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European Radiology

, Volume 27, Issue 2, pp 526–535 | Cite as

Advanced-stage hepatocellular carcinoma with portal vein thrombosis: conventional versus drug-eluting beads transcatheter arterial chemoembolization

  • Boris Gorodetski
  • Julius Chapiro
  • Ruediger Schernthaner
  • Rafael Duran
  • MingDe Lin
  • Howard Lee
  • David Lenis
  • Elizabeth A. Stuart
  • Bareng Aletta Sanny Nonyane
  • Vasily Pekurovsky
  • Anobel Tamrazi
  • Bernhard Gebauer
  • Todd Schlachter
  • Timothy M. Pawlik
  • Jean-Francois Geschwind
Hepatobiliary-Pancreas

Abstract

Objectives

Our study sought to compare the overall survival in patients with hepatocellular carcinoma (HCC) and portal venous thrombosis (PVT), treated with either conventional trans-arterial chemoembolization (cTACE) or drug-eluting beads (DEB) TACE.

Methods

This retrospective analysis included a total of 133 patients, treated without cross-over and compared head-to-head by means or propensity score weighting. Mortality was compared using survival analysis upon propensity score weighting. Adverse events and liver toxicity grade ≥3 were recorded and reported for each TACE. In order to compare with historical sorafenib studies, a sub-group analysis was performed and included patients who fulfilled the SHARP inclusion criteria.

Results

The median overall survival (MOS) of the entire cohort was 4.53 months (95 % CI, 3.63–6.03). MOS was similar across treatment arms, no significant difference between cTACE (N = 95) and DEB-TACE (N = 38) was observed (MOS of 5.0 vs. 3.33 months, respectively; p = 0.157). The most common adverse events after cTACE and DEB- TACE, respectively, were as follows: post-embolization syndrome [N = 57 (30.0 %) and N = 38 (61.3 %)], diarrhea [N = 3 (1.6 %) and N = 3 (4.8 %)], and encephalopathy [N = 11 (5.8 %) and N = 2 (3.2 %)].

Conclusion

Our retrospective study could not reveal a difference in toxicity and efficiency between cTACE and DEB-TACE for treatment of advanced stage HCC with PVT.

Key Points

Conventional TACE (cTACE) and drug-eluting-beads TACE (DEB-TACE) demonstrated equal safety profiles.

Survival rates after TACE are similar to patients treated with sorafenib.

Child-Pugh class and tumor burden are reliable predictors of survival.

Keywords

Liver Hepatocellular carcinoma Chemoembolization Adverse effects Propensity score 

Abbreviations

BCLC

Barcelona Clinic Liver Cancer

CT

Computed tomography

cTACE

Conventional trans-arterial chemoembolization

CTCAE

National Cancer Institute Common Terminology Criteria for Adverse Events

DEB-TACE

Drug-eluting beads TACE

EASL

European Association for the Study of the Liver

ECOG PS

Eastern Cooperative Oncology Group performance status

HCC

Hepatocellular carcinoma

HKLC

Hong Kong Liver Cancer

IAT

Intra-arterial therapy

MOS

Median overall survival

MRI

Magnet resonance imaging

PD

Progressive disease

PES

Post-embolic syndrome

PVT

Portal-venous thrombosis

SD

Stable disease

SHARP

Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol

TACE

Trans-arterial chemoembolization

Y90 RE

Yttrium 90 radioembolization

Notes

Acknowledgments

The scientific guarantor of this publication is Jean-Francois Geschwind MD. The authors of this manuscript declare relationships with the following companies. Jean-Francois Geschwind: Philips Medical, Nordion, Biocompatibles/BTG, Bayer HealthCare, DOB, Context Vision, SIR, RSNA; Guerbet

MingDe Lin: Philips Research North America employee.

Boris Gorodetski, Julius Chapiro, Ruediger Schernthaner, Rafael Duran, Howard Lee, David Lenis, Elizabeth A. Stuart, Bareng Aletta Sanny Nonyane, Vasily Pekurovsky, Anobel Tamrazi, and Timothy M. Pawlik: no relevant relationship to a company.

This study was funded by NIH/NCI R01 CA160771, P30 CA006973, NCRR UL1 RR 025005, Philips Research North America, Briarcliff Manor, New York, Ernst Ludwig Ehrlich Foundation, Gerhard C. Starck Foundation and the Rolf W. Günther Foundation for Radiological Science. There are no financial or other conflicts of interest in relation to this manuscript. David Lenis, Elizabeth A. Stuart PhD and Bareng Aletta Sanny Nonyane PhD kindly provided statistical advice for this manuscript. Institutional Review Board approval was obtained. Written informed consent was waived by the Institutional Review Board. Some study subjects or cohorts have been previously presented at the RSNA conference 2014 and at the CIRSE conference in Lisbon 2015.

