{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:25:54Z","timestamp":1772119554471,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2023,12]]},"DOI":"10.1007\/s10637-023-01399-8","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T03:02:53Z","timestamp":1697684573000},"page":"777-786","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimal first-line treatment strategies of systemic therapy for unresectable gastrointestinal neuroendocrine tumors based on the opinions of Japanese experts."],"prefix":"10.1007","volume":"41","author":[{"given":"Yoshitaka","family":"Honma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susumu","family":"Hijioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigemi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuhide","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junji","family":"Furuse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"1399_CR1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s12885-020-07581-y","volume":"20","author":"T Masui","year":"2020","unstructured":"Masui T, Ito T, Komoto I et al (2020) Recent epidemiology of patients with gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) in Japan: a population-based study. BMC Cancer 20:104","journal-title":"BMC Cancer"},{"key":"1399_CR2","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1001\/jamaoncol.2017.0589","volume":"3","author":"A Dasari","year":"2017","unstructured":"Dasari A, Shen C, Halperin D et al (2017) Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncology 3:1335\u20131342","journal-title":"JAMA Oncology"},{"key":"1399_CR3","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.2147\/OTT.S182259","volume":"12","author":"JC Yao","year":"2019","unstructured":"Yao JC, Oh DY, Qian J et al (2019) Everolimus for the treatment of advanced gastrointestinal or lung nonfunctional neuroendocrine tumors in East Asian patients: a subgroup analysis of the RADIANT-4 study. Onco Targets Ther 12:1717\u20131728","journal-title":"Onco Targets Ther"},{"key":"1399_CR4","doi-asserted-by":"publisher","first-page":"4656","DOI":"10.1200\/JCO.2009.22.8510","volume":"27","author":"A Rinke","year":"2009","unstructured":"Rinke A, M\u00fcller HH, Schade-Brittinger C et al (2009) Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group. J Clin Oncol 27:4656\u20134663","journal-title":"J Clin Oncol"},{"key":"1399_CR5","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1056\/NEJMoa1316158","volume":"371","author":"ME Caplin","year":"2014","unstructured":"Caplin ME, Pavel M, \u0106wik\u0142a JB et al (2014) Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 371:224\u2013233","journal-title":"N Engl J Med"},{"key":"1399_CR6","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/S0140-6736(15)00817-X","volume":"387","author":"JC Yao","year":"2016","unstructured":"Yao JC, Fazio N, Singh S et al (2016) Everolimus for the treatment of advanced, nonfunctional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet 387:968\u201377","journal-title":"Lancet"},{"key":"1399_CR7","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s00535-014-1006-3","volume":"50","author":"T Aoki","year":"2015","unstructured":"Aoki T, Kokudo N, Komoto I et al (2015) Streptozocin chemotherapy for advanced\/metastatic well-differentiated neuroendocrine tumors: an analysis of a multicenter survey in Japan. J Gastroenterol 50:769\u2013775","journal-title":"J Gastroenterol"},{"key":"1399_CR8","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1093\/jjco\/hyac048","volume":"52","author":"I Komoto","year":"2022","unstructured":"Komoto I, Kokudo N, Aoki T et al (2022) Phase I\/II study of streptozocin monotherapy in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors. Jpn J Clin Oncol 52:716\u2013724","journal-title":"Jpn J Clin Oncol"},{"key":"1399_CR9","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1007\/s00535-021-01827-7","volume":"56","author":"T Ito","year":"2021","unstructured":"Ito T, Masui T, Komoto I et al (2021) JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis. J Gastroenterol 56:1033\u20131044","journal-title":"J Gastroenterol"},{"key":"1399_CR10","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1634\/theoncologist.2017-0364","volume":"23","author":"BN Valdovinos","year":"2018","unstructured":"Valdovinos BN, Bayonas AC, Fonseca PJ et al (2018) Neuroendocrine tumor heterogeneity adds unsertainity to the World Health Organization 2010 classification: real-world data from the Spanish Tumor Registry (R-GETNE). Oncologist 23:422\u2013432","journal-title":"Oncologist"},{"key":"1399_CR11","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.pan.2020.06.002","volume":"20","author":"M Ikeda","year":"2020","unstructured":"Ikeda M, Morizane C, Hijioka S et al (2020) Optimal strategy of systemic treatment for unresectable pancreatic neuroendocrine tumors based upon opinion of Japanese experts. Pancreatology 20:944\u2013950","journal-title":"Pancreatology"},{"key":"1399_CR12","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s10637-017-0466-8","volume":"35","author":"T Ito","year":"2017","unstructured":"Ito T, Honma Y, Hijioka S et al (2017) Phase II study of lanreotide autogel in Japanese patients with unresectable or metastatic well-differentiated neuroendocrine tumors. Invest New Drugs. 