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Heterogeneity of intermediate-stage HCC necessitates personalized management including surgery

Nature Reviews Clinical Oncology volume 12, page 10 (2015)Cite this article

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We would like to thank Gao et al. for their correspondence (Heterogeneity of intermediate-stage HCC necessitates personalized management including surgery. Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2014.122-c1)1 on our recent Review (Treatment of intermediate-stage hepatocellular carcinoma Nat. Rev. Clin. Oncol. 11, 525–535; 2014).2 In our Review, we outlined the current approaches to stratifying patients with intermediate-stage hepatocellular carcinoma (HCC), and discussed the potential heterogeneity that remains among this population. We stated that transarterial chemoembolization (TACE) is considered the standard treatment for intermediate-stage HCC, but emphasized that not all patients with intermediate-stage HCC are good candidates for TACE; those patients who are not candidates for TACE or patients in whom TACE has failed should be considered for other treatments, including sorafenib and radioembolization. In their correspondence, Gao et al.1 criticized our Review for stating that TACE and sorafenib should be the only standard treatments for intermediate-stage HCC (a paradigm that they disagree with), whereas this statement is in fact far removed from the message delivered in our Review. Furthermore, Gao et al.1 claim that the Barcelona Clinic Liver Cancer (BCLC) treatment recommendations3 are based on findings in populations of patients with intermediate-stage HCC as a whole and, therefore, do not provide guidance as to which modality will yield the best result in individual patients. As a result, they state that deviations from the guidelines are highly frequent in clinical practice.1 Guidelines are developed to help patients, health practitioners, health-care providers and governments decide which treatment option is most appropriate for specific conditions and/or under particular circumstances.4 Such recommendations should be based on the strongest scientific evidence, but of course their application to the treatment of individual patients should take into account several clinical factors that, for sure, are not detailed in guidelines.

Gao et al.1 go on to highlight the important role of hepatic resection in the recently published Hong Kong Liver Cancer (HKLC) classification.5 This proposed stratification system accepts that hepatic resection can be pursued in subgroups of patients with intermediate-stage or advanced-stage HCC.5 Regrettably, the HKLC classification has several limitations, as summarized in an editorial that accompanied its publication.6 The most-relevant concern is that the study on which the HKLC classification is based was retrospective and, therefore, was probably subject to an unintentional selection bias; patients who were selected for hepatic resection rather than TACE must have had features that gave the surgeon confidence that a good outcome would be achieved, whereas those selected for TACE probably lacked such characteristics, immediately introducing a bias against TACE.7

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References

  1. Gao, Q., Wang, X.-Y., Zhou, J. & Fan, J. Heterogeneity of intermediate-stage HCC necessitates personalized management including surgery. Nat. Rev. Clin. Oncol. http://dx.doi.org/10.1038/nrclinonc.2014.122-c1.

  2. Forner, A., Gilabert, M., Bruix, J. & Raoul, J.-L. Treatment of intermediate-stage hepatocellular carcinoma. Nat. Rev. Clin. Oncol. 11, 525–535 (2014).

    Article  CAS  Google Scholar 

  3. Forner, A., Llovet, J. M. & Bruix, J. Hepatocellular carcinoma. Lancet 379, 1245–1255 (2012).

    Article  Google Scholar 

  4. Qaseem, A., Snow, V., Owens, D. K. & Shekelle, P. The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods. Ann. Intern. Med. 153, 194–199 (2010).

    Article  Google Scholar 

  5. Yau, T. et al. Development of Hong Kong liver cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology 146, 1691–1700.e3 (2014).

    Article  Google Scholar 

  6. Sherman, M. Staging for hepatocellular carcinoma: complex and confusing. Gastroenterology 146, 1599–1602 (2014).

    Article  Google Scholar 

  7. Forner, A., Díaz-González, A., Liccioni, A. & Vilana, R. Prognosis prediction and staging. Best Pract. Res. Clin. Gastroenterol. 28, 855–865 (2014).

    Article  Google Scholar 

  8. Yin, L. et al. Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria: a RCT. J. Hepatol. 61, 82–88 (2014).

    Article  Google Scholar 

  9. Lammer, J. et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc. Interv. Radiol. 33, 41–52 (2010).

    Article  Google Scholar 

  10. Takayasu, K. et al. Superselective transarterial chemoembolization for hepatocellular carcinoma. Validation of treatment algorithm proposed by Japanese guidelines. J. Hepatol. 56, 886–892 (2012).

    Article  Google Scholar 

  11. Malagari, K. et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis. Cardiovasc. Interv. Radiol. 35, 1119–1128 (2012).

    Article  Google Scholar 

  12. Burrel, M. et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design. J. Hepatol. 56, 1330–1335 (2012).

    Article  Google Scholar 

  13. Llovet, J. M., Bru, C. & Bruix, J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin. Liver Dis. 19, 329–338 (1999).

    Article  CAS  Google Scholar 

  14. European Association for the Study of the Liver & European Organisation for Research and Treatment of Cancer. EASL–EORTC Clinical Practice Guidelines: management of hepatocellular carcinoma. J. Hepatol. 56, 908–943 (2012).

  15. Bruix, J. & Sherman, M. Management of hepatocellular carcinoma: an update. Hepatology 53, 1020–1022 (2011).

    Article  Google Scholar 

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Acknowledgements

The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd; Networked Biomedical Research Centre for Hepatic and Digestive Diseases) is funded by the Instituto de Salud Carlos III. The Instituto de Salud Carlos III has also supported the work of A.F. and J.B. (grants PI11/01830 and PI13/01229).

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Authors and Affiliations

  1. Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Networked Biomedical Research Centre for Hepatic and Digestive Diseases (CIBERehd), Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Carrer Villarroel 170, Barcelona, 08036, Spain

    Alejandro Forner & Jordi Bruix

  2. Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, Marseille, 13009, France

    Marine Gilabert & Jean-Luc Raoul

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  1. Alejandro Forner
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Correspondence to Alejandro Forner.

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Competing interests

A.F. has acted as a consultant for Bayer HealthCare. J.B. has acted as a consultant or in an advisory role for ArQule, Bayer, Biocompatibles, Bristol–Myers Squibb, Celgene, Daiichi-Sankyo, Kowa, Lilly, Novartis, Roche, and Terumo. J.-L.R. has acted as a consultant or in an advisory role for Arqule, Bayer HealthCare, Biocompatibles, Bristol–Myers Squibb, and Merck Serono. M.G. declares no competing interests.

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Forner, A., Gilabert, M., Bruix, J. et al. Heterogeneity of intermediate-stage HCC necessitates personalized management including surgery. Nat Rev Clin Oncol 12, 10 (2015). https://doi.org/10.1038/nrclinonc.2014.122-c2

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