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CardioVascular and Interventional Radiology

, Volume 40, Issue 3, pp 410–420 | Cite as

Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

  • Minzhi Xing
  • Sonali Sakaria
  • Renumathy Dhanasekaran
  • Samir Parekh
  • James Spivey
  • Stuart J. Knechtle
  • Di Zhang
  • Hyun S. Kim
Clinical Investigation

Abstract

Background and Aims

To evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.

Methods

Our transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.

Results

Of 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).

Conclusions

Bridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.

Keywords

Hepatocellular carcinoma (HCC) Locoregional therapy (LRT) Liver transplantation Embolization Ablation Overall survival Milan criteria 

Abbreviations

BCLC

Barcelona Clinic Liver Cancer Staging System

cTACE

Conventional transarterial chemoembolization

DEB-TACE

Drug-eluting bead transarterial chemoembolization

HCC

Hepatocellular carcinoma

LRT

Locoregional therapy

MELD

Model for end-stage liver disease

OLT

Orthotopic liver transplantation

PVT

Portal vein thrombosis

RFA

Radiofrequency ablation

Y90

Yttrium-90 radioembolization

Notes

Acknowledgements

The authors thank Dr. Jong-Hyeon Jeong in the Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh for his assistance in statistical analysis for this manuscript.

Author Contributions

MX conducted analysis and interpretation of the data, statistical analysis, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. SS was involved in acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and statistical analysis. RD was involved in acquisition of data, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. DZ was involved in the analysis and interpretation of data and statistical analysis. SP was involved in the study concept and design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. JRS was involved in the study concept and design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. SJK was involved in the study concept and design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. HSK was involved in study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, statistical analysis, and study overall supervision. All authors were involved in critically revising the manuscript prior to final submission.

Disclosures

All authors have no financial or other disclosures or relationship with any commercial organization that may have a direct or indirect interest in this manuscript.