35:499\u2013508","journal-title":"Invest New Drugs."},{"key":"1399_CR13","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1159\/000477585","volume":"106","author":"S Singh","year":"2018","unstructured":"Singh S, Carnaghi C, Buzzoni R et al (2018) Everolimus in neuroendoctine tumors of the gastrointestinal tract and unknown primary. Neuroendocrinology 106:211\u2013220","journal-title":"Neuroendocrinology"},{"key":"1399_CR14","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1007\/s00280-018-3656-y","volume":"82","author":"H Shibuya","year":"2018","unstructured":"Shibuya H, Hijioka S, Sakamoto Y et al (2018) Multicenter clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy. Cancer Chemother Pharmacol 82:661\u2013668","journal-title":"Cancer Chemother Pharmacol"},{"key":"1399_CR15","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/j.ejca.2015.04.005","volume":"51","author":"LM Dilz","year":"2015","unstructured":"Dilz LM, Denecke T, Steffen IG et al (2015) Streptozocin\/5-fluorouracil chemotherapy is associated with durable response in patients with advanced pancreatic neuroendocrine tumors. Eur J Cancer 51:1253\u201362","journal-title":"Eur J Cancer"},{"key":"1399_CR16","doi-asserted-by":"crossref","unstructured":"Kunz PL, Catalano PJ, Nimeiri H et al (2018) A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: a trial of the ECOG-ACRIN Cancer Research Group (E2211). J Clin Oncol 36(suppl; abstr 4004)","DOI":"10.1200\/JCO.2018.36.15_suppl.4004"},{"key":"1399_CR17","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ctrv.2016.01.005","volume":"44","author":"A Lamarca","year":"2016","unstructured":"Lamarca A, Elliott E, Barriuso J et al (2016) Chemotherapy for advanced non-pancreatic well-differentiated neuroendocrine tumours of the gastrointestinal tract, a systematic review and meta-analysis: A lost cause? Cancer Treat Rev 44:26\u201341","journal-title":"Cancer Treat Rev"},{"key":"1399_CR18","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1056\/NEJMoa1607427","volume":"376","author":"J Strosberg","year":"2017","unstructured":"Strosberg J, El-Haddad G, Wolin E et al (2017) Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med 376:125\u2013135","journal-title":"N Engl J Med"},{"key":"1399_CR19","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1159\/000443167","volume":"103","author":"M Pavel","year":"2016","unstructured":"Pavel M, O\u2019Toole D, Costa F et al (2016) ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 103:172\u201385","journal-title":"Neuroendocrinology."},{"key":"1399_CR20","unstructured":"National Comprehensive Cancer Network (NCCN) Clinical practice guidelines in oncology for neuroendocrine and adrenal tumors (Version 4.2021). https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/neuroendocrine.pdf"},{"key":"1399_CR21","doi-asserted-by":"crossref","unstructured":"Pavel M, O\u00a8 berg K, Falconi M et al (2020) Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 31:844\u201360","DOI":"10.1016\/j.annonc.2020.03.304"},{"key":"1399_CR22","doi-asserted-by":"publisher","first-page":"17601","DOI":"10.1038\/s41598-022-22718-8","volume":"12","author":"S Yamamoto","year":"2022","unstructured":"Yamamoto S, Sakakibara N, Hirano H et al (2022) The real-world selection of first-line systemic therapy regimen for metastatic gastroenteropancreatic neuroendocrine neoplasm in Japan. Sci Rep 12:17601","journal-title":"Sci Rep"},{"key":"1399_CR23","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1016\/S0140-6736(11)61742-X","volume":"378","author":"ME Pavel","year":"2011","unstructured":"Pavel ME, Hainsworth JD, Baudin E et al (2011) Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2); a randomised, placebo-controlled, phase 3 study. Lancet 378:2005\u20132012","journal-title":"Lancet"},{"key":"1399_CR24","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1634\/theoncologist.2017-0622","volume":"24","author":"J