Hepatology International

, Volume 5, Issue 4, pp 975–984

Early identification of poor responders to transarterial chemoembolization for hepatocellular carcinoma

  • Ya-Ju Tsai
  • Chia-Yang Hsu
  • Yi-Hsiang Huang
  • Chien-Wei Su
  • Han-Chieh Lin
  • Rheun-Chuan Lee
  • Jen-Huey Chiang
  • Teh-Ia Huo
  • Shou-Dong Lee
Original Article

Abstract

Purpose

Transarterial chemoembolization (TACE) is used to treat unresectable hepatocellular carcinoma (HCC). However, HCC patients may have an even shorter survival after TACE. This study aimed to identify poor responders to TACE at an early stage.

Patients and methods

A total of 624 and 122 patients with HCC undergoing TACE and best supportive care (BSC), respectively, were analyzed. Poor responders were defined as patients who died after TACE or had viable tumor(s), but not eligible for further treatment at 3 months of treatment.

Results

A total of 102 (16%) patients were identified as poor responders. Poor responders had a significantly decreased long-term survival than other patients receiving TACE and a tendency of higher risk of mortality than patients receiving BSC (p < 0.001 and p = 0.054, respectively). The comparison of 24-month survival showed significantly worse outcome in poor responders than patients receiving BSC (p = 0.04). Serum α-fetoprotein (AFP) level >40 ng/mL (p = 0.024) and albumin level 3.8 g/dL (p = 0.016), Child-Turcotte-Pugh (CTP) class B (p = 0.011), performance status 1 (p < 0.001), total tumor volume (TTV) >65 cm3 (p = 0.001), and vascular invasion (p = 0.005) were independent risk factors predicting poor response at 3 months in the multivariate logistic regression analysis. Among the four HCC staging systems, the Barcelona Clinic Liver Cancer (BCLC) classification showed the highest predictive accuracy for the identification of poor responders.

Conclusions

Poor responders have an increased risk of mortality due to rapid disease progression after TACE. Advanced BCLC stages may better predict a poor response to TACE.

Keywords

Barcelona Clinic Liver Cancer (BCLC) Best supportive care Hepatocellular carcinoma Transarterial chemoembolization Total tumor volume 

