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Chemoembolization Decreases Drop-Off Risk of Hepatocellular Carcinoma Patients on the Liver Transplant List

CardioVascular and Interventional Radiology volume 34, pages 1254–1261 (2011)Cite this article

Abstract

Introduction

The drop-off risk for patients awaiting liver transplantation for hepatocellular carcinoma (HCC) is 22%. Transplant liver availability is expected to worsen, resulting in longer waiting times and increased drop-off rates. Our aim was to determine whether chemoembolization can decrease this risk.

Patients and Methods

Eighty-seven consecutive HCC patients listed for liver transplant (Milan criteria) underwent statistical comparability adjustments using the propensity score (Wilcoxon, Fisher’s, and chi-square tests). Forty-three nonchemoembolization patients and 22 chemoembolization patients were comparable for Child-Pugh and Model for End-Stage Liver Disease scores, tumor size and number, alpha fetoprotein (AFP) levels, and cause of cirrhosis. We calculated the risk of dropping off the transplant list by assigning a transplant time to those who dropped off (equal probability with patients who were on the list longer than the patient in question). The significance level was obtained by calculating the simulation distribution of the difference compared with the permutations of chemoembolization versus nonchemoembolization assignment of the patients. Kaplan–Meier estimators (log-rank test) were used to determine survival rates.

Results

Median follow-up was 187 ± 110 weeks (range 38 to 435, date of diagnosis). The chemoembolization group had an 80% drop-off risk decrease (15% nonchemoembolization versus 3% chemoembolization, p = 0.04). Although survival was better for the chemoembolization group, it did not reach statistical significance. Two-year survival for the nonchemoembolization and chemoembolization group was 57.3% ± 7.1% and 76.0% ± 7.9%, respectively (p = 0.078).

Conclusions

Chemoembolization appears to result in a significant decrease in the risk of dropping off liver transplant list for patients with HCC and results in a tendency toward longer survival.

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References

  1. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699

    Article  PubMed  CAS  Google Scholar 

  2. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A et al (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33:1394–1403

    Article  PubMed  CAS  Google Scholar 

  3. Pelletier SJ, Fu S, Thyagarajan V, Romero-Marrero C, Batheja MJ, Punch JD et al (2009) An intention-to-treat analysis of liver transplantation for hepatocellular carcinoma using organ procurement transplant network data. Liver Transpl 15(8):859–868

    Article  PubMed  Google Scholar 

  4. Stockland AH, Walser EM, Paz-Fumagalli R, McKinney JM, Mayrger GR (2007) Preoperative chemoembolization in patients with hepatocellular carcinoma undergoing liver transplantation: influence of emergent versus elective procedures on patient survival and tumor recurrence rate. Cardiovasc Intervent Radiol 30:888–893

    Article  PubMed  CAS  Google Scholar 

  5. Obed A, Beham A, Püllmann K, Becker H, Schlitt HJ, Lorf T (2007) Patients without hepatocellular carcinoma progression after transarterial chemoembolization benefit from liver transplantation. World J Gastroenterol 13(5):761–767

    PubMed  Google Scholar 

  6. Kim DY, Moon-Choi S, Lee JH, Koh KC, Paik SW, Yoo BC et al (2006) Milan criteria are useful predictors for favorable outcomes in hepatocellular carcinoma patients undergoing liver transplantation after transarterial chemoembolization. World J Gastroenterol 12(43):6992–6997

    Google Scholar 

  7. Wiesner R, Freeman RB, Mulligan DC (2004) Liver transplantation for hepatocellular cancer: the impact of the MELD allocation policy. Gastroenterology 127(Suppl):S261–S267

    Article  PubMed  Google Scholar 

  8. Chapman WC, Majella-Doyle MB, Stuart JE, Vachharajani N, Crippin JS, Anderson CD et al (2008) Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation. Ann Surg 248(4):617–625

    PubMed  Google Scholar 

  9. Dharancy S, Boitard J, Decaens T, Sergent G, Boleslawski E, Duvoux C et al. (2007) Comparison of two techniques of transarterial chemoembolization before liver transplantation for hepatocellular carcinoma: a case–control study. Liver Transplant 13:665–671

    Google Scholar 

  10. Millonig G, Graziadei IW, Freund MC, Jaschke W, Stadlmann S, Ladurner R et al (2007) Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma. Liver Transplant 13:272–279

    Article  Google Scholar 

  11. Bharat A, Brown DB, Crippin JS, Gould JE, Lowell JA, Shenoy S et al (2006) Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve long-term survival. J Am Coll Surg 203:411–420

    Article  PubMed  Google Scholar 

  12. http://optn.transplant.hrsa.gov/latestData/rptData.asp. Accessed 1 Nov 2010

  13. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35(5):1164–1171

    Article  PubMed  CAS  Google Scholar 

  14. Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37(2):429–442

    Article  PubMed  CAS  Google Scholar 

  15. Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F et al (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224(1):47–54

    Article  PubMed  Google Scholar 

  16. Graziadei IW, Sandmueller H, Waldenberger P, Koenigsrainer A, Nachbaur K, Jaschke W et al (2003) Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transplant 9(6):557–563

