Skip to main content
SpringerLink
Log in

Transarterial radioembolization in patients with hepatocellular carcinoma of intermediate B2 substage

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Patients with hepatocellular carcinoma (HCC) of intermediate stage (BCLC-B according to the Barcelona Clinic Liver Cancer classification) are a heterogeneous group with different degrees of liver function impairment and tumour burden. The recommended treatment is transarterial chemoembolization (TACE). However, patients in this group may be judged as poor candidates for TACE because the risk-benefit ratio is low. Such patients may receive transarterial radioembolization (TARE) only by entering a clinical trial. Experts have proposed that the stage could be further divided into four substages based on available evidence of treatment benefit. We report here, for the first time, the outcome in patients with BCLC-B2 substage HCC treated with TARE.

Methods

A retrospective analysis of the survival of 126 patients with BCLC-B2 substage HCC treated with TARE in three European hospitals was performed.

Results

Overall median survival in patients with BCLC-B2 substage was not significantly different in relation to tumour characteristics; 19.35 months (95% CI 8.27–30.42 months) in patients with a single large (>7 cm) HCC, and 18.43 months (95% CI 15.08–21.77 months) in patients with multinodular HCC (p = 0.27). However, there was a higher proportion of long-term survivors at 36 months among those with a single large tumour (29%) than among those with multiple tumours (16.8%).

Conclusion

Given the poor efficacy of TACE in treating patients with BCLC-B2 substage HCC, TARE treatment could be a better choice, especially in those with a large tumour.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Tsochatzis EA, Fatourou E, O'Beirne J, Meyer T, Burroughs AK. Transarterial chemoembolization and bland embolization for hepatocellular carcinoma. World J Gastroenterol. 2014;20:3069–77.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Marrero JA, Fontana RJ, Barrat A, Askari F, Conjeevaram HS, Su GL, et al. Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology. 2005;41:707–15.

    Article  PubMed  Google Scholar 

  3. Cillo U, Vitale A, Grigoletto F, Farinati F, Brolese A, Zanus G, et al. Prospective validation of the Barcelona Clinic Liver Cancer staging system. J Hepatol. 2006;44:723–31.

    Article  PubMed  Google Scholar 

  4. Guglielmi A, Ruzzenente A, Pachera S, Valdegamberi A, Sandri M, D'Onofrio M, et al. Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response. Am J Gastroenterol. 2008;103:597–604.

    Article  PubMed  Google Scholar 

  5. European Association for the Study of The Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.

    Article  Google Scholar 

  6. Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol. 2007;4:424–32.

    Article  CAS  PubMed  Google Scholar 

  7. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301–14.

    Article  PubMed  Google Scholar 

  8. Marrero JA, Kulik LM, Sirlin C, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723–50. https://doi.org/10.1002/hep.29913.

  9. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.

    Article  PubMed  Google Scholar 

  10. Bolondi L, Burroughs A, Dufour J-F, Galle PR, Mazzaferro V, Piscaglia F, et al. Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2013;32:348–59.

    Article  CAS  Google Scholar 

  11. Golfieri R, Bargellini I, Spreafico C, Trevisani F. Patients with Barcelona Clinic Liver Cancer stages B and C hepatocellular carcinoma: time for a subclassification. Liver Cancer. 2018. https://doi.org/10.1159/000489791.

  12. Raoul J-L, 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;37:212–20.

    Article  PubMed  Google Scholar 

  13. Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138:52–64.

    Article  CAS  PubMed  Google Scholar 

  14. Hilgard P, Hamami M, El Fouly A, Scherag A, Müller S, Ertle J, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology. 2010;52:1741–9.

    Article  CAS  PubMed  Google Scholar 

  15. Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona Clinic Liver Cancer stages: a European evaluation. Hepatology. 2011;54:868–78.

    Article  PubMed  Google Scholar 

  16. Sangro B, Iñarrairaegui M, Bilbao JI. Radioembolization for hepatocellular carcinoma. J Hepatol. 2012;56:464–73.

    Article  PubMed  Google Scholar 

  17. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–55.

    Article  PubMed  Google Scholar 

  18. Golfieri R, Renzulli M, Mosconi C, Forlani L, Giampalma E, Piscaglia F, et al. Hepatocellular carcinoma responding to superselective transarterial chemoembolization: an issue of nodule dimension? J Vasc Interv Radiol. 2013;24:509–17.

    Article  PubMed  Google Scholar 

  19. Takayasu K, Arii S, Kudo M, Ichida T, Matsui O, Izumi N, et al. Superselective transarterial chemoembolization for hepatocellular carcinoma. Validation of treatment algorithm proposed by Japanese guidelines. J Hepatol. 2012;56:886–92.

    Article  PubMed  Google Scholar 

  20. Golfieri R, Cappelli A, Cucchetti A, Piscaglia F, Carpenzano M, Peri E, et al. Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (5 cm) hepatocellular carcinomas. Hepatology. 2011;53:1580–9.

