{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:12:44Z","timestamp":1789139564304,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Poorly differentiated neuroendocrine carcinomas (NECs) are rare malignancies with a dismal prognosis, few therapeutic options, and a lack of predictive factors. We describe a large series of extra\u2010pulmonary (EP) NEC patients from a neuroendocrine neoplasm (NEN) referral center, aiming to improve the clinical management of these diseases. Medical records of patients with histological diagnosis of pure histology EP\u2010NEC, discussed at the NEN\u2010dedicated multidisciplinary team (MDT) between October 2018 and August 2022, were included. Demographic features, tumor characteristics, molecular profile, treatments, and responses to treatments were collected. Among 1594 NEN diagnoses discussed at the MDT during the study period, 377 were NECs; the final population consisted of 173 patients, mostly presenting with advanced disease and often with a gastroenteropancreatic tract primary tumor. Molecular profiling was available for 52 patients (30%). The most frequent alterations occurred in\n                    <jats:italic>TP53<\/jats:italic>\n                    and\n                    <jats:italic>KRAS<\/jats:italic>\n                    . One of 25 patients tested for microsatellite instability was confirmed MSI\u2010h; one of 52 patients tested had a high tumor mutational burden (TMB\u2009=\u200919). Median overall survival (OS) was 15.4\u2009months (95% confidence interval [CI]: 13.2\u201318.5). Most patients with advanced disease received a first\u2010line chemotherapy (136\/153 [88.9%]), often platinum plus etoposide (111\/136 patients [82%]). The overall response rate (ORR) to first\u2010line was 40%. Median progression\u2010free survival (PFS) was 5.7\u2009months (95% CI: 4.4\u20136.4). Forty\u2010two percent and 18% of patients received second\u2010 and third\u2010line therapy, respectively. No significant difference was seen when stratifying OS and PFS by Ki\u201067 groups and tumor cell morphology, whereas performance status and presence of metastases were significantly related to OS. In this single\u2010center retrospective large series of EP\u2010NECs, almost half of the patients showed a tumor response to first\u2010line chemotherapy. No relevant correlation was found with primary site, tumor cell morphology, or Ki\u201067. The proportion of patients receiving subsequent lines, along with the mOS, confirms the aggressiveness of this disease. Molecular profiling was performed only fragmentarily, with limited practical applicability. Efforts shall be made in the future to implement these investigations.\n                  <\/jats:p>","DOI":"10.1111\/jne.70057","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T02:40:20Z","timestamp":1750300820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical\/pathological features and survival outcomes of extra\u2010pulmonary neuroendocrine carcinomas: A retrospective single\u2010center series"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0213-6538","authenticated-orcid":false,"given":"L.","family":"Benini","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology, IEO, IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Gervaso","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology, IEO, IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Frassoni","sequence":"additional","affiliation":[{"name":"Department of Statistics and Quantitative Methods University of Milano\u2010Bicocca  Milan Italy"},{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Bagnardi","sequence":"additional","affiliation":[{"name":"Department of Statistics and Quantitative Methods University of Milano\u2010Bicocca  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. A.","family":"Cella","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology, IEO, IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Algeri","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Ciardiello","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology, IEO, IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. G.","family":"Zampino","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology, IEO, IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Winchler","sequence":"additional","affiliation":[{"name":"Clinical Oncology Unit Careggi University Hospital  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Boselli","sequence":"additional","affiliation":[{"name":"Data Management\u2010Clinical Trial Office Scientific Direction, European Institute of Oncology (IEO) IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Data Management\u2010Clinical Trial Office Scientific Direction, European Institute of Oncology (IEO) IRCCS  Milan 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