{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:56Z","timestamp":1787028656012,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>\u00a0Background\/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of EP-NEC patients, their treatment responses, and survival outcomes. Methods: This retrospective observational study included 29 EP-NEC patients diagnosed and followed between 2015 and 2024. Clinical and demographic data, tumor localization, disease stage, administered treatments, and survival outcomes were analyzed. Kaplan\u2013Meier survival analysis was used to assess OS and PFS, with subgroup comparisons performed via the log-rank test. Results: The most common primary tumor sites were the pancreas (21%), prostate (17%), and cervix (14%). At diagnosis, 55.2% of patients had metastatic disease. First-line platinum-based chemotherapy achieved an objective response rate of 82.1%, with a median PFS of 8.16 months and a median OS of 14.16 months. Surgical intervention significantly improved survival (p = 0.020), while a high Ki-67 proliferation index (&gt;80%) was associated with worse PFS (p = 0.032). Other factors, including smoking status and liver-directed therapies, had no significant impact on survival. Conclusions: EP-NECs present with a poor prognosis despite platinum-based chemotherapy achieving high response rates. Surgical resection improves survival outcomes, whereas high Ki-67 expression is associated with a worse prognosis. These findings highlight the need for further research into novel therapeutic strategies for EP-NECs.<\/jats:p>","DOI":"10.3390\/jcm14072264","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T03:35:28Z","timestamp":1743132928000},"page":"2264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinicopathological Characteristics of Extrapulmonary Neuroendocrine Carcinomas: Treatment Responses and Survival Outcomes: Single-Center Experience"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9584-0827","authenticated-orcid":false,"given":"Harun","family":"Mu\u011flu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5194-1634","authenticated-orcid":false,"given":"Erdem","family":"S\u00fcnger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4587-0726","authenticated-orcid":false,"given":"Maral Martin","family":"M\u0131ldano\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-3630","authenticated-orcid":false,"given":"Ebru","family":"Engin Delipoyraz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-7204","authenticated-orcid":false,"given":"Mehmet Haluk","family":"Y\u00fccel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakan","family":"\u00d6z\u00e7elik","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5823-1704","authenticated-orcid":false,"given":"Jamshid","family":"Hamdard","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2715-4002","authenticated-orcid":false,"given":"\u00d6zg\u00fcr","family":"A\u00e7\u0131kg\u00f6z","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6mer Fatih","family":"\u00d6lmez","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zcan","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-6966","authenticated-orcid":false,"given":"Ahmet","family":"Bilici","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34214, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1097\/PAS.0b013e318159371c","article-title":"Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity?","volume":"32","author":"Shia","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1158\/1055-9965.EPI-10-0328","article-title":"Small intestinal cancer: A population-based study of incidence and survival patterns in the United States, 1992 to 2006","volume":"19","author":"Qubaiah","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ctrv.2008.10.007","article-title":"Clinical and therapeutic aspects of extrapulmonary small cell carcinoma","volume":"35","author":"Walenkamp","year":"2009","journal-title":"Cancer Treat. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/MPA.0b013e3181ebb56f","article-title":"The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas","volume":"39","author":"Strosberg","year":"2010","journal-title":"Pancreas"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1200\/JCO.2007.15.4377","article-title":"One hundred years after \u201ccarcinoid\u201d: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States","volume":"26","author":"Yao","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1758835920915299","DOI":"10.1177\/1758835920915299","article-title":"Second-line treatment in patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma: A systematic review and meta-analysis","volume":"12","author":"McNamara","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000443172","article-title":"ENETS consensus guidelines for high-grade gastroenteropancreatic neuroendocrine tumors and neuroendocrine carcinomas","volume":"103","author":"Sorbye","year":"2016","journal-title":"Neuroendocrinology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yoshimura, M., Seki, K., Bychkov, A., and Fukuoka, J. (2021). Molecular pathology of pulmonary large cell neuroendocrine carcinoma: Novel concepts and treatments. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.671799"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1038\/modpathol.3800659","article-title":"Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: A morphological, immunohistochemical, and molecular analysis","volume":"19","author":"Hiroshima","year":"2006","journal-title":"Mod. Pathol."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1038\/s41379-018-0110-y","article-title":"A common classification framework for neuroendocrine neoplasms: An International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal","volume":"31","author":"Rindi","year":"2018","journal-title":"Mod. