{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T02:53:53Z","timestamp":1788836033987,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Bone metastases (BMs) were reported in &lt;15% of cases of neuroendocrine neoplasms (NENs). Their clinical behavior is various and clinical management is still undefined. This study aimed to describe the clinical practical management and survival outcome of neuroendocrine neoplasm patients with BMs. This is a retrospective, observational, multicenter, nationwide study, in which clinical\u2010pathological characteristics, diagnostic tools, skeletal\u2010related events (SREs), bone targeted agents (BTAs) and their correlation with clinical outcome were collected. Data from 320 patients from 18 Italian centers diagnosed with bone metastases during 2000\u20132013 were captured. Most patients had a well\/moderately differentiated NEN, with synchronous distant metastases, mostly hepatic, the majority of which originated from a gastroenteropancreatic primary site. Bone was the first metastatic site in 41% of patients. After a median follow\u2010up of 27\u2009months 122 patients died. The median overall survival (OS) was 62\u2009months. In 22% of patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200972), SREs were observed, and 31% of patients received a BTA. At multivariable analysis of factors associated with OS after the development of BMs, primary lung site, Ki\u201067 \u226555% versus \u226420%, &gt;10 BMs, mixed pattern (osteoblastic\/osteolytic) versus osteoblastic, prior lung metastases and SREs were found to be significant poor prognosis factors. At multivariable analysis Ki\u201067 \u226555% versus \u226420% remains significantly associated with the development of SREs. Our study represents a real\u2010life nationwide scenario of a large series of NEN patients with BMs handled at dedicated centers. Several hypotheses generated by this study are warranted to be tested in future homogeneous studies, including objective criteria for the use of BTAs.\n                  <\/jats:p>","DOI":"10.1111\/jne.70115","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T07:35:22Z","timestamp":1763537722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bone metastases from neuroendocrine neoplasms: Results of an Italian nationwide survey of natural history and management"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-0704","authenticated-orcid":false,"given":"Nicola","family":"Fazio","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology, IEO, IRCCS, ENETS and EURACAN NEN Center of Excellence  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Maisonneuve","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Biostatistics European Institute of Oncology, IEO, IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Frezza","sequence":"additional","affiliation":[{"name":"Medical Oncology 2 Fondazione IRCCS Istituto Nazionale Tumori  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Ranallo","sequence":"additional","affiliation":[{"name":"Osteoncology and Rare Tumors Center IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)  Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Osteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies IRCCS Istituto Ortopedico Rizzoli  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"La Salvia","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology S. Luigi Gonzaga Hospital  Orbassano Italy"},{"name":"National Center for Drug Research and Evaluation National Institute of Health (Istituto Superiore Di Sanit\u00e0)  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Brizzi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology S. Luigi Gonzaga Hospital  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"De Divitiis","sequence":"additional","affiliation":[{"name":"UOSD oncologia AOU San Giovanni di Dio e Ruggi D'aragona  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Tafuto","sequence":"additional","affiliation":[{"name":"Sarcomas and Rare Tumors Unit ENETS Center of Excellence, Istituto Nazionale Tumori \u2013 I.R.C.C.S. Fondazione \u2018G.Pascale\u2019  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Pusceddu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Marconcini","sequence":"additional","affiliation":[{"name":"Oncology Department Azienda Ospedaliera Universitaria S. Chiara  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-1816","authenticated-orcid":false,"given":"Mauro","family":"Cives","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine University of Bari  Bari Italy"},{"name":"Division of Medical Oncology A.O.U. Consorziale Policlinico di Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Interdisciplinary Department of Medicine (DIM) University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Campana","sequence":"additional","affiliation":[{"name":"Medical Oncology Policlinico S. Orsola  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"De Lisi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Santa Chiara Hospital  Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"Medical\u2010Surgical Sciences and Biotechnology La Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9324-3946","authenticated-orcid":false,"given":"Antongiulio","family":"Faggiano","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"},{"name":"Endocrinology and Andrology Unit, Department of Clinical and Molecular Medicine AOU S. Andrea, \u201cLa Sapienza\u201d University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3768-5803","authenticated-orcid":false,"given":"Roberta","family":"Modica","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Massironi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery Vita e Salute San Raffaele University  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Endocrinology Policlinico Gemelli  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Panzuto","sequence":"additional","affiliation":[{"name":"Digestive Disease Unit 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