{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:09:06Z","timestamp":1791482946277,"version":"4.3.4"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T00:00:00Z","timestamp":1543276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>High-grade neuroendocrine carcinomas are rare in the gastrointestinal tract. However, treatment patterns and outcomes have not been well described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects, Materials, and Methods<\/jats:title>\n                    <jats:p>The National Cancer Database was analyzed. The primary objective was to describe the clinical outcomes and identify prognostic factors. Univariate and multivariate analyses were done to identify factors associated with patient outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1,861 patients were identified between 2004 and 2013. The mean age was 63 years (standard deviation \u00b113). The majority of the patients (78.1%) were non-Hispanic whites. The most common primary sites were pancreas (pancreatic neuroendocrine tumor [PNET] = 19.4%), large intestine (18.1%), esophagus (17.8%), and rectum (15.5%). Stage at presentation was I (6.6%), II (10.5%), III (18%) and IV (64.6%). Only 1.6% of the patients had brain metastases. Surgical resection was the primary therapy in 27.9%, and their median overall survival (OS) was 13.3 months. Patients treated with palliative chemotherapy had a median OS of 11.2 months, compared with 1.7 months for untreated patients. The median OS for high-grade PNET was 6 months, compared with 9.9 months for other high-grade gastrointestinal neuroendocrine carcinomas (HG GI NEC). On univariable analysis, age &amp;lt; 65 years (hazard ratio [HR] 0.72; 0.66\u20130.8; p &amp;lt; .001) and treatment at an academic center (HR 0.88; 0.79\u20130.99; p &amp;lt; .034) were associated with improved survival. Multivariable analysis confirmed prognostic advantage of treatment at an academic center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the largest series of HG GI NEC. Most patients present with metastatic disease, and overall survival remains poor. Treatment at an academic center, younger age, and use of chemotherapy were associated with improved survival. Multiagent chemotherapy was found to be associated with superior survival compared with single-agent chemotherapy, which was superior to no chemotherapy. Temporal sequences of chemotherapy, surgery, and radiation administration were not found to be associated with survival differences on multivariable analysis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2018-0382","type":"journal-article","created":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T16:05:19Z","timestamp":1543334719000},"page":"911-920","source":"Crossref","is-referenced-by-count":52,"title":["High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study"],"prefix":"10.1093","volume":"24","author":[{"given":"Olatunji B.","family":"Alese","sequence":"first","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Winship Research Informatics, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Shaib","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Akce","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhusmita","family":"Behera","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA"},{"name":"Winship Research Informatics, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassel F.","family":"El-Rayes","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,27]]},"reference":[{"key":"2021122507240794600_R1","first-page":"412","article-title":"Neuroendocrine differentiation in \"poorly differentiated\" colon carcinomas","volume":"56","author":"Staren","year":"1990","journal-title":"Am Surg"},{"key":"2021122507240794600_R2","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":"Garcia-Carbonero","year":"2016","journal-title":"Neuroendocrinology"},{"key":"2021122507240794600_R3","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":"2021122507240794600_R4","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1200\/JCO.2007.15.4377","article-title":"One hundred years after \"carcinoid\": 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":"2021122507240794600_R5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S1470-2045(07)70410-2","article-title":"Gastroenteropancreatic neuroendocrine tumours","volume":"9","author":"Modlin","year":"2008","journal-title":"Lancet Oncol"},{"key":"2021122507240794600_R6","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":"2021122507240794600_R7","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1097\/00000478-199011000-00003","article-title":"Neuroendocrine carcinoma of the colon and rectum. 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