Gorodetski, et al. Survival outcomes in patients with advanced-stage HCC and portal vein thrombosis: Comparison between conventional and drug-eluting beads TACE. The abstract was presented at the 100th Scientific Assembly and Annual Meeting of the Radiological Society of North America. Chicago, Illinois, 30 November – 5 December 2014.

Gorodetski, et al. Is trans-arterial chemoembolization safe in patients with advanced to end-stage HCC and portal vein invasion? Comparison between conventional and drug-eluting beads TACE. The abstract was presented at the last CIRSE meeting. Lisbon, Portugal, 26 – 30 September 2015.

Methodology: retrospective, observational, performed at one institution.

Supplementary material

330_2016_4445_MOESM1_ESM.docx (55 kb)
ESM 1 (DOCX 55 kb)

References

  1. 1.
    Forner A, Llovet JM, Bruix J (2012) Hepatocellular carcinoma. Lancet 379:1245–1255CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29CrossRefPubMedGoogle Scholar
  3. 3.
    (2014) Global battle against cancer won't be won with treatment alone--effective prevention measures urgently needed to prevent cancer crisis. Cent Eur J Public Health 22:23, 28Google Scholar
  4. 4.
    Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338CrossRefPubMedGoogle Scholar
  5. 5.
    Schwarz RE, Abou-Alfa GK, Geschwind JF et al (2010) Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus statement. HPB (Oxford) 12:313–320CrossRefGoogle Scholar
  6. 6.
    Bruix J, Sherman M, American Association for the Study of Liver D (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Chapiro J, Tacher V, Geschwind JF (2013) Intraarterial therapies for primary liver cancer: state of the art. Expert Rev Anticancer Ther 13:1157–1167CrossRefPubMedGoogle Scholar
  8. 8.
    Yau T, Tang VY, Yao TJ, Fan ST, Lo CM, Poon RT (2014) Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology 146:1691–1700.e1693CrossRefPubMedGoogle Scholar
  9. 9.
    Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390CrossRefPubMedGoogle Scholar
  10. 10.
    Villanueva A, Hernandez-Gea V, Llovet JM (2013) Medical therapies for hepatocellular carcinoma: a critical view of the evidence. Nat Rev Gastroenterol Hepatol 10:34–42CrossRefPubMedGoogle Scholar
  11. 11.
    Kalva SP, Pectasides M, Liu R et al (2013) Safety and effectiveness of chemoembolization with drug-eluting beads for advanced-stage hepatocellular carcinoma. Cardiovasc Intervent Radiol. doi: 10.1007/s00270-013-0654-7 PubMedGoogle Scholar
  12. 12.
    Prajapati HJ, Dhanasekaran R, El-Rayes BF et al (2013) Safety and efficacy of doxorubicin drug-eluting bead transarterial chemoembolization in patients with advanced hepatocellular carcinoma. J Vasc Interv Radiol 24:307–315CrossRefPubMedGoogle Scholar
  13. 13.
    Georgiades CS, Hong K, D'Angelo M, Geschwind JF (2005) Safety and efficacy of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol 16:1653–1659CrossRefPubMedGoogle Scholar
  14. 14.
    Chung GE, Lee JH, Kim HY et al (2011) Transarterial chemoembolization can be safely performed in patients with hepatocellular carcinoma invading the main portal vein and may improve the overall survival. Radiology 258:627–634CrossRefPubMedGoogle Scholar
  15. 15.
    Chapiro J, Geschwind JF (2014) Hepatocellular carcinoma: have we finally found the ultimate staging system for HCC? Nat Rev Gastroenterol Hepatol 11:334–336CrossRefPubMedGoogle Scholar
  16. 16.
    Lammer J, Malagari K, Vogl T et al (2010) Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 33:41–52CrossRefPubMedGoogle Scholar
  17. 17.
    Reyes DK, Vossen JA, Kamel IR et al (2009) Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J 15:526–532CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yau T, Chan P, Ng KK et al (2009) Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of lung metastasis predicts poor response. Cancer 115:428–436CrossRefPubMedGoogle Scholar
  19. 19.
    Cheng AL, Guan Z, Chen Z et al (2012) Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer 48:1452–1465CrossRefPubMedGoogle Scholar
  20. 20.
    Bruix J, Raoul JL, Sherman M et al (2012) Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 57:821–829CrossRefPubMedGoogle Scholar
  21. 21.
    Edeline J, Crouzet L, Campillo-Gimenez B et al (2015) Selective internal radiation therapy compared with sorafenib for hepatocellular carcinoma with portal vein thrombosis. Eur J Nucl Med Mol Imaging. doi: 10.1007/s00259-015-3210-7 PubMedCentralGoogle Scholar
  22. 22.
    de la Torre M, Buades-Mateu J, de la Rosa PA et al (2016) A comparison of survival in patients with hepatocellular carcinoma and portal vein invasion treated by radioembolization or Sorafenib. Liver Int. doi: 10.1111/liv.13098 PubMedGoogle Scholar
  23. 23.
    Kulik LM, Carr BI, Mulcahy MF et al (2008) Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology 47:71–81CrossRefPubMedGoogle Scholar
  24. 24.
    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 138:52–64CrossRefPubMedGoogle Scholar
  25. 25.
    Hilgard P, Hamami M, Fouly AE et al (2010) Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology 52:1741–1749CrossRefPubMedGoogle Scholar
  26. 26.
    Memon K, Kulik L, Lewandowski RJ et al (2013) Radioembolization for hepatocellular carcinoma with portal vein thrombosis: impact of liver function on systemic treatment options at disease progression. J Hepatol 58:73–80CrossRefPubMedGoogle Scholar
  27. 27.
    Biederman DM, Titano JJ, Tabori NE et al (2016) Outcomes of radioembolization in the treatment of hepatocellular carcinoma with portal vein invasion: resin versus glass microspheres. J Vasc Interv Radiol. doi: 10.1016/j.jvir.2016.01.147 Google Scholar
  28. 28.