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1093\/annonc\/mdw005","article-title":"Clinical correlation of extensive-stage small-cell lung cancer genomics","volume":"27","author":"Dowlati","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R219","DOI":"10.1530\/ERC-19-0483","article-title":"Extrapulmonary poorly differentiated NECs, including molecular and immune aspects","volume":"27","author":"McNamara","year":"2020","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1586\/17474124.2015.1092383","article-title":"Genetics of pancreatic neuroendocrine tumors: Implications for the clinic","volume":"9","author":"Pea","year":"2015","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ejca.2017.04.009","article-title":"Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort","volume":"79","author":"Walter","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1530\/ERC-15-0119","article-title":"Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms","volume":"22","author":"Heetfeld","year":"2015","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000493318","article-title":"Unmet needs in high-grade gastroenteropancreatic neuroendocrine neoplasms (WHO G3)","volume":"108","author":"Sorbye","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1158\/2159-8290.CD-21-0669","article-title":"Comprehensive genomic profiling of neuroendocrine carcinomas of the gastrointestinal system","volume":"12","author":"Yachida","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1158\/1078-0432.CCR-21-3058","article-title":"Expanding therapeutic opportunities for extrapulmonary neuroendocrine carcinoma","volume":"28","author":"Frizziero","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.21037\/tlcr-20-269","article-title":"New molecular classification of large cell neuroendocrine carcinoma and small cell lung carcinoma with potential therapeutic impacts","volume":"9","author":"Lantuejoul","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1097\/JTO.0000000000000663","article-title":"Introduction to the 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart","volume":"10","author":"Travis","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_22","unstructured":"Amin, M.B., Edge, S.B., Greene, F.L., Byrd, D.R., Brookland, R.K., Washington, M.K., Gershenwald, J.E., Compton, C.C., Hess, K.R., and Sullivan, D.C. (2017). AJCC Cancer Staging Manual, Springer."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/1097-0142(19910715)68:2<227::AID-CNCR2820680202>3.0.CO;2-I","article-title":"Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms","volume":"68","author":"Moertel","year":"1991","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1159\/000338794","article-title":"Comparison of chemotherapeutic treatment outcomes of advanced extrapulmonary neuroendocrine carcinomas and advanced small-cell lung carcinoma","volume":"96","author":"Terashima","year":"2012","journal-title":"Neuroendocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1111\/cas.12473","article-title":"Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system","volume":"105","author":"Yamaguchi","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e003956","DOI":"10.1136\/jitc-2021-003956","article-title":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma","volume":"10","author":"Govindan","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_28","first-page":"767","article-title":"Expression of ERCC1, Bcl-2, Lin28a, and Ki-67 as biomarkers of response to first-line platinum-based chemotherapy in patients with high-grade extrapulmonary neuroendocrine carcinomas or small cell lung cancer","volume":"11","author":"Braghiroli","year":"2017","journal-title":"Ecancermedicalscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/modpathol.2016.220","article-title":"Colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas","volume":"30","author":"Jesinghaus","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/cncr.22887","article-title":"Extrapulmonary small-cell carcinoma compared with small-cell lung carcinoma: A retrospective single-center study","volume":"110","author":"Cicin","year":"2007","journal-title":"Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/bjc.2016.229","article-title":"Molecular Profiling of Neuroendocrine Malignancies to \u0130dentify Prognostic and Therapeutic Markers: A Fox Chase Cancer Center Pilot Study","volume":"115","author":"Vijayvergia","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"67","DOI":"10.21037\/cco-23-79","article-title":"Advances in understanding and management of high-grade pancreatic neuroendocrine neoplasm: A comprehensive review","volume":"12","author":"Regalla","year":"2023","journal-title":"Chin. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Stef\u00e0no, E., De Castro, F., Ciccarese, A., Muscella, A., Marsigliante, S., Benedetti, M., and Fanizzi, F.P. (2024). An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168568"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Stumpo, S., Formelli, M.G., Persano, I., Parlagreco, E., Lauricella, E., Rodriquenz, M.G., Guerrera, L.P., Zurlo, I.V., Campana, D., and Brizzi, M.P. (2023). Extrapulmonary Neuroendocrine Carcinomas: Current Management and Future Perspectives. J. Clin. Med., 12.","DOI":"10.3390\/jcm12247715"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1158\/1078-0432.CCR-19-3356","article-title":"A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors","volume":"26","author":"Patel","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6958","DOI":"10.1158\/1078-0432.CCR-19-1133","article-title":"Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed\/Refractory Small-Cell Lung Cancer: Results from the Phase II TRINITY Study","volume":"25","author":"Morgensztern","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17588359231156870","DOI":"10.1177\/17588359231156870","article-title":"Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: A review","volume":"15","author":"Robinson","year":"2023","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Frizziero, M., Durand, A., Taboada, R.G., Zaninotto, E., Luchini, C., Chakrabarty, B., Hervieu, V., Claro, L.C.L., Zhou, C., and Cingarlini, S. (2021). Is the morphological subtype of extra-pulmonary neuroendocrine carcinoma clinically relevant?. Cancers, 13.","DOI":"10.3390\/cancers13164152"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s12672-022-00499-w","article-title":"Platinum-doublet chemotherapy for advanced gastroenteropancreatic neuroendocrine carcinoma: A systematic review and meta-analysis","volume":"13","author":"Ohmoto","year":"2022","journal-title":"Discov. Oncol."},{"key":"ref_40","first-page":"35","article-title":"A single center\u2019s experience of the extrapulmonary neuroendocrine carcinomas","volume":"9","author":"Celik","year":"2022","journal-title":"North. Clin. Istanb."