{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:26Z","timestamp":1787022086141,"version":"build-2736575974"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>More than half of patients with bile duct cancer (BDC) develop recurrence even after curative resection. Recurrent BDC has a poor prognosis, and no optimal treatment modality has been established. We therefore analyzed our experience on the survival outcomes of radiation therapy (RT) for recurrent extrahepatic bile duct cancer (EHBDC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed the records of patients with recurrent EHBDC who underwent concurrent chemoradiation therapy (CCRT) or RT alone at our institution between January 2001 and June 2015. Freedom from locoregional progression (FFLP), progression-free survival (PFS), and overall survival (OS) were assessed, and univariate and multivariate analyses were performed to identify the prognostic factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 76 patients were included in the analysis. The median OS was 16 months and the rates of 2-year FFLP, PFS, and OS were 61%, 25%, and 33%, respectively. Among the evaluable patients, the first site of failure was the locoregional area in 16 patients, distant metastasis in 27, and both sites in 8. On univariate analysis, disease-free interval (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.012) and concurrent chemotherapy (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.040) were found as significant prognostic factors for OS. One patient with CCRT developed a grade 3 hematologic toxicity, and two patients experienced late grade 3 toxicities including duodenal ulcer bleeding and obstruction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RT for recurrent EHBDC showed favorable survival and local control with limited treatment-related toxicities. Considering that the most common pattern of failure was distant metastasis, further studies on the optimal scheme of chemotherapy and RT are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0253285","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T13:30:25Z","timestamp":1623850225000},"page":"e0253285","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Radiation therapy for recurrent extrahepatic bile duct cancer"],"prefix":"10.1371","volume":"16","author":[{"given":"Minji","family":"Koh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1088-0174","authenticated-orcid":true,"given":"Jin-hong","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhoon","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5138-3051","authenticated-orcid":true,"given":"Sang Min","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baek-Yeol","family":"Ryoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heung-Moon","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-pyo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Ho","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9002-1195","authenticated-orcid":true,"given":"Jong Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"issue":"4","key":"pone.0253285.ref001","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/00000658-199610000-00005","article-title":"Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors","volume":"224","author":"A Nakeeb","year":"1996","journal-title":"Annals of surgery"},{"issue":"2","key":"pone.0253285.ref002","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000339695","article-title":"Patterns of initial disease recurrence after resection of biliary tract cancer","volume":"83","author":"SJ Jung","year":"2012","journal-title":"Oncology"},{"issue":"6","key":"pone.0253285.ref003","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1007\/s00268-007-9001-y","article-title":"Surgical resection of hilar cholangiocarcinoma: analysis of survival and postoperative complications","volume":"31","author":"S Hasegawa","year":"2007","journal-title":"World journal of surgery"},{"issue":"6","key":"pone.0253285.ref004","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.jamcollsurg.2015.09.005","article-title":"Recurrence Rate and Pattern of Perihilar Cholangiocarcinoma after Curative Intent Resection","volume":"221","author":"B Groot Koerkamp","year":"2015","journal-title":"Journal of the American College of Surgeons"},{"issue":"8","key":"pone.0253285.ref005","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1002\/cncr.11699","article-title":"Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies","volume":"98","author":"WR Jarnagin","year":"2003","journal-title":"Cancer"},{"issue":"1","key":"pone.0253285.ref006","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/SLA.0000000000000827","article-title":"Surgery for Recurrent Biliary Tract Cancer: A Single-center Experience With 74 Consecutive Resections","volume":"262","author":"Y Takahashi","year":"2015","journal-title":"Annals of surgery"},{"issue":"3","key":"pone.0253285.ref007","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4174\/jkss.2011.81.3.187","article-title":"Survival benefits of surgical resection in recurrent cholangiocarcinoma","volume":"81","author":"SC Song","year":"2011","journal-title":"Journal of the Korean Surgical Society"},{"issue":"4","key":"pone.0253285.ref008","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1245\/s10434-014-4146-z","article-title":"Salvage radiation therapy for isolated local recurrence of extrahepatic cholangiocarcinoma after radical surgery: a retrospective study","volume":"22","author":"SW Kim","year":"2015","journal-title":"Ann Surg Oncol"},{"issue":"1080","key":"pone.0253285.ref009","doi-asserted-by":"crossref","first-page":"20170308","DOI":"10.1259\/bjr.20170308","article-title":"Salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer after radical surgery","volume":"90","author":"E Kim","year":"2017","journal-title":"The British journal of radiology"},{"issue":"2","key":"pone.0253285.ref010","first-page":"265","article-title":"Chemoradiotherapy for locally recurrence after primary resection of biliary-pancreatic cancer","volume":"36","author":"K Maemura","year":"2009","journal-title":"Gan to kagaku ryoho Cancer & chemotherapy"},{"issue":"12","key":"pone.0253285.ref011","first-page":"1996","article-title":"Chemoradiotherapy of unresectable and recurrent cholangiocarcinoma","volume":"34","author":"H Horiuchi","year":"2007","journal-title":"Gan to kagaku ryoho Cancer & chemotherapy"},{"issue":"4","key":"pone.0253285.ref012","doi-asserted-by":"crossref","first-page":"345","DOI":"10.5301\/tj.5000666","article-title":"Clinical outcomes of salvage chemoradiotherapy for locally recurrent biliary tract cancer","volume":"103","author":"J Il Yu","year":"2017","journal-title":"Tumori"},{"issue":"14","key":"pone.0253285.ref013","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","article-title":"Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer","volume":"362","author":"J Valle","year":"2010","journal-title":"The New England journal of medicine"},{"issue":"3","key":"pone.0253285.ref014","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/jjco\/hyw182","article-title":"Survival of surgery for recurrent biliary tract cancer: a single-center experience and systematic review of literature","volume":"47","author":"Y Miyazaki","year":"2017","journal-title":"Japanese journal of clinical oncology"},{"issue":"2","key":"pone.0253285.ref015","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/jhbp.2","article-title":"Patients with recurrent biliary tract cancer have a better prognosis than those with unresectable disease: retrospective analysis of a multi-institutional experience with patients of advanced biliary tract cancer who received palliative chemotherapy","volume":"21","author":"K Ikezawa","year":"2014","journal-title":"Journal of hepato-biliary-pancreatic sciences"},{"issue":"3","key":"pone.0253285.ref016","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.ijrobp.2010.06.018","article-title":"Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma","volume":"81","author":"AP Ghafoori","year":"2011","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"2","key":"pone.0253285.ref017","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ijrobp.2005.07.977","article-title":"Chemoradiation and brachytherapy in biliary tract carcinoma: long-term results","volume":"64","author":"F Deodato","year":"2006","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"4","key":"pone.0253285.ref018","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/S0360-3016(02)02845-6","article-title":"Limitations of conventional doses of chemoradiation for unresectable biliary cancer","volume":"53","author":"CH Crane","year":"2002","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"3","key":"pone.0253285.ref019","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1200\/JCO.2015.61.3778","article-title":"Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis","volume":"34","author":"R Tao","year":"2016","journal-title":"J Clin Oncol."},{"issue":"10","key":"pone.0253285.ref020","doi-asserted-by":"crossref","first-page":"4880","DOI":"10.1002\/cam4.1734","article-title":"Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma","volume":"7","author":"D Elganainy","year":"2018","journal-title":"Cancer medicine"},{"issue":"1","key":"pone.0253285.ref021","doi-asserted-by":"crossref","first-page":"10","DOI":"10.21037\/cco.2019.12.05","article-title":"Radiation dose escalation for locally advanced unresectable intrahepatic and extrahepatic cholangiocarcinoma","volume":"9","author":"S Avila","year":"2020","journal-title":"Chinese clinical oncology"},{"issue":"1","key":"pone.0253285.ref022","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/cam4.975","article-title":"Does radiotherapy still have a role in unresected biliary tract cancer?","volume":"6","author":"EL Pollom","year":"2017","journal-title":"Cancer medicine"},{"issue":"2","key":"pone.0253285.ref023","first-page":"737","article-title":"Radiochemotherapy with Gemcitabine in Unresectable Extrahepatic Cholangiocarcinoma: Long-term Results of a Phase II Study","volume":"36","author":"R Autorino","year":"2016","journal-title":"Anticancer research"},{"key":"pone.0253285.ref024","unstructured":"National Comprehensive Cancer Network (NCCN) Guidelines. https:\/\/www.nccn.org (2020). Accessed 22 Oct 2020."},{"issue":"5","key":"pone.0253285.ref025","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.hpb.2016.12.014","article-title":"Risk stratification and prognostic nomogram for post-recurrence overall survival in patients with recurrent extrahepatic cholangiocarcinoma","volume":"19","author":"BH Kim","year":"2017","journal-title":"HPB: the official journal of the International Hepato Pancreato Biliary Association"},{"issue":"1","key":"pone.0253285.ref026","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1001\/jamasurg.2016.3466","article-title":"Association of Histopathologic Phenotype of Periampullary Adenocarcinomas With Survival","volume":"152","author":"JL Williams","year":"2017","journal-title":"JAMA surgery"},{"issue":"4","key":"pone.0253285.ref027","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.ijrobp.2015.12.003","article-title":"Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation","volume":"94","author":"S Krishnan","year":"2016","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"pone.0253285.ref028","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1200\/JCO.2015.64.2710","article-title":"Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma","volume":"34","author":"TS Hong","year":"2016","journal-title":"J Clin Oncol."},{"issue":"3","key":"pone.0253285.ref029","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.ijrobp.2009.12.031","article-title":"Postoperative chemoradiotherapy for extrahepatic bile duct cancer","volume":"79","author":"JH Park","year":"2011","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"6","key":"pone.0253285.ref030","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1001\/jamaoncol.2019.0270","article-title":"Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial","volume":"5","author":"RT Shroff","year":"2019","journal-title":"JAMA oncology"},{"issue":"7","key":"pone.0253285.ref031","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1001\/jamaoncol.2019.0892","article-title":"Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase 2 Clinical Trial","volume":"5","author":"JE Murphy","year":"2019","journal-title":"JAMA oncology."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253285","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T13:30:55Z","timestamp":1623850255000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253285"}},"subtitle":[],"editor":[{"given":"Randall J.","family":"Kimple","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,16]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0253285","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,16]]}}}