Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 7/2017

17.03.2017 | Original Article – Clinical Oncology

The effect of adjuvant chemotherapy in patients with intrahepatic cholangiocarcinoma: a matched pair analysis

verfasst von: Nora Schweitzer, Tim Weber, Martha M. Kirstein, Mareike Fischer, Anna-Maria Kratzel, Tanja Reineke-Plaaß, Frank Lehner, Michael P. Manns, Arndt Vogel

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The purpose of this study was to identify prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) treated with resection and to investigate the effect of adjuvant chemotherapy (CT).

Methods

Patients with ICC diagnosed between 2000 and 2015 treated at Hannover Medical School were included. Clinicopathologic characteristics were analyzed in univariate and multivariate analysis. In a matched pair survival analysis, patients with or without adjuvant CT were matched by these prognostic factors.

Results

Two hundred and ten patients were included. Median survival was 28.7 months, 1-, 3-, and 5-year survival rates were 72.8%, 29.6%, and 14.1%, respectively. In multivariate analysis, lymph node involvement (p = 0.006, HR 1.84), larger tumor size (p = 0.013, HR 1.79), vascular invasion (p = 0.038, HR 1.70), and prolongation of prothrombin time (p < 0.001, HR 4.20) were significantly related to poor survival. Thirty-nine patients received adjuvant CT of which 60% had lymph node involvement. Each 25 patients with and without adjuvant CT were matched to the identified prognostic factors. The median survival of patients with adjuvant CT was 33.5 months, compared to 18 months in the control group (p = 0.002). The 1-, 3-, and 5-year survival rates were 96, 36, and 12%, compared to 60, 4, and 0% in non-treated patients.

