title: Selective internal radiotherapy (SIRT) versus transarterial chemoembolization (TACE) for the treatment of intrahepatic cholangiocellular carcinoma (CCC): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Cholangiocellular carcinoma is the second most common primary liver cancer after hepatocellular carcinoma. Over the last 30 years, the incidence of intrahepatic cholangiocellular carcinoma has risen continuously worldwide. Meanwhile, the intrahepatic cholangiocellular carcinoma has become more common than the extrahepatic growth type and currently accounts for 10-15% of all primary hepatic malignancies. Intrahepatic cholangiocellular carcinoma is typically diagnosed in advanced stages due to late clinical symptoms and an absence of classic risk factors. A late diagnosis precludes curative surgical resection. There is evidence that transarterial chemoembolization leads to better local tumor control and prolongs survival compared to systemic chemotherapy. New data indicates that selective internal radiotherapy, also referred to as radioembolization, provides promising results for treating intrahepatic cholangiocellular carcinoma.
  
  
  METHODS
  This pilot study is a randomized, controlled, single center, phase II trial. Twenty-four patients with intrahepatic cholangiocellular carcinoma will be randomized in a 1:1 ratio to receive either chemoembolization or radioembolization. Randomization will be stratified according to tumor load. Progression-free survival is the primary endpoint; overall survival and time to progression are secondary endpoints. To evaluate treatment success, patients will receive contrast enhanced magnetic resonance imaging every 3 months.
  
  
  CONCLUSIONS
  Currently, chemoembolization is routinely performed in many centers instead of systemic chemotherapy for treating intrahepatic cholangiocellular carcinoma confined to the liver. Recently, radioembolization has been increasingly applied to cholangiocellular carcinoma as second line therapy after TACE failure or even as an alternative first line therapy. Nonetheless, no randomized studies have compared radioembolization and chemoembolization. Considering all this background information, we recognized a strong need for a randomized controlled trial (RCT) to compare the two treatments. Therefore, the present protocol describes the design of a RCT that compares SIRT and TACE as the first line therapy for inoperable CCC confined to the liver.
  