Capdevila","year":"2019","unstructured":"Capdevila J, Teule A, Barriuso J et al (2019) Phase II study of everolimus and octreotide LAR in patients with nonfunctioning gastrointestinal neuroendocrine tumors: The GETNE1003_EVELAR study. Oncologist 24:38\u201346","journal-title":"Oncologist"},{"key":"1399_CR25","doi-asserted-by":"publisher","first-page":"2304","DOI":"10.1200\/JCO.20.03368","volume":"39","author":"J Capdevila","year":"2021","unstructured":"Capdevila J, Fazio N, Lopez C et al (2021) Lenvatinib in patients with advanced Grad 1\/2 pancreatic and gastrointestinal neuroendocrine tumors: results of the phase II TALENT trial (GETNE 1509). J Clin Oncol 39:2304\u20132312","journal-title":"J Clin Oncol"},{"key":"1399_CR26","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1016\/S1470-2045(20)30496-4","volume":"21","author":"J Xu","year":"2020","unstructured":"Xu J, Shen L, Li ZJ et al (2020) Surufatinib in advanced extrapancreatic neuroendocrine tumors (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 21:1500\u201312","journal-title":"Lancet Oncol"},{"key":"1399_CR27","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.ejca.2022.06.024","volume":"172","author":"F Longo-Munoz","year":"2022","unstructured":"Longo-Munoz F, Castellano D, Alexandre J et al (2022) Lurbinectedin in patients with pretreated neuroendocrine tumors: Results from a phase II basket study. Eur J Cancer 172:340\u2013348","journal-title":"Eur J Cancer"},{"key":"1399_CR28","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/j.pan.2020.07.010","volume":"20","author":"R Shimoyama","year":"2020","unstructured":"Shimoyama R, Hijioka S, Mizuno N et al (2020) Study protocol for a multi-institutional randomized phase III study comparing combined everolimus plus lanreotide therapy and everolimus monotherapy in patients with unresectable or recurrent gastroenteropancreatic neuroendocrile tumors; Japan Clinical Oncology Group Study JCOG1901 (STARTER-NET study). Pancreatology 20:1183\u20131188","journal-title":"Pancreatology"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-023-01399-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-023-01399-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-023-01399-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T20:07:35Z","timestamp":1700597255000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-023-01399-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,19]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["1399"],"URL":"https:\/\/doi.org\/10.1007\/s10637-023-01399-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3033156\/v1","asserted-by":"object"}]},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,19]]},"assertion":[{"value":"7 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The patient's data in the case presentation was provided from the multicenter retrospective study approved by the institutional review board of the National Cancer Center (2021-440).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Yoshitaka Honma received honoraria from Novartis Pharma and Teijin Pharma. Masafumi Ikeda received honoraria from AbbVie, AstraZeneca, Chugai, Eisai, Eli Lilly Japan, Fujifilm Toyama Chemical, Guardant Health Japan, Incyte Biosciences Japan, MSD, Nihon Servier, Novartis, Nippon Kayaku, Ono, Taisho Pharmaceutical, Teijin, Takeda, Taiho and Yakult. And research funding (institution) from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Chiome Bioscience, Delta-Fly Pharma, Eisai, Eli Lilly Japan, Invitae, MSD, J-Pharma, Merck biopharma, Merus N.V., Novartis, Nihon Servier, Ono, Pfizer, and Syneos Health. And has consulted for AstraZeneca, Chugai, MSD, Nihon Servier, and Novartis. Susumu Hijioka received honoraria from Novartis Pharma and Teijin Pharma. Shigemi Matsumoto: received honoraria from Novartis Pharma and Taiho Pharmaceutical Co. Ltd. Tetsuhide Ito has no conflict of interest directly relevant to the content of this article. Taku Aoki: has no conflict of interest directly relevant to the content of this article. Junji Furuse received honoraria from Ono Pharma, Chugai Pharma, Eisai, Eli Lilly, Astra Zeneca, Yakult, Servier, MSD, Novartis Pharma, Takeda, Bayer, Taiho Pharma, EA Pharma, Teijin pharma, Daiichi Sankyo, Terumo, Incyte Biosciences, J-Pharma, Fuji film, Astellas, Onco Therapy Science, Delta-Fly-Pharma, Merck Bio. And research funding from Astellas, Astra Zeneca, Incyte Biosciences Japan, Eisai, MSD, Ono Pharmaceutical, Sanofy, J-Pharma, Daiichi Sankyo, Sumitomo Dainippon, Taiho Pharmaceutical, Takeda, Delta-Fly-Pharma, Chugai Pharma","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}