    Carr BI, Kondragunta V, Buch SC, Branch RA (2010) Therapeutic equivalence in survival for hepatic arterial chemoembolization and yttrium 90 microsphere treatments in unresectable hepatocellular carcinoma: a two-cohort study. Cancer 116:1305–1314CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lee HS, Kim JS, Choi IJ, Chung JW, Park JH, Kim CY (1997) The safety and efficacy of transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma and main portal vein obstruction. A prospective controlled study. Cancer 79:2087–2094CrossRefPubMedGoogle Scholar
  30. 30.
    Luo J, Guo RP, Lai EC et al (2011) Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study. Ann Surg Oncol 18:413–420CrossRefPubMedGoogle Scholar
  31. 31.
    Niu ZJ, Ma YL, Kang P et al (2012) Transarterial chemoembolization compared with conservative treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus: using a new classification. Med Oncol 29:2992–2997CrossRefPubMedGoogle Scholar
  32. 32.
    Chung JW, Park JH, Han JK, Choi BI, Han MC (1995) Hepatocellular carcinoma and portal vein invasion: results of treatment with transcatheter oily chemoembolization. AJR Am J Roentgenol 165:315–321CrossRefPubMedGoogle Scholar
  33. 33.
    Liu L, Zhang C, Zhao Y et al (2014) Transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis: prognostic factors in a single-center study of 188 patients. Biomed Res Int 2014:194278PubMedPubMedCentralGoogle Scholar
  34. 34.
    Zhu K, Chen J, Lai L et al (2014) Hepatocellular carcinoma with portal vein tumor thrombus: treatment with transarterial chemoembolization combined with sorafenib-A retrospective controlled study. Radiology. doi: 10.1148/radiol.14131946:131946 Google Scholar
  35. 35.
    Huang M, Lin Q, Wang H et al (2016) Survival benefit of chemoembolization plus Iodine125 seed implantation in unresectable hepatitis B-related hepatocellular carcinoma with PVTT: a retrospective matched cohort study. Eur Radiol. doi: 10.1007/s00330-015-4198-x Google Scholar
  36. 36.
    Li XL, Guo WX, Hong XD et al (2016) Efficacy of the treatment of transarterial chemoembolization combined with radiotherapy for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score analysis. Hepatol Res. doi: 10.1111/hepr.12657 Google Scholar
  37. 37.
    McEvoy SH, McCarthy CJ, Lavelle LP et al (2013) Hepatocellular carcinoma: illustrated guide to systematic radiologic diagnosis and staging according to guidelines of the American Association for the Study of Liver Diseases. Radiographics 33:1653–1668CrossRefPubMedGoogle Scholar
  38. 38.
    Therneau T (2014) A package for survival analysis in S, pp R package version 2.37-37Google Scholar
  39. 39.
    Uraki J, Yamakado K, Nakatsuka A, Takeda K (2004) Transcatheter hepatic arterial chemoembolization for hepatocellular carcinoma invading the portal veins: therapeutic effects and prognostic factors. Eur J Radiol 51:12–18CrossRefPubMedGoogle Scholar
  40. 40.
    Sato K, Lewandowski RJ, Bui JT et al (2006) Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization. Cardiovasc Intervent Radiol 29:522–529CrossRefPubMedGoogle Scholar
  41. 41.
    Pellerin O, Lin M, Bhagat N, Shao W, Geschwind JF (2013) Can C-arm cone-beam CT detect a micro-embolic effect after TheraSphere radioembolization of neuroendocrine and carcinoid liver metastasis? Cancer Biother Radiopharm 28:459–465CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    van Malenstein H, Maleux G, Vandecaveye V et al (2011) A randomized phase II study of drug-eluting beads versus transarterial chemoembolization for unresectable hepatocellular carcinoma. Onkologie 34:368–376CrossRefPubMedGoogle Scholar
  43. 43.
    Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug-eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46:474–481CrossRefPubMedGoogle Scholar
  44. 44.
    Wang JH, Changchien CS, Hu TH et al (2008) The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma - survival analysis of 3892 patients. Eur J Cancer 44:1000–1006CrossRefPubMedGoogle Scholar
  45. 45.
    de Baere T, Denys A, Briquet R, Chevallier P, Dufaux J, Roche A (1998) Modification of arterial and portal hemodynamics after injection of iodized oils and different emulsions of iodized oils in the hepatic artery: an experimental study. J Vasc Interv Radiol 9:305–310CrossRefPubMedGoogle Scholar
  46. 46.
    Kan Z, Ivancev K, Lunderquist A (1994) Peribiliary plexa--important pathways for shunting of iodized oil and silicon rubber solution from the hepatic artery to the portal vein. An experimental study in rats. Investig Radiol 29:671–676CrossRefGoogle Scholar
  47. 47.
    Kan Z (1996) Dynamic study of iodized oil in the liver and blood supply to hepatic tumors. An experimental investigation in several animal species. Acta Radiol Suppl 408:1–25PubMedGoogle Scholar
  48. 48.
    Shin SW (2009) The current practice of transarterial chemoembolization for the treatment of hepatocellular carcinoma. Korean J Radiol 10:425–434CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Pinter M, Hucke F, Graziadei I et al (2012) Advanced-stage hepatocellular carcinoma: transarterial chemoembolization versus sorafenib. Radiology 263:590–599CrossRefPubMedGoogle Scholar
  50. 50.
    Ozenne V, Paradis V, Pernot S et al (2010) Tolerance and outcome of patients with unresectable hepatocellular carcinoma treated with sorafenib. Eur J Gastroenterol Hepatol 22:1106–1110CrossRefPubMedGoogle Scholar
  51. 51.
    McDonald RJ, McDonald JS, Kallmes DF, Carter RE (2013) Behind the numbers: propensity score analysis-a primer for the diagnostic radiologist. Radiology 269:640–645CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2016