  
  BACKGROUND
  ClinicalTrials.gov, Identifier: NCT01798147, registered 16th of February 2013.
authors.affiliation: Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Center, Langenbeckstr, 1, 55131 Mainz, Germany. roman.kloeckner@unimedizin-mainz.de.
authors.forename: Roman
authors.initials: R
authors.lastname: Kloeckner
authors.forename: Christian
authors.initials: C
authors.lastname: Ruckes
authors.forename: Kai
authors.initials: K
authors.lastname: Kronfeld
authors.forename: Marcus Alexander
authors.initials: MA
authors.lastname: Wörns
authors.forename: Arndt
authors.initials: A
authors.lastname: Weinmann
authors.forename: Peter Robert
authors.initials: PR
authors.lastname: Galle
authors.forename: Hauke
authors.initials: H
authors.lastname: Lang
authors.forename: Gerd
authors.initials: G
authors.lastname: Otto
authors.forename: Waltraud
authors.initials: W
authors.lastname: Eichhorn
authors.forename: Mathias
authors.initials: M
authors.lastname: Schreckenberger
authors.forename: Christoph
authors.initials: C
authors.lastname: Dueber
authors.forename: Michael Bernhard
authors.initials: MB
authors.lastname: Pitton
mesh_terms: D001650:Bile Duct Neoplasms / Q000628:therapy*; D001653:Bile Ducts, Intrahepatic; D016461:Chemoembolization, Therapeutic; D018281:Cholangiocarcinoma / Q000628:therapy*; D002985:Clinical Protocols; D006801:Humans; D017063:Outcome Assessment, Health Care; D012107:Research Design
references.citation: Oncology. 2004;66(3):167-79
references.pmid: 15218306
references.citation: Cardiovasc Intervent Radiol. 2007 Jan-Feb;30(1):6-25
references.pmid: 17103105
references.citation: Hepatology. 2001 Jun;33(6):1353-7
references.pmid: 11391522
references.citation: J Vasc Interv Radiol. 2005 Mar;16(3):353-61
references.pmid: 15758131
references.citation: Gastroenterology. 1991 Jun;100(6):1710-7
references.pmid: 1850376
references.citation: World J Surg. 1995 Jul-Aug;19(4):637-41
references.pmid: 7676713
references.citation: Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1494-500
references.pmid: 19157721
references.citation: N Engl J Med. 2010 Apr 8;362(14):1273-81
references.pmid: 20375404
references.citation: Ann Surg. 1994 Nov;220(5):644-52
references.pmid: 7979612
references.citation: Abdom Imaging. 2004 Sep-Oct;29(5):548-57
references.pmid: 15185025
references.citation: J Comput Assist Tomogr. 1999 Sep-Oct;23(5):670-7
references.pmid: 10524843
references.citation: World J Gastroenterol. 2005 Sep 7;11(33):5239-40
references.pmid: 16127762
references.citation: Ann Surg. 1996 Oct;224(4):463-73; discussion 473-5
references.pmid: 8857851
references.citation: J Hepatobiliary Pancreat Surg. 1999;6(2):117-21
references.pmid: 10398897
references.citation: Ann Surg. 2007 May;245(5):755-62
references.pmid: 17457168
references.citation: J Hepatobiliary Pancreat Surg. 2003;10(4):259-64
references.pmid: 14598144
references.citation: Eur J Radiol. 2012 Dec;81(12):3857-61
references.pmid: 22840383
references.citation: Eur J Gastroenterol Hepatol. 2012 Apr;24(4):437-43
references.pmid: 22261548
references.citation: Br J Surg. 1995 Mar;82(3):382-5
references.pmid: 7796017
references.citation: Surgery. 2000 May;127(5):498-505
references.pmid: 10819057
references.citation: J Clin Oncol. 2005 Jul 20;23(21):4742-54
references.pmid: 16034050
references.citation: Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1552-63
references.pmid: 15590187
references.citation: Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):13-23
references.pmid: 17448867
references.citation: Gastroenterology. 2005 Mar;128(3):620-6
references.pmid: 15765398
references.citation: Clin Radiol. 2011 Apr;66(4):322-8
references.pmid: 21356394
references.citation: Oncologist. 2006 Sep;11(8):913-22
references.pmid: 16951395
references.citation: Cardiovasc Intervent Radiol. 2007 Nov-Dec;30(6):1156-65
references.pmid: 17508242
references.citation: Cardiovasc Intervent Radiol. 2008 May-Jun;31(3):468-76
references.pmid: 18228095
references.citation: Int J Cancer. 2012 Aug 1;131(3):733-40
references.pmid: 21976289
references.citation: Cancer Causes Control. 2001 Dec;12(10):959-64
references.pmid: 11808716
references.citation: Radiographics. 1999 Sep-Oct;19(5):1199-218
references.pmid: 10489176
references.citation: Ann Surg. 2005 Jan;241(1):134-43
references.pmid: 15622001
references.citation: Br J Cancer. 2009 Jun 2;100(11):1765-70
references.pmid: 19436294
references.citation: AJR Am J Roentgenol. 2000 Sep;175(3):721-5
references.pmid: 10954456
references.citation: World J Gastroenterol. 2002 Oct;8(5):943-6
references.pmid: 12378647
references.citation: Hepatology. 1998 Oct;28(4):921-5
references.pmid: 9755226
references.citation: Semin Liver Dis. 2010 Feb;30(1):52-60
references.pmid: 20175033
references.citation: J Vasc Interv Radiol. 2011 Nov;22(11):1545-52
references.pmid: 21849247
references.citation: Cardiovasc Intervent Radiol. 2008 Sep-Oct;31(5):883-8
references.pmid: 18478290
references.citation: Lancet. 2005 Oct 8;366(9493):1303-14
references.pmid: 16214602
references.citation: Eur J Gastroenterol Hepatol. 2002 Sep;14(9):1025-7
references.pmid: 12352225
references.citation: Semin Liver Dis. 2004 May;24(2):155-64
references.pmid: 15192788
references.citation: J Hepatol. 2002 Mar;36(3):321-7
references.pmid: 11867174
references.citation: Cancer. 1993 Apr 15;71(8):2461-5
references.pmid: 8384069
references.citation: Ann Surg. 1998 Jan;227(1):70-9
references.pmid: 9445113
references.citation: Radiology. 1996 Mar;198(3):869-73
references.pmid: 8628885
references.citation: World J Surg. 2005 Jul;29(7):894-8
references.pmid: 15951931
references.citation: Clin Gastroenterol Hepatol. 2007 Sep;5(9):1100-8
references.pmid: 17627902
references.citation: Clin Gastroenterol Hepatol. 2013 Oct;11(10):1358-1365.e1
references.pmid: 23644386
references.citation: J Gastroenterol. 2006 Sep;41(9):893-900
references.pmid: 17048054
references.citation: World J Surg. 2001 Jul;25(7):865-9
references.pmid: 11572025
references.citation: Semin Liver Dis. 2004 May;24(2):115-25
references.pmid: 15192785
references.citation: J Vasc Interv Radiol. 2009 Sep;20(9):1121-30; quiz 1131
references.pmid: 19640737
references.citation: N Engl J Med. 1997 Jun 26;336(26):1889-94
references.pmid: 9197218
references.citation: Cancer Sci. 2004 Jul;95(7):592-5
references.pmid: 15245596
references.citation: Cardiovasc Intervent Radiol. 2010 Feb;33(1):41-52
references.pmid: 19908093
references.citation: Gut. 2001 Jun;48(6):816-20
references.pmid: 11358902
references.citation: AJR Am J Roentgenol. 1998 Jun;170(6):1491-5
references.pmid: 9609160
references.citation: Ann Surg. 2001 Oct;234(4):507-17; discussion 517-9
references.pmid: 11573044
references.citation: Cardiovasc Intervent Radiol. 2012 Feb;35(1):105-16
references.pmid: 21431970