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

  • Original Article – Clinical Oncology
  • Published:
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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.

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References

  • 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):490–495

    Article  PubMed  Google Scholar 

  • 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):131–137

    Article  PubMed  Google Scholar 

  • 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):3140–3145

    Article  PubMed  Google Scholar 

  • 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)

  • 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):1247–1254

    Article  PubMed  Google Scholar 

  • 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–S1139

    Article  PubMed  Google Scholar 

  • 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):1934–1940

    Article  PubMed  Google Scholar 

  • Howell M, Valle JW (2015) The role of adjuvant chemotherapy and radiotherapy for cholangiocarcinoma. Best Pract Res Clin Gastroenterol 29(2):333–343

    Article  PubMed  Google Scholar 

  • 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):507–511

    Article  CAS  PubMed  Google Scholar 

  • 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):806–813

    Article  PubMed  Google Scholar 

  • Khan SA, Toledano MB, Taylor-Robinson SD (2008) Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma. HPB 10(2):77–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):218–228

    Article  PubMed  Google Scholar 

  • 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):953–960

    Article  PubMed  Google Scholar 

  • 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):565–574

    Article  PubMed  Google Scholar 

  • 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):432–440

    Article  PubMed  Google Scholar 

  • 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):1488–1496

    Article  PubMed  Google Scholar 

  • 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):1525–1531

    Article  CAS  PubMed  Google Scholar 

  • Patel T (2001) Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the united states. Hepatology 33(6):1353–1357

    Article  CAS  PubMed  Google Scholar 

  • Patel T (2002) Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2:10

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):472–477

    Article  PubMed  Google Scholar 

  • 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):1685–1695

    Article  PubMed  Google Scholar 

  • 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):816–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):193–199

    Article  PubMed  Google Scholar 

  • 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):1273–1281

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was not funded.

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Authors

Corresponding author

Correspondence to Arndt Vogel.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Informed consent

Due to the retrospective nature of this study, a high mortality rate, and the period of interest which was analyzed (2000–2015), it was not feasible to obtain informed consent. This procedure was approved by the local ethics committee.

Additional information

N. Schweitzer and T. Weber have contributed equally to do this work.

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Schweitzer, N., Weber, T., Kirstein, M.M. et al. The effect of adjuvant chemotherapy in patients with intrahepatic cholangiocarcinoma: a matched pair analysis. J Cancer Res Clin Oncol 143, 1347–1355 (2017). https://doi.org/10.1007/s00432-017-2392-8

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  • DOI: https://doi.org/10.1007/s00432-017-2392-8

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