Top

Published in:

01-11-2008 | Hepatic and Pancreatic Tumors

Bridging Locoregional Therapy for Hepatocellular Carcinoma Prior to Liver Transplantation

Authors: Jason T. Heckman, MD, Michael B. deVera, MD, J. Wallis Marsh, MD, MBA, Paulo Fontes, MD, Nikhil B. Amesur, MD, Shane E. Holloway, MD, Michael Nalesnik, MD, David A. Geller, MD, Jennifer L. Steel, PhD, T. Clark Gamblin, MD, MS

Published in: Annals of Surgical Oncology | Issue 11/2008

Abstract

Introduction

The impact of locoregional therapy prior to liver transplantation for hepatocellular carcinoma utilizing either transcatheter arterial chemoembolization (TACE), yttrium-90 (⁹⁰Y), radiofrequency ablation (RFA), or resection prior to orthotopic liver transplantation (OLT) is largely unknown. We sought to examine locoregional therapies and their effect on survival compared with transplantation alone.

Methods

A retrospective review of a prospectively collected database.

Results

123 patients were included. Patients were analyzed in two groups. Group I consisted of 50 patients that received therapy (20 TACE; 16 ⁹⁰Y; 13 RFA, 3 resections). Group II consisted of 73 patients transplanted without therapy. Median list time was 28 days (range 2–260 days ) in group I, and 24 days (range 1–380 days) in group II. Median time from therapy to OLT was 3.8 months (range 9 days to 68 months). Twelve patients (24%) were successfully downstaged (8 TACE, 2 ⁹⁰Y, 2 RFA/resection). Overall 1-, 3-, and 5-year survival were 81%, 74%, and 74%, respectively. Survival was not statistically significantly different between the two groups (P = 0.53). The 12 patients downstaged did not have a significant difference in survival as compared with the patients who received therapy but did not respond or the patients who were transplanted without therapy (P = 0.76).

Conclusion

Our report addresses locoregional therapy for hepatocellular carcinoma as a bridge to transplant. There was no statistical difference in overall survival between patients treated and those not treated prior to transplant. We provide further evidence that locoregional therapy is a safe tool for patients on the transplant list, does not impact survival, and can downstage selected patients to allow life-saving liver transplantation.

El-Serag HB, Davila JA, Petersen NJ, et al. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003; 139:817–23.PubMed

Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334:693–9.PubMedCrossRef

Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001; 33:1394–403.PubMedCrossRef

Mazzaferro V, Chun YS, Poon RT, et al. Liver transplantation for hepatocellular carcinoma. Ann Surg Oncol 2008

Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999; 30:1434–40.PubMedCrossRef

Yao FY, Bass NM, Nikolai B, et al. A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy. Liver Transpl 2003; 9:684–92.PubMedCrossRef

http://www.unos.org/PoliciesandBylaws2/policies/pdfs/policy_8.pdf. Organ Distribution: Allocation of Livers. Accessed 1 March 2008

Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60:646–9.PubMedCrossRef

Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 2003; 124:91–6.PubMedCrossRef

10.

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5:649–55.PubMedCrossRef

11.

Ebied OM, Federle MP, Carr BI, et al. Evaluation of responses to chemoembolization in patients with unresectable hepatocellular carcinoma. Cancer 2003; 97:1042–50.PubMedCrossRef

12.

Carr BI. Hepatic arterial 90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients. Liver Transpl 2004; 10:S107–10.PubMedCrossRef

13.

Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002; 35:1164–71.PubMedCrossRef

14.

Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002; 359:1734–9.PubMedCrossRef

15.

Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 2002; 224:47–54.PubMedCrossRef

16.

Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37:429–42.PubMedCrossRef

17.

Lesurtel M, Mullhaupt B, Pestalozzi BC, et al. Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis. Am J Transplant 2006; 6:2644–50.PubMedCrossRef

18.

Decaens T, Roudot-Thoraval F, Bresson-Hadni S, et al. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transpl 2005; 11:767–75.PubMedCrossRef

19.

Veltri A, Grosso M, Martina MC, et al. Effect of preoperative radiological treatment of hepatocellular carcinoma before liver transplantation: a retrospective study. Cardiovasc Intervent Radiol 1998; 21:393–8.PubMedCrossRef

20.

Porrett PM, Peterman H, Rosen M, et al. Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl 2006; 12:665–73.PubMedCrossRef

21.

Majno PE, Adam R, Bismuth H, et al. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg 1997; 226:688–701.PubMedCrossRef

22.

Bharat A, Brown DB, Crippin JS, et al. Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival. J Am Coll Surg 2006; 203:411–20.PubMedCrossRef

23.

