Abstract
Treatment methods for intrahepatic cholangiocarcinoma (ICC) have improved, but their impact on outcome remains unclear. We evaluated the outcomes of patients definitively treated with resection, radiation, and chemotherapy for ICC, stratified by era. Clinico-pathologic characteristics, cause of death, disease-specific survival (DSS), and intrahepatic progression-free survival (IPFS) were compared among patients who underwent resection, radiation, or chemotherapy as definitive treatment strategies for ICC (without distant organ metastasis) between 1997 and 2015. Variables were also analyzed by era (1997-2006 [early] or 2007-2015 [late]) within each group. Among 362 patients in our cohort, 122 underwent resection (early, 38; late, 84), 85 underwent radiation (early, 17; late, 68), and 148 underwent systemic chemotherapy alone (early, 51; late, 97) as definitive treatment strategies, and 7 patients received best supportive care. In the resection group, the 3-year DSS rate was 58% for the early era and 67% for the late era (P = .036), and the 1-year IPFS was 50% for the early era and 75% for the late era (P = .048). In the radiation group, the 3-year DSS was 12% for the early era and 37% for the late era (P = .048), and the 1-year IPFS was 48% for the early era and 64% for the late era (P = .030). In the chemotherapy group, DSS and IPFS did not differ by era. Patients treated with chemotherapy developed liver failure at the time of death significantly more frequently than patients treated with resection (P < .001) or radiation (P < .001). Multivariable analysis identified local therapy (resection or radiation) as a sole predictor of death without liver failure. Survival outcomes have improved for local therapy-based definitive treatment strategies for ICC, which may be attributable to maintaining control of intrahepatic disease, thereby reducing the occurrence of death due to liver failure. Cancer 2017;123:1354-1362. © 2016 American Cancer Society.
Keywords
chemotherapy
intrahepatic cholangiocarcinoma
intrahepatic progression-free survival
local therapy
radiation
resection
MeSH Terms
Adult
Aged
Aged, 80 and over
Cause of Death
Cholangiocarcinoma/complications,diagnosis,mortality,therapy
Combined Modality Therapy/adverse effects,methods
Female
Hepatectomy
Humans
Liver Failure/etiology
Male
Middle Aged
Neoplasm Staging
Odds Ratio
Prognosis
Survival Analysis
Treatment Outcome
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Yamashita Suguru
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Koay Eugene Jon
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Passot Guillaume
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shroff Rachna
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Raghav Kanwal P
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Conrad Claudius
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Chun Yun Shin
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Aloia Thomas A
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Tao Randa
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Kaseb Ahmed
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Javle Milind
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Crane Christopher H
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Vauthey Jean-Nicolas
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
References (32)
32 references, click to expand
-
Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer.
N Engl J Med. 2010 Apr 8;362(14):1273-81
PMID: 20375404
-
Prognostic Impact of Tumor Growth Type on 7th AJCC Staging System for Intrahepatic Cholangiocarcinoma: a Single-Center Experience of 659 Cases.
J Gastrointest Surg. 2015 Jul;19(7):1291-304
PMID: 25820487
-
Significant Improvement in Outcomes of Patients with Intrahepatic Cholangiocarcinoma after Surgery.
World J Surg. 2016 Sep;40(9):2229-36
PMID: 27255940
-
Causes of death in patients with hepatitis B: a natural history cohort study in the United States.
Hepatology. 2013 Jul;58(1):21-30
PMID: 23080403
-
Limitations of conventionally derived chronic liver disease mortality rates: Results of a comprehensive assessment.
Hepatology. 2008 Apr;47(4):1150-7
PMID: 18264998
-
Surgical Approach for Long-term Survival of Patients With Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 434 Patients.
Arch Surg. 2012 Dec;147(12):1107-13
PMID: 22910846
-
Conditional Probability of Long-term Survival After Liver Resection for Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 535 Patients.
JAMA Surg. 2015 Jun;150(6):538-45
PMID: 25831462
-
The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection: association of lymph node metastasis and lymph node dissection with survival.
