.1016\/j.lungcan.2026.109468_b0190","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1038\/s41591-022-01977-y","article-title":"Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial","volume":"28","author":"Gogishvili","year":"2022","journal-title":"Nat. Med."},{"issue":"6","key":"10.1016\/j.lungcan.2026.109468_b0195","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1093\/annonc\/mdt009","article-title":"Multicentre phase II study of cisplatin\u2013etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study","volume":"24","author":"Le Treut","year":"2013","journal-title":"Ann. Oncol."},{"issue":"7","key":"10.1016\/j.lungcan.2026.109468_b0200","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1097\/JTO.0b013e31828f6989","article-title":"Combination chemotherapy with irinotecan and cisplatin for large-cell neuroendocrine carcinoma of the lung: a multi-center phase II study","volume":"8","author":"Niho","year":"2013","journal-title":"J. Thorac. Oncol."},{"issue":"12","key":"10.1016\/j.lungcan.2026.109468_b0205","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1200\/JCO.20.02212","article-title":"Nivolumab and ipilimumab as maintenance therapy in extensive-disease small-cell lung cancer: CheckMate 451","volume":"39","author":"Owonikoko","year":"2021","journal-title":"J. Clin. Oncol."},{"issue":"4","key":"10.1016\/j.lungcan.2026.109468_b0210","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.jtho.2019.12.109","article-title":"Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 studies","volume":"15","author":"Chung","year":"2020","journal-title":"J. Thorac. Oncol."},{"issue":"12","key":"10.1016\/j.lungcan.2026.109468_b0215","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1001\/jama.2022.16464","article-title":"Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer: the ASTRUM-005 randomized clinical trial","volume":"328","author":"Cheng","year":"2022","journal-title":"J. Am. Med. Assoc."}],"container-title":["Lung Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0169500226005295?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0169500226005295?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T01:14:00Z","timestamp":1781140440000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0169500226005295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":43,"alternative-id":["S0169500226005295"],"URL":"https:\/\/doi.org\/10.1016\/j.lungcan.2026.109468","relation":{},"ISSN":["0169-5002"],"issn-type":[{"value":"0169-5002","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Efficacy and safety of immunotherapy in advanced pulmonary large-cell neuroendocrine carcinoma: A systematic review and meta-analysis","name":"articletitle","label":"Article Title"},{"value":"Lung Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lungcan.2026.109468","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"109468"}}