{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:41:56Z","timestamp":1792453316952,"version":"4.5.0"},"reference-count":86,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2180-390900677"],"award-info":[{"award-number":["EXC 2180-390900677"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["487-0-0"],"award-info":[{"award-number":["487-0-0"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Junior Clinician Scientist Program of the Medical Faculty of the University Tuebingen","award":["EXC 2180-390900677"],"award-info":[{"award-number":["EXC 2180-390900677"]}]},{"name":"Junior Clinician Scientist Program of the Medical Faculty of the University Tuebingen","award":["487-0-0"],"award-info":[{"award-number":["487-0-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Neuroendocrine neoplasms (NENs) represent a rare and heterogenous group of tumors with predominantly gastroenteropancreatic or pulmonary origin. Despite numerous diagnostic efforts, the primary tumor site remains unknown in up to 20% of the patients diagnosed with NEN. In this subgroup of NEN patients, a standard diagnostic algorithm has not yet been integrated into clinical routine. Of note, an undetermined primary tumor site in NENs is associated with an impaired clinical outcome by at least \u201cformally\u201d limiting treatment options exclusively approved for NENs of a certain histological origin. In this retrospective study, a patient cohort of 113 patients initially diagnosed with NEN of unknown primary (NEN-UP) was analyzed. In 13 patients (11.5%) a primary tumor site could be identified subsequently, amongst others, by performing somatostatin receptor (SSTR)-PET-based imaging, which was irrespective of the initial clinical or demographic features. Diagnostic work-up and therapeutic regimens did not differ significantly between patients with an identified or unidentified primary tumor site; only a detailed immunohistochemical assessment providing additional information on the tumor origin proved to be significantly associated with the detection of a primary tumor site. Our study revealed that a profound diagnostic work-up, particularly including SSTR-PET-based imaging, leads to additional treatment options, finally resulting in significantly improved clinical outcomes for patients with NEN-UPs.<\/jats:p>","DOI":"10.3390\/cancers15174316","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:51:14Z","timestamp":1693299074000},"page":"4316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance\u2014A Retrospective, Long-Term Single-Center Experience"],"prefix":"10.3390","volume":"15","author":[{"given":"Moritz","family":"Schmidt","sequence":"first","affiliation":[{"name":"Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany"},{"name":"ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany"},{"name":"DFG Cluster of Excellence 2180 \u2018Image-Guided and Functional Instructed Tumor Therapy\u2019 (iFIT), University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Hinterleitner","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany"},{"name":"ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany"},{"name":"DFG Cluster of Excellence 2180 \u2018Image-Guided and Functional Instructed Tumor Therapy\u2019 (iFIT), University of Tuebingen, 72076 Tuebingen, Germany"},{"name":"Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Singer","sequence":"additional","affiliation":[{"name":"ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany"},{"name":"Department of Pathology, University Hospital Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich M.","family":"Lauer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany"},{"name":"ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany"},{"name":"DFG Cluster of Excellence 2180 \u2018Image-Guided and Functional Instructed Tumor Therapy\u2019 (iFIT), University of Tuebingen, 72076 Tuebingen, Germany"},{"name":"German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Zender","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany"},{"name":"ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany"},{"name":"DFG Cluster of Excellence 2180 \u2018Image-Guided and Functional Instructed Tumor Therapy\u2019 (iFIT), University of Tuebingen, 72076 Tuebingen, Germany"},{"name":"German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Hinterleitner","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany"},{"name":"ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany"},{"name":"DFG Cluster of Excellence 2180 \u2018Image-Guided and Functional Instructed Tumor Therapy\u2019 (iFIT), University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00423-011-0739-1","article-title":"The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors","volume":"396","author":"Schimmack","year":"2011","journal-title":"Langenbecks Arch. 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