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Transarterial radioembolization in patients with hepatocellular carcinoma of intermediate B2 substage

  • Alberta Cappelli
  • Paloma Sangro
  • Cristina Mosconi
  • Iris Deppe
  • Eleonora Terzi
  • Jose I. Bilbao
  • Macarena Rodriguez-Fraile
  • Caterina De Benedittis
  • Jens Ricke
  • Rita GolfieriEmail author
  • Bruno SangroEmail author
Original Article
  • 242 Downloads

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.

Keywords

Hepatocellular carcinoma Transarterial chemoembolization Transarterial radioembolization BCLC-B subclassification 

Notes

Authors’ 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.

Funding

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

Compliance with ethical standards

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.

References

  1. 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.CrossRefGoogle Scholar
  2. 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.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 5.
    European Association for the Study of The Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.CrossRefGoogle Scholar
  6. 6.
    Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol. 2007;4:424–32.CrossRefGoogle Scholar
  7. 7.
    Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301–14.CrossRefGoogle Scholar
  8. 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. 9.
    Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 16.
    Sangro B, Iñarrairaegui M, Bilbao JI. Radioembolization for hepatocellular carcinoma. J Hepatol. 2012;56:464–73.CrossRefGoogle Scholar
  17. 17.
    Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–55.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.CrossRefGoogle Scholar
  27. 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.CrossRefGoogle Scholar
  28. 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.CrossRefGoogle Scholar
  29. 29.
    Kim DY, Han KH. Transarterial chemoembolization versus transarterial radioembolization in hepatocellular carcinoma: optimization of selecting treatment modality. Hepatol Int. 2016;10:883–92.CrossRefGoogle Scholar
  30. 30.
    Kim HC. Radioembolization for the treatment of hepatocellular carcinoma. Clin Mol Hepatol. 2017;23:109–14.CrossRefGoogle Scholar
  31. 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.CrossRefGoogle Scholar
  32. 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.CrossRefGoogle Scholar
  33. 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.CrossRefGoogle Scholar
  34. 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.CrossRefGoogle Scholar
  35. 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.CrossRefGoogle Scholar
  36. 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.CrossRefGoogle Scholar
  37. 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.CrossRefGoogle Scholar
  38. 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.CrossRefGoogle Scholar
  39. 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.CrossRefGoogle Scholar
  40. 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.CrossRefGoogle Scholar
  41. 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.CrossRefGoogle Scholar
  42. 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.CrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 44.
    Kudo M. Heterogeneity and subclassification of Barcelona Clinic Liver Cancer stage B. Liver Cancer. 2016;5:91–6.CrossRefGoogle Scholar
  45. 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. 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.CrossRefGoogle Scholar
  47. 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.CrossRefGoogle Scholar
  48. 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.CrossRefGoogle Scholar
  49. 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.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alberta Cappelli
    • 1
  • Paloma Sangro
    • 2
  • Cristina Mosconi
    • 1
  • Iris Deppe
    • 2
  • Eleonora Terzi
    • 3
  • Jose I. Bilbao
    • 4
  • Macarena Rodriguez-Fraile
    • 5
  • Caterina De Benedittis
    • 1
  • Jens Ricke
    • 6
  • Rita Golfieri
    • 1
    Email author
  • Bruno Sangro
    • 2
    Email author
  1. 1.Radiology Unit, Department of Diagnostic and Preventive MedicineUniversity of Bologna, Policlinico di S.OrsolaBolognaItaly
  2. 2.Liver UnitClinica Universidad de Navarra-IDISNA and CIBEREHDPamplonaSpain
  3. 3.Division of Internal Medicine, Department of Medical and Surgical SciencesUniversity of Bologna, Policlinico di S.OrsolaBolognaItaly
  4. 4.Interventional RadiologyClinica Universidad de Navarra-IDISNAPamplonaSpain
  5. 5.Nuclear MedicineClinica Universidad de Navarra-IDISNAPamplonaSpain
  6. 6.Department of Radiology and Nuclear MedicineUniversity Hospital MagdeburgMagdeburgGermany

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