Ann Surg Oncol. 2009 Nov;16(11):3048-56
PMID: 19626372
-
Rebleeding prophylaxis improves outcomes in patients with hepatocellular carcinoma. A multicenter case-control study.
Hepatology. 2013 Dec;58(6):2079-88
PMID: 23908019
-
Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.
J Clin Oncol. 2016 Feb 10;34(5):460-8
PMID: 26668346
-
Solutions that enable ablative radiotherapy for large liver tumors: Fractionated dose painting, simultaneous integrated protection, motion management, and computed tomography image guidance.
Cancer. 2016 Jul 1;122(13):1974-86
PMID: 26950735
-
Intra-hepatic cholangiocarcinoma--frequency and demographic patterns: thirty-year data from the M.D. Anderson Cancer Center.
J Cancer Res Clin Oncol. 2011 Jul;137(7):1071-8
PMID: 21207060
-
Targeted therapy of advanced gallbladder cancer and cholangiocarcinoma with aggressive biology: eliciting early response signals from phase 1 trials.
Oncotarget. 2013 Jan;4(1):156-65
PMID: 23391555
-
SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma.
J Clin Oncol. 2015 Aug 20;33(24):2617-22
PMID: 25964250
-
Radiation therapy is associated with improved survival in the adjuvant and definitive treatment of intrahepatic cholangiocarcinoma.
Int J Radiat Oncol Biol Phys. 2008 Dec 1;72(5):1495-501
PMID: 18472359
-
Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis.
J Clin Oncol. 2012 Jun 1;30(16):1934-40
PMID: 22529261
-
HER2/neu-directed therapy for biliary tract cancer.
J Hematol Oncol. 2015 May 29;8:58
PMID: 26022204
-
Outcomes following resection of intrahepatic cholangiocarcinoma.
HPB (Oxford). 2015 Apr;17(4):344-51
PMID: 25395176
-
Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis.
J Clin Oncol. 2016 Jan 20;34(3):219-26
PMID: 26503201
-
Safety and efficacy of portal vein embolization before planned major or extended hepatectomy: an institutional experience of 358 patients.
J Gastrointest Surg. 2014 Jan;18(1):45-51
PMID: 24129824
-
Two-surgeon technique for hepatic parenchymal transection of the noncirrhotic liver using saline-linked cautery and ultrasonic dissection.
Ann Surg. 2005 Aug;242(2):172-7
PMID: 16041206
-
Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?
J Hepatol. 2004 Mar;40(3):472-7
PMID: 15123362
-
Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma.
Hepatology. 2014 Apr;59(4):1427-34
PMID: 24122810
-
Capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective single-center study.
Chemotherapy. 2012;58(3):225-32
PMID: 22831988
-
Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection.
Ann Surg. 2008 Jul;248(1):84-96
PMID: 18580211
-
Multimodality treatment of intrahepatic cholangiocarcinoma: A review.
J Surg Oncol. 2016 Jan;113(1):62-83
PMID: 26797780
-
Cholangiocarcinoma.
Lancet. 2005 Oct 8;366(9493):1303-14
PMID: 16214602
-
AJCC 7th edition of TNM staging accurately discriminates outcomes of patients with resectable intrahepatic cholangiocarcinoma: By the AFC-IHCC-2009 study group.
Cancer. 2011 May 15;117(10):2170-7
PMID: 21523730
-
Two-surgeon technique of parenchymal transection contributes to reduced transfusion rate in patients undergoing major hepatectomy: analysis of 1,557 consecutive liver resections.
Surgery. 2010 Jan;147(1):40-8
PMID: 19733879
-
Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment.
Hepatology. 2008 Jul;48(1):308-21
PMID: 18536057
-
Intrahepatic cholangiocarcinoma: new insights in pathology.
Semin Liver Dis. 2011 Feb;31(1):49-60
PMID: 21344350
-
Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study.
Ann Surg Oncol. 2013 Jan;20(1):318-24
PMID: 23149849