    Article  PubMed  Google Scholar 

  21. Kulik LM, Carr BI, Mulcahy MF, Lewandowski RJ, Atassi B, Ryu RK, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2008;47:71–81.

    Article  PubMed  Google Scholar 

  22. Kallini JR, Gabr A, Salem R, Lewandowski RJ. Transarterial radioembolization with yttrium-90 for the treatment of hepatocellular carcinoma. Adv Ther. 2016;33:699–714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Padia SA, Lewandowski RJ, Johnson GE, Sze DY, Ward TJ, Gaba RC, et al. Radioembolization of hepatic malignancies: background, quality improvement guidelines, and future directions. J Vasc Interv Radiol. 2017;28:1–15.

    Article  PubMed  Google Scholar 

  24. Andreana L, Isgrò G, Marelli L, Davies N, Yu D, Navalkissoor S, et al. Treatment of hepatocellular carcinoma (HCC) by intra-arterial infusion of radio-emitter compounds: trans-arterial radio-embolisation of HCC. Cancer Treat Rev. 2012;38:641–9.

    Article  CAS  PubMed  Google Scholar 

  25. Iñarrairaegui M, Pardo F, Bilbao JI, Rotellar F, Benito A, D'Avola D, et al. Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma. Eur J Surg Oncol. 2012;38:594–601.

    Article  PubMed  Google Scholar 

  26. Lewandowski RJ, Kulik LM, Riaz A, Senthilnathan S, Mulcahy MF, Ryu RK, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9:1920–8.

    Article  CAS  PubMed  Google Scholar 

  27. El Fouly A, Ertle J, El Dorry A, Shaker MK, Dechêne A, Abdella H, et al. In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int. 2015;35:627–35.

    Article  CAS  PubMed  Google Scholar 

  28. Kooby DA, Egnatashvili V, Srinivasan S, Chamsuddin A, Delman KA, Kauh J, et al. Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21:224–30.

    Article  PubMed  Google Scholar 

  29. Kim DY, Han KH. Transarterial chemoembolization versus transarterial radioembolization in hepatocellular carcinoma: optimization of selecting treatment modality. Hepatol Int. 2016;10:883–92.

    Article  PubMed  Google Scholar 

  30. Kim HC. Radioembolization for the treatment of hepatocellular carcinoma. Clin Mol Hepatol. 2017;23:109–14.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Salem R, Lewandowski RJ, Kulik L, Wang E, Riaz A, Ryu RK, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140:497–507.

    Article  PubMed  Google Scholar 

  32. Salem R, Gilbertsen M, Butt Z, Memon K, Vouche M, Hickey R, et al. Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clin Gastroenterol Hepatol. 2013;11:1358–65.

    Article  PubMed  Google Scholar 

  33. Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2016;151:1155–63.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Moreno-Luna LE, Yang JD, Sanchez W, Paz-Fumagalli R, Harnois DM, Mettler TA, et al. Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2013;36:714–23.

    Article  PubMed  Google Scholar 

  35. Carr BI, Kondragunta V, Buch SC, Branch RA. Therapeutic equivalence in survival for hepatic arterial chemoembolization and yttrium 90 microsphere treatments in unresectable hepatocellular carcinoma: a two-cohort study. Cancer. 2010;116:1305–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pitton MB, Kloeckner R, Ruckes C, Wirth GM, Eichhorn W, Wörns MA, et al. Randomized comparison of selective internal radiotherapy (SIRT) versus drug-eluting bead transarterial chemoembolization (DEB-TACE) for the treatment of hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2015;38:352–60.

    Article  PubMed  Google Scholar 

  37. Facciorusso A, Serviddio G, Muscatiello N. Transarterial radioembolization vs chemoembolization for hepatocarcinoma patients: a systematic review and meta-analysis. World J Hepatol. 2016;8:770–8.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ha Y, Shim JH, Kim S-O, Kim KM, Lim Y-S, Lee HC. Clinical appraisal of the recently proposed Barcelona Clinic Liver Cancer stage B subclassification by survival analysis. J Gastroenterol Hepatol. 2014;29:787–93.

    Article  PubMed  Google Scholar 

  39. Wang J-H, Kee K-M, Lin C-Y, Hung CH, Chen CH, Lee CM, et al. Validation and modification of a proposed substaging system for patients with intermediate hepatocellular carcinoma. J Gastroenterol Hepatol. 2015;30:358–63.

    Article  CAS  PubMed  Google Scholar 

  40. Weinmann A, Koch S, Sprinzl M, Kloeckner R, Schulze-Bergkamen H, Düber C, et al. Survival analysis of proposed BCLC-B subgroups in hepatocellular carcinoma patients. Liver Int. 2015;35:591–600.

    Article  PubMed  Google Scholar 

  41. Yamakado K, Miyayama S, Hirota S, Mizunuma K, Nakamura K, Inaba Y, et al. Prognosis of patients with intermediate-stage hepatocellular carcinomas based on the Child-Pugh score: subclassifying the intermediate stage (Barcelona Clinic Liver Cancer stage B). Jpn J Radiol. 2014;32:644–9.

