{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T03:19:15Z","timestamp":1792293555500,"version":"4.4.0"},"reference-count":33,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: Neuroendocrine tumors (NETs) are rare malignancies with different prognoses. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective but beyond them few treatment options are available. We evaluated the clinical efficacy of 177 Lu-DOTATATE in patients with progressive metastatic F-NETs and SSA-refractory syndrome. Patients and Methods: A non-pre-planned joint analysis was conducted in patients enrolled in phase II clinical trials on metastatic NETs. We extrapolated data from F-NET patients with \u22651 refractory sign\/symptom to octreotide, and \u22651 measurable lesion. Syndrome response (SR), overall survival (OS), progression-free survival (PFS), tolerance and disease response were analyzed. Results: Sixty-eight patients were enrolled, the majority (88.1%) with a SR. According to RECIST criteria, 1 (1.5%) patient showed a CR, 21 (32.3%) had a PR and 40 (61.5%) SD. At a median follow-up of 28.9 months (range 2.2\u201363.2) median PFS was 33.0 months (95%CI: 27.1\u201348.2). Median OS (mOS) had not been reached at the time of the analysis; the 2-year OS was 87.8% (95%CI: 76.1\u201394.1). Syndromic responders showed better survival than non-responders, with a 2-year OS of 93.9% (95%CI: 92.2\u201398.0) vs. 40.0% (95%CI: 6.6\u201373.4), respectively. A total of 233 adverse events were recorded. Grade 1\u20132 hematological toxicity was the most frequent. Conclusion: The 177 Lu-DOTATATE improved symptoms and disease control in patients with F-NETs. Treatment was well tolerated. The syndrome had an impact on both quality of life and OS.<\/jats:p>","DOI":"10.3390\/cancers14246022","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T05:50:52Z","timestamp":1670392252000},"page":"6022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["177Lu-DOTATATE Efficacy and Safety in Functioning Neuroendocrine Tumors: A Joint Analysis of Phase II Prospective Clinical Trials"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3845-4687","authenticated-orcid":false,"given":"Alberto","family":"Bongiovanni","sequence":"first","affiliation":[{"name":"Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0259-4167","authenticated-orcid":false,"given":"Toni","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Osteoncologia, Sarcomi dell\u2019Osso e dei Tessuti Molli, e Terapie Innovative, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5529-4769","authenticated-orcid":false,"given":"Flavia","family":"Foca","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Sansovini","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Di Paolo","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Grassi","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Liverani","sequence":"additional","affiliation":[{"name":"Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3388-2217","authenticated-orcid":false,"given":"Chiara","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-7339","authenticated-orcid":false,"given":"Nicoletta","family":"Ranallo","sequence":"additional","affiliation":[{"name":"Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-6253","authenticated-orcid":false,"given":"Federica","family":"Matteucci","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Paganelli","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-0681","authenticated-orcid":false,"given":"Stefano","family":"Severi","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1053\/j.gastro.2005.03.038","article-title":"Current status of gastrointestinal carcinoids","volume":"128","author":"Modlin","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1001\/jamaoncol.2017.0589","article-title":"Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States","volume":"3","author":"Dasari","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/cncr.29099","article-title":"Exploring the rising incidence of neuroendocrine tumors: A population-based analysis of epidemiology, metastatic presentation, and outcomes: 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