Authors and Affiliations

  • Boris Gorodetski
    • 1
    • 2
  • Julius Chapiro
    • 1
    • 2
  • Ruediger Schernthaner
    • 1
  • Rafael Duran
    • 1
  • MingDe Lin
    • 1
    • 3
  • Howard Lee
    • 1
  • David Lenis
    • 4
  • Elizabeth A. Stuart
    • 4
  • Bareng Aletta Sanny Nonyane
    • 4
  • Vasily Pekurovsky
    • 1
  • Anobel Tamrazi
    • 1
  • Bernhard Gebauer
    • 2
  • Todd Schlachter
    • 1
    • 6
  • Timothy M. Pawlik
    • 5
  • Jean-Francois Geschwind
    • 1
    • 6
  1. 1.Russel H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional RadiologyThe Johns Hopkins HospitalBaltimoreUSA
  2. 2.Department of Diagnostic and Interventional RadiologyCharité Universitätsmedizin BerlinBerlinGermany
  3. 3.U/S Imaging and Interventions (UII), Philips Research North AmericaBriarcliff ManorUSA
  4. 4.Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  5. 5.Department of SurgeryJohns Hopkins HospitalBaltimoreUSA
  6. 6.Department of Radiology and Biomedical ImagingYale University School of MedicineNew HavenUSA

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