Conclusions

We identified several prognostic factors for patients with ICC treated with resection. Our data support the use of adjuvant CT in patients with ICC. The results of prospective randomized controlled studies will clarify the role of adjuvant CT in the future.
Literatur
Zurück zum Zitat Alvaro D, Crocetti E, Ferretti S, Bragazzi MC, Capocaccia R, AISF Cholangiocarcinoma committee (2010) Descriptive epidemiology of cholangiocarcinoma in Italy. Dig Liver Dis 42(7):490–495CrossRefPubMed Alvaro D, Crocetti E, Ferretti S, Bragazzi MC, Capocaccia R, AISF Cholangiocarcinoma committee (2010) Descriptive epidemiology of cholangiocarcinoma in Italy. Dig Liver Dis 42(7):490–495CrossRefPubMed
Zurück zum Zitat Bektas H, Yeyrek C, Kleine M, Vondran FW, Timrott K, Schweitzer N, Vogel A, Jager MD, Schrem H, Klempnauer J et al (2015) Surgical treatment for intrahepatic cholangiocarcinoma in Europe: a single center experience. J Hepatobiliary Pancreat Sci 22(2):131–137CrossRefPubMed Bektas H, Yeyrek C, Kleine M, Vondran FW, Timrott K, Schweitzer N, Vogel A, Jager MD, Schrem H, Klempnauer J et al (2015) Surgical treatment for intrahepatic cholangiocarcinoma in Europe: a single center experience. J Hepatobiliary Pancreat Sci 22(2):131–137CrossRefPubMed
Zurück zum Zitat de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, Pulitano C, Barroso E, Clary BM, Aldrighetti L et al (2011) Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol 29(23):3140–3145CrossRefPubMed de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, Pulitano C, Barroso E, Clary BM, Aldrighetti L et al (2011) Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol 29(23):3140–3145CrossRefPubMed
Zurück zum Zitat Edeline J, Bonnetain F, Phelip JM, Watelet J, Hammel P, Joly J, Ben Abdelghani M, Rosmorduc O, Bouhier-Leporrier K, Jouve J et al (2017) Gemox versus surveillance following surgery of localized biliary tract cancer: results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. J Clin Oncol 35(suppl 4S; abstract 225) Edeline J, Bonnetain F, Phelip JM, Watelet J, Hammel P, Joly J, Ben Abdelghani M, Rosmorduc O, Bouhier-Leporrier K, Jouve J et al (2017) Gemox versus surveillance following surgery of localized biliary tract cancer: results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. J Clin Oncol 35(suppl 4S; abstract 225)
Zurück zum Zitat Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G, Iacono C (2009) Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg 33(6):1247–1254CrossRefPubMed Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G, Iacono C (2009) Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg 33(6):1247–1254CrossRefPubMed
Zurück zum Zitat Hoehn RS, Wima K, Ertel AE, Meier A, Ahmad SA, Shah SA, Abbott DE (2015) Adjuvant chemotherapy and radiation therapy is associated with improved survival for patients with extrahepatic cholangiocarcinoma. Ann Surg Oncol 22(Suppl 3):S1133–S1139CrossRefPubMed Hoehn RS, Wima K, Ertel AE, Meier A, Ahmad SA, Shah SA, Abbott DE (2015) Adjuvant chemotherapy and radiation therapy is associated with improved survival for patients with extrahepatic cholangiocarcinoma. Ann Surg Oncol 22(Suppl 3):S1133–S1139CrossRefPubMed
Zurück zum Zitat Horgan AM, Amir E, Walter T, Knox JJ (2012) Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol 30(16):1934–1940CrossRefPubMed Horgan AM, Amir E, Walter T, Knox JJ (2012) Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol 30(16):1934–1940CrossRefPubMed
Zurück zum Zitat Howell M, Valle JW (2015) The role of adjuvant chemotherapy and radiotherapy for cholangiocarcinoma. Best Pract Res Clin Gastroenterol 29(2):333–343CrossRefPubMed Howell M, Valle JW (2015) The role of adjuvant chemotherapy and radiotherapy for cholangiocarcinoma. Best Pract Res Clin Gastroenterol 29(2):333–343CrossRefPubMed
Zurück zum Zitat Isa T, Kusano T, Shimoji H, Takeshima Y, Muto Y, Furukawa M (2001) Predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma. Am J Surg 181(6):507–511CrossRefPubMed Isa T, Kusano T, Shimoji H, Takeshima Y, Muto Y, Furukawa M (2001) Predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma. Am J Surg 181(6):507–511CrossRefPubMed
Zurück zum Zitat Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC (2002) Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol 37(6):806–813CrossRefPubMed Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC (2002) Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol 37(6):806–813CrossRefPubMed
Zurück zum Zitat Lang H, Sotiropoulos GC, Sgourakis G, Schmitz KJ, Paul A, Hilgard P, Zopf T, Trarbach T, Malago M, Baba HA et al (2009) Operations for intrahepatic cholangiocarcinoma: single-institution experience of 158 patients. J Am Coll Surg 208(2):218–228CrossRefPubMed Lang H, Sotiropoulos GC, Sgourakis G, Schmitz KJ, Paul A, Hilgard P, Zopf T, Trarbach T, Malago M, Baba HA et al (2009) Operations for intrahepatic cholangiocarcinoma: single-institution experience of 158 patients. J Am Coll Surg 208(2):218–228CrossRefPubMed
