{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:47:17Z","timestamp":1789577237555,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastroenteropancreatic poorly differentiated neuroendocrine carcinomas (GEP\u2010NECs) are aggressive cancers where cytotoxic chemotherapy is the backbone of treatment. While the addition of immunotherapy with immune checkpoint inhibitors (IOs) to chemotherapy is recommended for lung NECs, evidence regarding IO efficacy in GEP\u2010NECs is limited. We explore outcomes with systemic therapies in patients with metastatic GEP\u2010NECs using the National Cancer Database (NCDB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cases of metastatic GEP\u2010NECs with years of diagnosis between 2018 and 2022 were identified within the NCDB. Overall survival (OS) was analyzed using Kaplan\u2013Meier estimations and Cox proportional hazards regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four thousand one hundred twenty\u2010seven cases were included. 1209 (29.29%) patients did not receive any systemic therapy (chemotherapy\/immunotherapy\/both). Among the 2918 patients that received systemic therapy, 758 (25.98%) patients received immunotherapy (immunotherapy alone\u2009=\u200921; chemotherapy plus immunotherapy [chemoIO]\u2009=\u2009737). The percentage of patients receiving immunotherapy alongside chemotherapy increased from 12.27% in 2018 to 34.18% in 2022. Two thousand two hundred eighty cases were included for survival analysis. Patients treated with chemoIO (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009532) had prolonged OS versus chemotherapy alone (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091748), with median OS of 10.51 months vs. 8.31 months (HR, 0.77; 95% CI, 0.69\u20130.85;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u20090.001). The association was significant in all histological subgroups (small\u2010cell,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u20090.001; large\u2010cell,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04; others\/not specified,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combination chemoIO may improve survival in metastatic GEP\u2010NECs as compared to chemotherapy alone. Results of currently ongoing clinical trials exploring the role of immunotherapy in extrapulmonary NECs may help guide clinical practice in GEP\u2010NECs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71809","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:07:04Z","timestamp":1776064024000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Real World Outcomes With Chemotherapy and Immunotherapy in Metastatic Poorly Differentiated Gastroenteropancreatic Neuroendocrine Carcinomas"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1748-6508","authenticated-orcid":false,"given":"Rushabh","family":"Gujarathi","sequence":"first","affiliation":[{"name":"Department of Medicine University of Louisville  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Kwock","sequence":"additional","affiliation":[{"name":"University of Chicago Pritzker School of Medicine University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith","family":"Abodunrin","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Medicine University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namrata","family":"Setia","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0163-2635","authenticated-orcid":false,"given":"Xavier M.","family":"Keutgen","sequence":"additional","affiliation":[{"name":"Section of Endocrine Surgery, Department of Surgery University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Yi","family":"Liao","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Department of Medicine University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12022\u2010022\u201009708\u20102"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.15798"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0589"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","unstructured":"A.Mohamed M.Trybula S. L.Asa T. R.Halfdanarson andM. B.Sonbol \u201cManagement of Advanced High Grade Gastroenteropancreatic Neuroendocrine Neoplasms (GEP\u2010NENs): Comprehensive Review of the Current Literature \u201d31 no.10(2024):e240025 https:\/\/doi.org\/10.1530\/ERC\u201024\u20100025.","DOI":"10.1530\/ERC-24-0025"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12155138"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010025\u201003095\u20101"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100408"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01055"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2502099"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO\u201025\u201000363"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14163991"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2021.0032"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC\u201024\u20100231"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2023.101794"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC\u201018\u20100494"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.10.003"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.e14619"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809064"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13102448"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13975"},{"key":"e_1_2_10_22_1","volume-title":"International Classification of Diseases for Oncology (ICD\u2010O)","author":"World Health Organization","year":"2013"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12155138"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201015\u20100548"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.160771"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31124"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.3395"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2021.22.2.365"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102020\u2010001999"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.930491"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyab039"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010020\u201008602\u20107"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379\u2010018\u20100131\u20106"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71809","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.71809","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71809","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:10:09Z","timestamp":1777007409000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.71809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/cam4.71809"],"URL":"https:\/\/doi.org\/10.1002\/cam4.71809","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71809"}}