Graziadei IW, Sandmueller H, Waldenberger P, 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; 9:557–63.PubMedCrossRef

24.

Maddala YK, Stadheim L, Andrews JC, et al. Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization. Liver Transpl 2004; 10:449–55.PubMedCrossRef

25.

Obed A, Beham A, Pullmann K, et al. Patients without hepatocellular carcinoma progression after transarterial chemoembolization benefit from liver transplantation. World J Gastroenterol 2007; 13:761–7.PubMed

26.

Otto G, Heise M, Moench C, et al. Transarterial chemoembolization before liver transplantation in 60 patients with hepatocellular carcinoma. Transplant Proc 2007; 39:537–9.PubMedCrossRef

27.

Bismuth H, Chiche L, Adam R, et al. Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg 1993; 218:145–51.PubMedCrossRef

28.

Fong Y, Sun RL, Jarnagin W, et al. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg 1999; 229:790–9; discussion 799–800.PubMedCrossRef

29.

Figueras J, Jaurrieta E, Valls C, et al. Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy. J Am Coll Surg 2000; 190:580–7.PubMedCrossRef

30.

Poon RT, Fan ST, Lo CM, et al. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 2002; 235:373–82.PubMedCrossRef

31.

Poon RT, Fan ST. Resection prior to liver transplantation for hepatocellular carcinoma: a strategy of optimizing the role of resection and transplantation in cirrhotic patients with preserved liver function. Liver Transpl 2004; 10:813–5.PubMedCrossRef

32.

Belghiti J, Cortes A, Abdalla EK, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 2003; 238:885–92.PubMedCrossRef

33.

Yao FY, Bass NM, Nikolai B, 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; 8:873–83.PubMedCrossRef

34.

Cherqui D, Laurent A, Tayar C, et al. Laparoscopic liver resection for peripheral hepatocellular carcinoma in patients with chronic liver disease: midterm results and perspectives. Ann Surg 2006; 243:499–506.PubMedCrossRef

35.

Hong SN, Lee SY, Choi MS, et al. Comparing the outcomes of radiofrequency ablation and surgery in patients with a single small hepatocellular carcinoma and well-preserved hepatic function. J Clin Gastroenterol 2005; 39:247–52.PubMedCrossRef

36.

Lu DS, Yu NC, Raman SS, et al. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Hepatology 2005; 41:1130–7.PubMedCrossRef

37.

Mazzaferro V, Battiston C, Perrone S, et al. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study. Ann Surg 2004; 240:900–9.PubMedCrossRef

38.

Pompili M, Mirante VG, Rondinara G, et al. Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: Assessment of efficacy at explant analysis and of safety for tumor recurrence. Liver Transpl 2005; 11:1117–26.PubMedCrossRef

39.

Belghiti J. CB, Greig PD, Lencioni R, et al. Treatment before Liver Transplantation for HCC. Ann Surg Oncol 2008; Jan 31(Epub ahead of print)

40.

Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 2005; 16:1627–39.PubMed

41.

Kulik LM, Atassi B, van Holsbeeck L, et al. Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol 2006; 94:572–86.PubMedCrossRef

Title: Bridging Locoregional Therapy for Hepatocellular Carcinoma Prior to Liver Transplantation
Authors: Jason T. Heckman, MD
Michael B. deVera, MD
J. Wallis Marsh, MD, MBA
Paulo Fontes, MD
Nikhil B. Amesur, MD
Shane E. Holloway, MD
Michael Nalesnik, MD
David A. Geller, MD
Jennifer L. Steel, PhD
T. Clark Gamblin, MD, MS
Publication date: 01-11-2008
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 11/2008
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-008-0071-3

At a glance: The STEP trials

Springer Medicine

Bridging Locoregional Therapy for Hepatocellular Carcinoma Prior to Liver Transplantation

Abstract

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2008

Hidden Opportunities in Cytoreductive Surgery for Peritoneal Carcinomatosis of Colorectal Origin

Extrapancreatic Malignancies in Patients with Intraductal Papillary Mucinous Neoplasm of the Pancreas: Prevalence, Associated Factors, and Comparison with Patients with Other Pancreatic Cystic Neoplasms

Intraoperative Radioisotope Injection for Sentinel Lymph Node Biopsy

Prognostic Relevance of Lymph Node Ratio and Number of Resected Nodes after Curative Resection of Ampulla of Vater Carcinoma

Pancreatic Resection of Isolated Metastases from Nonpancreatic Primary Cancers

Extrahepatic Bile Duct Adenocarcinoma: Patients at High-Risk for Local Recurrence Treated with Surgery and Adjuvant Chemoradiation Have an Equivalent Overall Survival to Patients with Standard-Risk Treated with Surgery Alone