Zurück zum Zitat Li T, Qin LX, Zhou J, Sun HC, Qiu SJ, Ye QH, Wang L, Tang ZY, Fan J (2014) Staging, prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection. Liver Int 34(6):953–960CrossRefPubMed Li T, Qin LX, Zhou J, Sun HC, Qiu SJ, Ye QH, Wang L, Tang ZY, Fan J (2014) Staging, prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection. Liver Int 34(6):953–960CrossRefPubMed
Zurück zum Zitat Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. 2014. Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: Systematic review and meta-analysis. JAMA Surg 149(6):565–574CrossRefPubMed Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. 2014. Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: Systematic review and meta-analysis. JAMA Surg 149(6):565–574CrossRefPubMed
Zurück zum Zitat Morimoto Y, Tanaka Y, Ito T, Nakahara M, Nakaba H, Nishida T, Fujikawa M, Ito T, Yamamoto S, Kitagawa T (2003) Long-term survival and prognostic factors in the surgical treatment for intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg 10(6):432–440CrossRefPubMed Morimoto Y, Tanaka Y, Ito T, Nakahara M, Nakaba H, Nishida T, Fujikawa M, Ito T, Yamamoto S, Kitagawa T (2003) Long-term survival and prognostic factors in the surgical treatment for intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg 10(6):432–440CrossRefPubMed
Zurück zum Zitat Nathan H, Pawlik TM, Wolfgang CL, Choti MA, Cameron JL, Schulick RD. 2007. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg 11(11):1488–1496CrossRefPubMed Nathan H, Pawlik TM, Wolfgang CL, Choti MA, Cameron JL, Schulick RD. 2007. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg 11(11):1488–1496CrossRefPubMed
Zurück zum Zitat Ohtsuka M, Ito H, Kimura F, Shimizu H, Togawa A, Yoshidome H, Miyazaki M (2002) Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival. Br J Surg 89(12):1525–1531CrossRefPubMed Ohtsuka M, Ito H, Kimura F, Shimizu H, Togawa A, Yoshidome H, Miyazaki M (2002) Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival. Br J Surg 89(12):1525–1531CrossRefPubMed
Zurück zum Zitat Patel T (2001) Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the united states. Hepatology 33(6):1353–1357CrossRefPubMed Patel T (2001) Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the united states. Hepatology 33(6):1353–1357CrossRefPubMed
Zurück zum Zitat Shaib YH, Davila JA, McGlynn K, El-Serag HB (2004) Rising incidence of intrahepatic cholangiocarcinoma in the united states: a true increase? J Hepatol 40(3):472–477CrossRefPubMed Shaib YH, Davila JA, McGlynn K, El-Serag HB (2004) Rising incidence of intrahepatic cholangiocarcinoma in the united states: a true increase? J Hepatol 40(3):472–477CrossRefPubMed
Zurück zum Zitat Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T, Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract (2002) Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95(8):1685–1695CrossRefPubMed Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T, Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract (2002) Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95(8):1685–1695CrossRefPubMed
Zurück zum Zitat Taylor-Robinson SD, Toledano MB, Arora S, Keegan TJ, Hargreaves S, Beck A, Khan SA, Elliott P, Thomas HC (2001) Increase in mortality rates from intrahepatic cholangiocarcinoma in England and wales 1968–1998. Gut 48(6):816–820CrossRefPubMedPubMedCentral Taylor-Robinson SD, Toledano MB, Arora S, Keegan TJ, Hargreaves S, Beck A, Khan SA, Elliott P, Thomas HC (2001) Increase in mortality rates from intrahepatic cholangiocarcinoma in England and wales 1968–1998. Gut 48(6):816–820CrossRefPubMedPubMedCentral
Zurück zum Zitat Utada M, Ohno Y, Tamaki T, Sobue T, Endo G (2014) Long-term trends in incidence and mortality of intrahepatic and extrahepatic bile duct cancer in Japan. J Epidemiol 24(3):193–199CrossRefPubMed Utada M, Ohno Y, Tamaki T, Sobue T, Endo G (2014) Long-term trends in incidence and mortality of intrahepatic and extrahepatic bile duct cancer in Japan. J Epidemiol 24(3):193–199CrossRefPubMed
Zurück zum Zitat Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP et al (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362(14):1273–1281CrossRefPubMed Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP et al (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362(14):1273–1281CrossRefPubMed
Metadaten
Titel
The effect of adjuvant chemotherapy in patients with intrahepatic cholangiocarcinoma: a matched pair analysis
verfasst von
Nora Schweitzer
Tim Weber
Martha M. Kirstein
Mareike Fischer
Anna-Maria Kratzel
Tanja Reineke-Plaaß
Frank Lehner
Michael P. Manns
Arndt Vogel
Publikationsdatum
17.03.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2017
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-017-2392-8

Weitere Artikel der Ausgabe 7/2017

Journal of Cancer Research and Clinical Oncology 7/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.