    Article  PubMed  Google Scholar 

  42. Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology. 2013;57:1826–37.

    Article  CAS  PubMed  Google Scholar 

  43. Kudo M, Arizumi T, Ueshima K, Sakurai T, Kitano M, Nishida N. Subclassification of BCLC B stage hepatocellular carcinoma and treatment strategies: proposal of modified Bolondi’s subclassification (Kinki criteria). Dig Dis. 2015;33:751–8.

    Article  PubMed  Google Scholar 

  44. Kudo M. Heterogeneity and subclassification of Barcelona Clinic Liver Cancer stage B. Liver Cancer. 2016;5:91–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Salem R, Gabr A, Riaz A, Mora R, Ali R, Abecassis M, et al. Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience. Hepatology. 2017. https://doi.org/10.1002/hep.29691.

  46. Giannini EG, Moscatelli A, Pellegatta G, Vitale A, Farinati F, Ciccarese F, et al. Application of the intermediate-stage subclassification to patients with untreated hepatocellular carcinoma. Am J Gastroenterol. 2016;111:70–7.

    Article  CAS  PubMed  Google Scholar 

  47. Kim JH, Shim JH, Lee HC, Sung KB, Ko HK, Ko GY, et al. New intermediate-stage subclassification for patients with hepatocellular carcinoma treated with transarterial chemoembolization. Liver Int. 2017;37:1861–8.

    Article  CAS  PubMed  Google Scholar 

  48. Scaffaro LA, Stella SF, Alvares-Da-Silva MR, Kruel CDP. Survival rates according to Barcelona Clinic Liver Cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma. World J Hepatol. 2015;7:628–32.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Terzi E, Piscaglia F, Forlani L, Mosconi C, Renzulli M, Bolondi L, et al. TACE performed in patients with a single nodule of hepatocellular carcinoma. BMC Cancer. 2014;14:601.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Radiology Unit, Department of Diagnostic and Preventive Medicine, University of Bologna, Policlinico di S.Orsola, Via Albertoni 15, 40138, Bologna, Italy

    Alberta Cappelli, Cristina Mosconi, Caterina De Benedittis & Rita Golfieri

  2. Liver Unit, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Avda. Pio XII 36, 31008, Pamplona, Spain

    Paloma Sangro, Iris Deppe & Bruno Sangro

  3. Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Policlinico di S.Orsola, Bologna, Italy

    Eleonora Terzi

  4. Interventional Radiology, Clinica Universidad de Navarra-IDISNA, Pamplona, Spain

    Jose I. Bilbao

  5. Nuclear Medicine, Clinica Universidad de Navarra-IDISNA, Pamplona, Spain

    Macarena Rodriguez-Fraile

  6. Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany

    Jens Ricke

Authors
  1. Alberta Cappelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paloma Sangro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristina Mosconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iris Deppe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eleonora Terzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jose I. Bilbao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Macarena Rodriguez-Fraile
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Caterina De Benedittis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jens Ricke
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rita Golfieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Bruno Sangro
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Alberta Cappelli, Paloma Sangro, Cristina Mosconi, Eleonora Terzi, J Jose I. Bilbao, Jens Ricke, Rita Golfieri and Bruno Sangro participated in the design of the study.

Alberta Cappelli, Paloma Sangro, Cristina Mosconi, Iris Deppe, Eleonora Terzi, Jose I. Bilbao, Macarena Rodriguez-Fraile and Caterina De Benedittis participated in data collection and manuscript preparation.

All authors participated in the elaboration and interpretation of the results and reviewed the final manuscript.

Corresponding authors

Correspondence to Rita Golfieri or Bruno Sangro.

Ethics declarations

Conflicts of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

The study was approved by the Institutional Review Board/Ethics Committee of each hospital. This article does not describe any studies with animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

Additional information

Alberta Cappelli and Paloma Sangro were joint lead authors.

Key points

1. Intermediate stage BCLC-B HCC includes a heterogeneous group of patients with different degrees of liver function impairment and tumour burden in whom the recommended treatment is transarterial chemoembolization (TACE).

2. Patients with BCLC-B stage HCC are sometimes poor candidates for TACE, and transarterial radioembolization (TARE) is then an option in multidisciplinary team discussions.

3. Experts have proposed a subclassification of stage BCLC-B into four substages on the basis of the degree of liver function impairment, tumour burden and performance status.

4. Patients with BCLC-B2 substage HCC with a large tumour could benefit more from TARE treatment.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cappelli, A., Sangro, P., Mosconi, C. et al. Transarterial radioembolization in patients with hepatocellular carcinoma of intermediate B2 substage. Eur J Nucl Med Mol Imaging 46, 661–668 (2019). https://doi.org/10.1007/s00259-018-4152-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-018-4152-7

Keywords

Search

Navigation