CardioVascular and Interventional Radiology

, Volume 35, Issue 1, pp 105–116

Transarterial Hepatic Yttrium-90 Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: Factors Associated with Prolonged Survival

  • Ralf-T. Hoffmann
  • Philipp M. Paprottka
  • Agnes Schön
  • Fabian Bamberg
  • Alexander Haug
  • Eva-Maria Dürr
  • Barbara Rauch
  • Christoph T. Trumm
  • Tobias F. Jakobs
  • Thomas K. Helmberger
  • Maximilian F. Reiser
  • Frank T. Kolligs
Clinical Investigation

Abstract

Introduction

In unresectable intrahepatic cholangiocarcinoma (ICC), systemic chemotherapy often is viewed as the only option, although efficacy is limited. Radioembolization (RE) using yttrium-90 (90Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in patients with ICC and few data on factors influencing prognosis. The purpose of our retrospective analysis was to establish which factors influenced time-to-progression (TTP) and overall survival (OS).

Methods

Patients with unresectable ICC were treated with 90Y resin-microspheres and assessed at 3-monthly intervals. Radiologic response was evaluated by using Response Criteria in Solid Tumors (RECIST). Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on TTP and OS.

Results

Thirty-four treatments were administered to 33 patients without major complications. By RECIST, 12 patients had a partial response, 17 had stable disease, and 5 had progressive disease after 3 months. The median OS was 22 months posttreatment and 43.7 months postdiagnosis. Median TTP was 9.8 months. Survival and TTP were significantly prolonged in patients with ECOG 0 (vs. ECOG 1 or 2; median OS: 29.4, 10, and 5.1 months; TTP: 17.5, 6.9, and 2.4 months), tumor burden ≤25% (OS: 26.7 vs. 6 months; TTP: 17.5 vs. 2.3 months), or tumor response (PR or SD vs. PD; OS: 35.5, 17.7 vs. 5.7 months; TTP: 31.9, 9.8 vs. 2.5 months), respectively (P < 0.001).

Conclusions

Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response.

Keywords

Radioembolization Yttrium-90 microspheres SIR-Spheres SIRT Intrahepatic cholangiocarcinoma ICC 