Information Concerning Grants

None applicable.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

References

  1. 1.
    Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 2005;9(2):191–211.CrossRefPubMedGoogle Scholar
  2. 2.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMedGoogle Scholar
  3. 3.
    Heckman JT, Devera MB, Marsh JW, Fontes P, Amesur NB, Holloway SE, et al. Bridging locoregional therapy for hepatocellular carcinoma prior to liver transplantation. Ann Surg Oncol. 2008;15(11):3169–77.CrossRefPubMedGoogle Scholar
  4. 4.
    Jarnagin WR. Management of small hepatocellular carcinoma: a review of transplantation, resection, and ablation. Ann Surg Oncol. 2010;17(5):1226–33.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30(6):1434–40.CrossRefPubMedGoogle Scholar
  6. 6.
    Keeffe EB. Summary of guidelines on organ allocation and patient listing for liver transplantation. Liver Transpl Surg. 1998;4(5 Suppl 1):S108–14.PubMedGoogle Scholar
  7. 7.
    Yao FY, Bass NM, Nikolai B, Davern TJ, Kerlan R, Wu V, et al. Liver transplantation for hepatocellular carcinoma: analysis of survival according to the intention-to-treat principle and dropout from the waiting list. Liver Transpl. 2002;8(10):873–83.CrossRefPubMedGoogle Scholar
  8. 8.
    EASL-EORTC Clinical Practice Guidelines. Management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43.CrossRefGoogle Scholar
  9. 9.
    Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429–42.CrossRefPubMedGoogle Scholar
  10. 10.
    Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100(10):698–711.CrossRefPubMedGoogle Scholar
  11. 11.
    Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Dharancy S, Boitard J, Decaens T, Sergent G, Boleslawski E, Duvoux C, et al. Comparison of two techniques of transarterial chemoembolization before liver transplantation for hepatocellular carcinoma: a case–control study. Liver Transpl. 2007;13(5):665–71.CrossRefPubMedGoogle Scholar
  13. 13.
    Majno P, Giostra E, Morel P, Hadengue A, Mentha G. Management of hepatocellular carcinoma in the waiting list before liver transplantation. J Hepatol. 2005;42(1):S134–43.CrossRefPubMedGoogle Scholar
  14. 14.
    Nicolini A, Martinetti L, Crespi S, Maggioni M, Sangiovanni A. Transarterial chemoembolization with epirubicin-eluting beads versus transarterial embolization before liver transplantation for hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21(3):327–32.CrossRefPubMedGoogle Scholar
  15. 15.
    Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, et al. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev. 2011;37(3):212–20.CrossRefPubMedGoogle Scholar
  16. 16.
    Kwan SW, Fidelman N, Ma E, Kerlan RK Jr, Yao FY. Imaging predictors of the response to transarterial chemoembolization in patients with hepatocellular carcinoma: a radiological-pathological correlation. Liver Transpl. 2012;18(6):727–36.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Majno PE, Adam R, Bismuth H, Castaing D, Ariche A, Krissat J, et al. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg. 1997;226(6):688–701.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ravaioli M, Grazi GL, Ercolani G, Fiorentino M, Cescon M, Golfieri R, et al. Partial necrosis on hepatocellular carcinoma nodules facilitates tumor recurrence after liver transplantation. Transplantation. 2004;78(12):1780–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.CrossRefPubMedGoogle Scholar
  20. 20.
    Salem R, Lewandowski RJ, Gates VL, Nutting CW, Murthy R, Rose SC, et al. Research reporting standards for radioembolization of hepatic malignancies. J Vasc Interv Radiol. 2011;22(3):265–78.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Prajapati HJ, Rafi S, Edalat F, Kooby DA, Kim HS. Safety and efficacy of a circumferential clip-based vascular closure device in cirrhotic and coagulopathic patients with hepatocellular carcinoma after doxorubicin drug-eluting beads transarterial chemoembolization. Cardiovasc Interv Radiol. 2014;37(3):664–70.CrossRefGoogle Scholar
  22. 22.
    Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Eguchi S, Hidaka M, Tomonaga T, Miyazaki K, Inokuma T, Takatsuki M, et al. Actual therapeutic efficacy of pre-transplant treatment on hepatocellular carcinoma and its impact on survival after salvage living donor liver transplantation. J Gastroenterol. 2009;44(6):624–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Porrett PM, Peterman H, Rosen M, Sonnad S, Soulen M, Markmann JF, et al. Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl. 2006;12(4):665–73.CrossRefPubMedGoogle Scholar
  25. 25.
    Decaens T, Roudot-Thoraval F, Bresson-Hadni S, Meyer C, Gugenheim J, Durand F, et al. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transpl. 2005;11(7):767–75.CrossRefPubMedGoogle Scholar
  26. 26.
    DuBay DA, Sandroussi C, Kachura JR, Ho CS, Beecroft JR, Vollmer CM, et al. Radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. HPB. 2011;13(1):24–32.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Freeman RB Jr, Steffick DE, Guidinger MK, Farmer DG, Berg CL, Merion RM. Liver and intestine transplantation in the United States, 1997-2006. Am J Transplant. 2008;8(4 Pt 2):958–76.CrossRefPubMedGoogle Scholar
  28. 28.
    Bharat A, Brown DB, Crippin JS, Gould JE, Lowell JA, Shenoy S, et al. Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival. J Am Coll Surg. 2006;203(4):411–20.CrossRefPubMedGoogle Scholar
  29. 29.
    Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35(5):1164–71.CrossRefPubMedGoogle Scholar
  30. 30.
    Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatology. 2010;52(2):762–73.CrossRefPubMedGoogle Scholar
  31. 31.
    Johnson EW, Holck PS, Levy AE, Yeh MM, Yeung RS. The role of tumor ablation in bridging patients to liver transplantation. Arch Surg. 2004;139(8):825–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Graziadei IW, Sandmueller H, Waldenberger P, Koenigsrainer A, Nachbaur K, Jaschke W, et al. Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transpl. 2003;9(6):557–63.CrossRefPubMedGoogle Scholar
  33. 33.
    Schlansky B, Chen Y, Scott DL, Austin D, Naugler WE. Waiting time predicts survival after liver transplantation for hepatocellular carcinoma: a cohort study using the United Network for Organ Sharing registry. Liver Transpl. 2014;20(9):1045–56.CrossRefPubMedGoogle Scholar
  34. 34.
    OPTN/UNOS Liver and Intestinal Organ Transplantation Committee. Conference call interim report. 2013. http://optn.transplant.hrsa.gov/CommitteeReports/interim_main_Liver&IntestinalOrganTransplantationCommittee_7_22_2013_15_44.pdf. Accessed Aug 2014.
  35. 35.
    Heimbach J, Hirose R, Olthoff K, Kim W, Schladt D, Xiong H, et al. Delayed HCC MELD exception score improves disparity in access to liver transplant. http://www.srtr.org/publications/pdf/pres/2013/Delayed_HCC_MELD_Exception_Score_Improves_Disparity_in_Access_to_Liver_Transplant.pdf. Accessed Aug 2014.

Copyright information

© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2016

Authors and Affiliations

  • Minzhi Xing
    • 1
  • Sonali Sakaria
    • 2
  • Renumathy Dhanasekaran
    • 3
  • Samir Parekh
    • 2
  • James Spivey
    • 2
  • Stuart J. Knechtle
    • 4
  • Di Zhang
    • 5
  • Hyun S. Kim
    • 1
    • 6
  1. 1.Interventional Radiology, Department of Radiology and Biomedical ImagingYale School of MedicineNew HavenUSA
  2. 2.Division of Digestive Diseases, Department of MedicineEmory University School of MedicineAtlantaUSA
  3. 3.Division of Gastroenterology and HepatologyStanford University School of MedicinePalo AltoUSA
  4. 4.Division of Transplant Surgery, Department of SurgeryDuke University School of MedicineDurhamUSA
  5. 5.Department of Biostatistics, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  6. 6.Yale Cancer CenterNew HavenUSA

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