Abbreviations

AASLD

American Association of the Study of Liver Disease

AFP

α-Fetoprotein

BCLC

Barcelona Clinic Liver Cancer

BSC

Best supportive care

CI

Confidence interval

CLIP

Cancer of the Liver Italian Program

CT

Computed tomography

CTP

Child-Turcotte-Pugh

HBV

Hepatitis B virus

HCV

Hepatitis C virus

HCC

Hepatocellular carcinoma

MRI

Magnetic resonance imaging

SD

Standard deviation

TACE

Transarterial chemoembolization

TTV

Total tumor volume

References

  1. 1.
    Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, Kudo M, Lee JM, Choi BI, Poon RT, Shiina S, Cheng AL, Jia JD, Obi S, Han KH, Jafri W, Chow P, Lim SG, Chawla YK, Budihusodo U, Gani RA, Lesmana CR, Putranto TA, Liaw YF, Sarin SK. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 2010;4:439–474PubMedCrossRefGoogle Scholar
  2. 2.
    Yuen MF, Hou JL, Chutaputti A, Asia Pacific Working Party on Prevention of Hepatocellular Carcinoma. Hepatocellular carcinoma in the Asia pacific region. J Gastroenterol Hepatol 2009;24:346–353PubMedCrossRefGoogle Scholar
  3. 3.
    Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002;35:519–524PubMedCrossRefGoogle Scholar
  4. 4.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208–1236PubMedCrossRefGoogle Scholar
  5. 5.
    Han KH, Lee JT, Seong J. Treatment of non-resectable hepatocellular carcinoma. J Gastroenterol Hepatol 2002;17(Suppl 3):s424–s427PubMedCrossRefGoogle Scholar
  6. 6.
    Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37:429–442PubMedCrossRefGoogle Scholar
  7. 7.
    Hsu CY, Huang YH, Chiang JH, Lin HC, Su CW, Lee PC, Lee FY, Huo TI, Lee SD. Transarterial chemoembolization in patients with hepatocellular carcinoma and renal insufficiency. J Clin Gastroenterol 2010;44:e171–e177PubMedGoogle Scholar
  8. 8.
    Hsu CY, Huang YH, Su CW, Lin HC, Chiang JH, Lee PC, Lee FY, Huo TI, Lee SD. Renal failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization. Liver Int 2010;30:77–84PubMedCrossRefGoogle Scholar
  9. 9.
    Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, Matsuyama Y, Nakanuma Y, Kojiro M, Makuuchi M, Yamaoka Y. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 2006;131:461–469PubMedCrossRefGoogle Scholar
  10. 10.
    Bruix J, Llovet JM, Castells A, Montana X, Bru C, Ayuso MC, Vilana R, Rodes J. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: Results of a randomized, controlled trial in a single institution. Hepatology 1998;27:1578–1583PubMedCrossRefGoogle Scholar
  11. 11.
    CLIP Group (Cancer of the Liver Italian Program) Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial. Lancet 1998;352:17–20.Google Scholar
  12. 12.
    Grieco A, Pompili M, Caminiti G, Miele L, Covino M, Alfei B, Rapaccini GL, Gasbarrini G. Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre. Gut 2005;54:411–418PubMedCrossRefGoogle Scholar
  13. 13.
    Hsu CY, Huang YH, Su CW, Lin HC, Lee PC, Loong CC, Chiang JH, Huo TI, Lee SD. Selecting an optimal staging system for Hepatocellular carcinoma: comparison of 5 currently used prognostic models. Cancer 2010;116:3006–3014PubMedCrossRefGoogle Scholar
  14. 14.
    Huang YH, Chen CH, Chang TT, Chen SC, Wang SY, Lee HS, Lin PW, Huang GT, Sheu JC, Tsai HM, Lee PC, Chau GY, Lui WY, Lee SD, Wu JC. Evaluation of predictive value of CLIP Okuda, TNM and JIS staging systems for hepatocellular carcinoma patients undergoing surgery. J Gastroenterol Hepatol 2005;20:765–771PubMedCrossRefGoogle Scholar
  15. 15.
    Hsu CY, Huang YH, Hsia CY, Su CW, Lin HC, Loong CC, Chiou YY, Chiang JH, Lee PC, Huo TI, Lee SD. A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring system. J Hepatol 2010;53:108–117PubMedCrossRefGoogle Scholar
  16. 16.
    Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421–430PubMedCrossRefGoogle Scholar
  17. 17.
    Grant BF, Dufour MC, Harford TC. Epidemiology of alcoholic liver disease. Semin Liver Dis 1988;8:12–25PubMedCrossRefGoogle Scholar
  18. 18.
    Huo TI, Huang YH, Lin HC, Wu JC, Chiang JH, Lee PC, Chang FY, Lee SD. Proposal of a modified Cancer of the Liver Italian Program staging system based on the model for end-stage liver disease for patients with hepatocellular carcinoma undergoing loco-regional therapy. Am J Gastroenterol 2006;101:975–982PubMedCrossRefGoogle Scholar
  19. 19.
    Kikuchi LO, Paranagua-Vezozzo DC, Chagas AL, Mello ES, Alves VA, Farias AQ, Pietrobon R, Carriho FJ. Nodules less than 20 mm and vascular invasion are predictors of survival in small hepatocellular carcinoma. J Clin Gastroenterol 2009;43:191–195PubMedCrossRefGoogle Scholar
  20. 20.
    Liver Including Intrahepatic Bile Ducts. In Greene F, Page D, Fleming I, eds. American Joint Committee on Cancer Staging Manual. 6th ed. New York: Springer, 2002;131–144Google Scholar
  21. 21.
    The Cancer of the Liver Italian Program (CLIP) Investigators. Prospective validation of the CLIP score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000;31:840–845Google Scholar
  22. 22.
    Brown DB, Chapman WC, Cook RD, Kerr JR, Gould JE, Pilgram TK, Darcy MD. Chemoembolization of hepatocellular carcinoma: Patient status at presentation and outcome over 15 years at a single center. AJR Am J Roentgenol 2008;190:608–615PubMedCrossRefGoogle Scholar
  23. 23.
    Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. N Engl J Med 1995;332:1256–1261Google Scholar
  24. 24.
    Llado L, Virgili J, Figueras J, Valls C, Dominguez J, Rafecas A, Torras J, Fabregat J, Guardiola J, Jaurrieta E. A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer 2000;88:50–57PubMedCrossRefGoogle Scholar
  25. 25.
    Toso C, Asthana S, Bigam DL, Shapiro AM, Kneteman NM. Reassessing selection criteria prior to liver transplantation for hepatocellular carcinoma utilizing the Scientific Registry of Transplant Recipients database. Hepatology 2009;49:832–838PubMedCrossRefGoogle Scholar
  26. 26.
    Toso C, Trotter J, Wei A, Bigam DL, Shah S, Lancaster J, Grant DR, Greig PD, Shapiro AM, Kneteman NM. Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 2008;14:1107–1115PubMedCrossRefGoogle Scholar
  27. 27.
    Camma C, Di Marco V, Cabibbo G, Latteri F, Sandonato L, Parisi P, Enea M, Attanasio M, Galia M, Alessi N, Licata A, Latteri MA, Craxi A. Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems. Aliment Pharmacol Ther 2008;28:62–75PubMedCrossRefGoogle Scholar
  28. 28.
    Chan AO, Yuen MF, Hui CK, Tso WK, Lai CL. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer 2002;94:1747–1752PubMedCrossRefGoogle Scholar
  29. 29.
    Carr BI, Pancoska P, Branch RA. Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study. Hepatol Int 2009;4:396–405PubMedCrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2011

Authors and Affiliations

  • Ya-Ju Tsai
    • 1
    • 2
    • 3
  • Chia-Yang Hsu
    • 4
    • 5
    • 6
  • Yi-Hsiang Huang
    • 7
  • Chien-Wei Su
    • 4
    • 5
  • Han-Chieh Lin
    • 4
    • 5
  • Rheun-Chuan Lee
    • 4
    • 8
  • Jen-Huey Chiang
    • 4
    • 8
  • Teh-Ia Huo
    • 5
    • 9
  • Shou-Dong Lee
    • 4
    • 5
  1. 1.School of NursingNational Yang-Ming UniversityTaipeiTaiwan
  2. 2.Department of NursingTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.School of NursingUniversity of MichiganAnn ArborUSA
  4. 4.Faculty of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  5. 5.Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  6. 6.Department of MedicineNational Yang-Ming University HospitalYilanTaiwan
  7. 7.Institute of Clinical MedicineNational Yang-Ming UniversityTaipeiTaiwan
  8. 8.Department of RadiologyTaipei Veterans General HospitalTaipeiTaiwan
  9. 9.Institute of PharmacologyNational Yang-Ming UniversityTaipeiTaiwan

Personalised recommendations