References

  1. 1.
    Altaee MY, Johnson PJ, Farrant JM, Williams R (1991) Etiologic and clinical characteristics of peripheral and hilar cholangiocarcinoma. Cancer 68(9):2051–2055PubMedCrossRefGoogle Scholar
  2. 2.
    Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42(5):1208–1236PubMedCrossRefGoogle Scholar
  3. 3.
    Burger I, Hong K, Schulick R et al (2005) Transcatheter arterial chemoembolization in unresectable cholangiocarcinoma: initial experience in a single institution. J Vasc Interv Radiol 16(3):353–361PubMedCrossRefGoogle Scholar
  4. 4.
    Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK (2002) Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 53(4):810–821PubMedCrossRefGoogle Scholar
  5. 5.
    Duffaud F, Therasse P (2000) New guidelines to evaluate the response to treatment in solid tumors. Bull Cancer 87(12):881–886PubMedGoogle Scholar
  6. 6.
    Eckel F, Schmid RM (2007) Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer 96(6):896–902PubMedCrossRefGoogle Scholar
  7. 7.
    Grove MK, Hermann RE, Vogt DP, Broughan TA (1991) Role of radiation after operative palliation in cancer of the proximal bile ducts. Am J Surg 161(4):454–458PubMedCrossRefGoogle Scholar
  8. 8.
    Gusani NJ, Balaa FK, Steel JL et al (2008) Treatment of unresectable cholangiocarcinoma with gemcitabine-based transcatheter arterial chemoembolization (TACE): a single-institution experience. J Gastrointest Surg 12(1):129–137PubMedCrossRefGoogle Scholar
  9. 9.
    Herber S, Otto G, Schneider J et al (2007) Transarterial chemoembolization (TACE) for inoperable intrahepatic cholangiocarcinoma. Cardiovasc Intervent Radiol 30(6):1156–1165PubMedCrossRefGoogle Scholar
  10. 10.
    Hezel AF, Deshpande V, Zhu AX (2010) Genetics of biliary tract cancers and emerging targeted therapies. J Clin Oncol 28(21):3531–3540PubMedCrossRefGoogle Scholar
  11. 11.
    Ibrahim SM, Mulcahy MF, Lewandowski RJ et al (2008) Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer 113(8):2119–2128PubMedCrossRefGoogle Scholar
  12. 12.
    Inarrairaegui M, Thurston KG, Bilbao JI et al (2010) Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol 21(8):1205–1212PubMedCrossRefGoogle Scholar
  13. 13.
    Jakobs TF, Hoffmann RT, Tatsch K, Trumm C, Reiser MF, Helmberger TK (2007) Developments and perspectives in radioablative techniques. Radiologe 47(12):1083–1088PubMedCrossRefGoogle Scholar
  14. 14.
    Jakobs TF, Hoffmann RT, Fischer T et al (2008) Radioembolization in patients with hepatic metastases from breast cancer. J Vasc Interv Radiol 19(5):683–690PubMedCrossRefGoogle Scholar
  15. 15.
    Jakobs TF, Hoffmann RT, Tatsch K, Trumm C, Reiser MF (2008) Therapy response of liver tumors after selective internal radiation therapy. Radiologe 48(9):839–849PubMedCrossRefGoogle Scholar
  16. 16.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59(4):225–249PubMedCrossRefGoogle Scholar
  17. 17.
    Kennedy AS, Salem R (2010) Radioembolization (yttrium-90 microspheres) for primary and metastatic hepatic malignancies. Cancer J 16(2):163–175PubMedCrossRefGoogle Scholar
  18. 18.
    Kennedy AS, Coldwell D, Nutting C et al (2006) Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys 65(2):412–425PubMedCrossRefGoogle Scholar
  19. 19.
    Kennedy A, Nag S, Salem R et al (2007) Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 68(1):13–23PubMedCrossRefGoogle Scholar
  20. 20.
    Kennedy AS, McNeillie P, Dezarn WA et al (2009) Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. Int J Radiat Oncol Biol Phys 74(5):1494–1500PubMedCrossRefGoogle Scholar
  21. 21.
    Kennedy AS, Nutting C, Jakobs T et al (2009) A first report of radioembolization for hepatic metastases from ocular melanoma. Cancer Invest 27(6):682–690PubMedCrossRefGoogle Scholar
  22. 22.
    Oshima S, Takaishi K, Kurokawa E et al (2009) A case of successful management of recurrent intrahepatic cholangiocarcinoma by repeated radiofrequency ablations. Gan To Kagaku Ryoho 36(12):2404–2406PubMedGoogle Scholar
  23. 23.
    Paik KY, Jung JC, Heo JS, Choi SH, Choi DW, Kim YI (2008) What prognostic factors are important for resected intrahepatic cholangiocarcinoma? J Gastroenterol Hepatol 23(5):766–770PubMedCrossRefGoogle Scholar
  24. 24.
    Patel T (2001) Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 33(6):1353–1357PubMedCrossRefGoogle Scholar
  25. 25.
    Salem R, Thurston KG (2006) Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 3: comprehensive literature review and future direction. J Vasc Interv Radiol 17(10):1571–1593PubMedCrossRefGoogle Scholar
  26. 26.
    Salem R, Lewandowski RJ, Mulcahy MF et al (2010) Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 138(1):52–64PubMedCrossRefGoogle Scholar
  27. 27.
    Saxena A, Bester L, Chua TC, Chu FC, Morris DL (2010) Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option. Ann Surg Oncol 17(2):484–491PubMedCrossRefGoogle Scholar
  28. 28.
    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):472–477PubMedCrossRefGoogle Scholar
  29. 29.
    Stintzing S, Hoffmann RT, Heinemann V, Kufeld M, Muacevic A (2010) Frameless single-session robotic radiosurgery of liver metastases in colorectal cancer patients. Eur J Cancer 46(6):1026–1032PubMedCrossRefGoogle Scholar
  30. 30.
    Stintzing S, Hoffmann RT, Heinemann V, Kufeld M, Rentsch M, Muacevic A (2010) Radiosurgery of liver tumors: value of robotic radiosurgical device to treat liver tumors. Ann Surg Oncol 17(11):2877–2883PubMedCrossRefGoogle Scholar
  31. 31.
    Tepel J, Hinz S, Klomp HJ, Kapischke M, Kremer B (2004) Intraoperative radiofrequency ablation (RFA) for irresectable liver malignancies. Eur J Surg Oncol 30(5):551–555PubMedCrossRefGoogle Scholar
  32. 32.
    Valle J, Wasan H, Palmer DH et al (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362(14):1273–1281PubMedCrossRefGoogle Scholar
  33. 33.
    van der Hul RL, Plaisier PW, Lameris JS, Veeze-Kuijpers B, van Blankenstein M, Terpstra OT (1994) Proximal cholangiocarcinoma: a multidisciplinary approach. Eur J Surg 160(4):213–218PubMedGoogle Scholar
  34. 34.
    Vente MA, Wondergem M, van der Tweel I et al (2009) Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis. Eur Radiol 19(4):951–959PubMedCrossRefGoogle Scholar
  35. 35.
    Zgodzinski W, Espat NJ (2005) Radiofrequency ablation for incidentally identified primary intrahepatic cholangiocarcinoma. World J Gastroenterol 11(33):5239–5240PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2011

Authors and Affiliations

  • Ralf-T. Hoffmann
    • 1
    • 5
  • Philipp M. Paprottka
    • 1
    • 5
  • Agnes Schön
    • 3
  • Fabian Bamberg
    • 1
  • Alexander Haug
    • 2
  • Eva-Maria Dürr
    • 3
  • Barbara Rauch
    • 3
  • Christoph T. Trumm
    • 1
  • Tobias F. Jakobs
    • 1
  • Thomas K. Helmberger
    • 4
  • Maximilian F. Reiser
    • 1
  • Frank T. Kolligs
    • 3
  1. 1.Institute of Clinical RadiologyLudwig-Maximilians-UniversityMunichGermany
  2. 2.Department of Nuclear MedicineLudwig-Maximilians-UniversityMunichGermany
  3. 3.Department of Medicine IILudwig-Maximilians-UniversityMunichGermany
  4. 4.Department of Radiology, Interventional Radiology and Nuclear MedicineKlinikum BogenhausenMunichGermany
  5. 5.Institute of Clinical RadiologyUniversity of Munich – Campus GrosshadernMunichGermany

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