{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T11:28:10Z","timestamp":1750505290909,"version":"3.40.5"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Gastroent Surgery"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Neoadjuvant chemoradiotherapy may improve survival in patients with advanced cholangiocarcinoma. This Phase I study aimed to determine the recommended dose of neoadjuvant chemoradiotherapy and decide whether to move to a Phase II study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients diagnosed with resectable stage II\u2013IVa cholangiocarcinoma were administered cisplatin (40 [level 0], 50 [level 1 as starting dose], or 60 [level 2] mg\/m<jats:sup>2<\/jats:sup>), 80\u2009mg\/m<jats:sup>2<\/jats:sup> of S\u20101, and 50.4\u2009Gy of external beam radiation. The recommended dose was defined as a dose one\u2010step lower than the maximum\u2010tolerated dose, which was defined when dose\u2010limiting toxicity was observed in three or more of the six patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve patients were eligible from November 2012 to May 2016. Ten patients had perihilar cholangiocarcinoma and two patients had distal cholangiocarcinoma. Dose\u2010limiting toxicity was observed in one of the first six patients at level 1 and two of the next six patients at level 2; thus, the maximum\u2010tolerated dose was not determined even at level 2 and the recommended dose was determined as level 2. Four patients had partial response, four patients had stable disease, and two patients had progression of disease because of liver metastases. Finally, nine patients underwent radical surgery and seven cases achieved R0 resection. However, five cases suffered biliary leakage and one suffered intrahospital death due to rupture of the hepatic artery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We determined the recommended dose of neoadjuvant chemoradiotherapy for resectable cholangiocarcinoma. However, we terminated the trial due to a high incidence of morbidity and unexpected mortality.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ags3.12682","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T15:52:12Z","timestamp":1682351532000},"page":"808-818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phase I study of neoadjuvant S\u20101 plus cisplatin with concurrent radiation for biliary tract cancer (Tokyo Study Group for Biliary Cancer: TOSBIC02)"],"prefix":"10.1002","volume":"7","author":[{"given":"Yuta","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Surgery Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Itano","sequence":"additional","affiliation":[{"name":"Department of Surgery Keio University School of Medicine  Tokyo Japan"},{"name":"Department of 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