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Weaver, J.M.J., Hubner, R.A., Valle, J.W., and McNamara, M.G. (2023). Selection of Chemotherapy in Advanced Poorly Differentiated Extra-Pulmonary Neuroendocrine Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15204951"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/MPA.0000000000001529","article-title":"Efficacy of Second-Line Chemotherapy in Extrapulmonary Neuroendocrine Carcinoma","volume":"49","author":"McGarrah","year":"2020","journal-title":"Pancreas"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cai, L., DeBerardinis, R.J., Xiao, G., Minna, J.D., and Xie, Y. (2022). A Pan-Cancer Assessment of RB1\/TP53 Co-Mutations. Cancers, 14.","DOI":"10.3390\/cancers14174199"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s00432-025-06126-9","article-title":"Patterns and outcomes of current antitumor therapy for high-grade neuroendocrine neoplasms: Perspective of a tertiary referral center","volume":"151","author":"Melhorn","year":"2025","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_45","unstructured":"Howlader, N., Noone, A., Krapcho, M., Garshell, J., Miller, D., and Altekruse, S. (2015). Surveillance, Epidemiology, and End Results (SEER) Program, NCI. SEER* Stat Database."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/annonc\/mds276","article-title":"Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): The NORDIC NEC study","volume":"24","author":"Sorbye","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_47","first-page":"15","article-title":"Multicenter retrospective analysis of systemic chemotherapy for advanced poorly differentiated neuroendocrine carcinoma of the digestive system","volume":"30","author":"Machida","year":"2012","journal-title":"Am. Soc. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s10350-003-0038-1","article-title":"Neuroendocrine carcinomas of the colon and rectum","volume":"47","author":"Bernick","year":"2004","journal-title":"Dis. Colon Rectum"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1245\/s10434-014-3725-3","article-title":"A retrospective review of 126 high-grade neuroendocrine carcinomas of the colon and rectum","volume":"21","author":"Smith","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_50","first-page":"1588","article-title":"Small cell carcinoma of the gallbladder: A case report and review of 53 cases in the literature","volume":"48","author":"Fujii","year":"2001","journal-title":"Hepatogastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1200\/JCO.2011.35.1817","article-title":"Prognostic validity of a novel American Joint Committee on Cancer Staging Classification for pancreatic neuroendocrine tumors","volume":"29","author":"Strosberg","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1093\/annonc\/mdq022","article-title":"Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): Results from the National Cancer Registry of Spain (RGETNE)","volume":"21","author":"Capdevila","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"54","DOI":"10.21037\/tgh.2019.12.18","article-title":"Novel immunotherapy strategies for treatment of neuroendocrine neoplasms","volume":"5","author":"Cives","year":"2020","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1530\/ERC-18-0494","article-title":"Immune checkpoint markers in gastroenteropancreatic neuroendocrine neoplasia","volume":"26","author":"Auernhammer","year":"2019","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/JCO.19.02105","article-title":"Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability\/mismatch repair\u2013deficient cancer: Results from the phase II KEYNOTE-158 study","volume":"38","author":"Marabelle","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1200\/JCO.2017.74.5471","article-title":"Safety and efficacy of pembrolizumab in advanced, programmed death ligand 1-positive cervical cancer: Results from the phase Ib KEYNOTE-028 trial","volume":"35","author":"Frenel","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1530\/ERC-20-0382","article-title":"Spartalizumab in metastatic, well\/poorly-differentiated neuroendocrine neoplasms","volume":"28","author":"Yao","year":"2021","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1530\/ERC-18-0100","article-title":"Preventive medicine of von Hippel\u2013Lindau disease-associated pancreatic neuroendocrine tumors","volume":"25","author":"Krauss","year":"2018","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/s00423-001-0274-6","article-title":"Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN 1","volume":"386","author":"Hessman","year":"2002","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.annonc.2020.03.304","article-title":"Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Pavel","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_61","first-page":"15","article-title":"Randomized phase III study of etoposide plus cisplatin versus irinotecan plus cisplatin in advanced neuroendocrine carcinoma of the digestive system: A Japan Clinical Oncology Group study (JCOG1213)","volume":"33","author":"Morizane","year":"2015","journal-title":"Am. Soc. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"100119","DOI":"10.1016\/j.esmoop.2021.100119","article-title":"Capecitabine plus temozolomide in patients with grade 3 unresectable or metastatic gastroenteropancreatic neuroendocrine neoplasms with Ki-67 index < 55%: Single-arm phase II study","volume":"6","author":"Jeong","year":"2021","journal-title":"ESMO Open"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/oncolo\/oyab039","article-title":"Survival according to primary tumor location, stage, and treatment patterns in locoregional gastroenteropancreatic high-grade neuroendocrine carcinomas","volume":"27","author":"Dasari","year":"2022","journal-title":"Oncologist"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/7\/2264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:02:22Z","timestamp":1760029342000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/7\/2264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,26]]},"references-count":63,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["jcm14072264"],"URL":"https:\/\/doi.org\/10.3390\/jcm14072264","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,26]]}}}