    Article  Google Scholar 

  17. Otto G, Herber S, Heise M, Lohse AW, Monch C, Bittinger F et al (2006) Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transplant 12:1260–1267

    Article  Google Scholar 

  18. Sotiropoulos GC, Malago M, Molmenti EP, Radtke A, Brokalaki EI, Nadalin S et al (2005) Disease course after liver transplantation for hepatocellular carcinoma in patients with complete tumor necrosis in liver explants after performance of bridging treatments. Eur J Med Res 10(12):539–542

    PubMed  Google Scholar 

  19. Saborido BP, Meneu JC, Moreno E, García I, Moreno A, Fundora Y (2005) Is transarterial chemoembolization necessary before liver transplantation for hepatocellular carcinoma? Am J Surg 190:383–387

    Article  Google Scholar 

  20. Decaens T, Roudot-Thoraval F, Bresson-Hadni S, Meyer C, Gugenheim J, Durand F et al (2005) Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transplant 11:767–775

    Article  Google Scholar 

  21. Otto G, Heise M, Moench C, Herber S, Bittinger F, Schuchmann M et al (2007) Transarterial chemoembolization before liver transplantation in 60 patients with hepatocellular carcinoma. Transplant Proc 39:537–539

    Article  PubMed  CAS  Google Scholar 

  22. Zimmerman MA, Trotter JF, Wachs M, Bak T, Campsen J, Wright F et al (2007) Predictors of long-term outcome following liver transplantation for hepatocellular carcinoma: a single-center experience. Transplant Int 20(9):747–753

    Article  Google Scholar 

  23. Aloia TA, Adam R, Samuel D, Azoulay D, Castaing DA (2007) Decision analysis model identifies the interval of efficacy for transarterial chemoembolization (TACE) in cirrhotic patients with hepatocellular carcinoma awaiting liver transplantation. J Gastrointest Surg 11:1328–1332

    Article  PubMed  Google Scholar 

  24. Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observation studies for causal effects. Biometrika 79:516–524

    Google Scholar 

  25. Rosenbaum PR (1984) Conditional permutation tests and the propensity score in observational studies. J Am Stat Assoc 79:565–574

    Article  Google Scholar 

  26. Marchesini G, Moscatiello S, Di Domizio S, Forlani G (2008) Obesity-associated liver disease. J Clin Endocrinol Metab 93(11 Suppl 1):S74–S80

    Article  PubMed  CAS  Google Scholar 

  27. Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AM (2004) Obesity and hepatocellular carcinoma. Gastroenterology 127(5 Suppl 1):S97–S103

    Article  PubMed  CAS  Google Scholar 

  28. Kim WR, Therneau TM, Benson JT, Kremers WK, Rosen CB, Gores GJ et al (2006) Deaths on the liver transplant waiting list: an analysis of competing risks. Hepatology 43(2):345–351

    Article  PubMed  CAS  Google Scholar 

  29. Kim WR, Biggins SW, Kremers WK, Wiesner RH, Kamath PS, Benson JT et al (2008) Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med 359(10):1018–1026

    Article  PubMed  CAS  Google Scholar 

  30. Gotthardt D, Weiss KH, Baumgartner M, Zahn A, Stremmel W, Schmidt J et al (2009) Limitations of the MELD score in predicting mortality or need for removal from waiting list in patients awaiting liver transplantation. BMC Gastroenterol 9:72

    Article  PubMed  Google Scholar 

  31. Ioannou G, Perkins JD, Carithers RL Jr (2008) Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology 134(5):1342–1351

    Article  PubMed  Google Scholar 

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Acknowledgements

Dr. Jean-Francois Geschwind is a consultant for Biosphere Medical, Biocompatibles, Bayer Healthcare and has grant support from Biospheres, Biocompatibles, MDS Nordion, Genentech, Philips Medical, Bayer Healthcare. Contect Vision, Gideon.

Conflict of interest

The other authors declare they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21287, USA

    Constantine Frangakis & Yong Chen

  2. Department of Vascular and Interventional Radiology, Johns Hopkins University, Baltimore, MD, 21287, USA

    Jean-Francois Geschwind, Daniel Kim, Kelvin Hong, Eleni Liapi & Christos S. Georgiades

  3. Department of Transplant Hepatology, Johns Hopkins University, Baltimore, MD, 21287, USA

    Ayman Koteish

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  1. Constantine Frangakis
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  2. Jean-Francois Geschwind
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Correspondence to Christos S. Georgiades.

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Frangakis, C., Geschwind, JF., Kim, D. et al. Chemoembolization Decreases Drop-Off Risk of Hepatocellular Carcinoma Patients on the Liver Transplant List. Cardiovasc Intervent Radiol 34, 1254–1261 (2011). https://doi.org/10.1007/s00270-010-0077-7

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  • DOI: https://doi.org/10.1007/s00270-010-0077-7

Keywords

  • Chemoembolization
  • Liver transplantation
  • HCC
  • Milan criteria
  • Drop off risk