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BCLC 2022 update: Important advances, but missing external beam radiotherapy

  • Author Footnotes
    † On behalf of the ASTRO Primary Liver Tumor Taskforce
    Christopher Leigh Hallemeier
    Correspondence
    Corresponding author. Address: 100 1st St SW, Rochester, MN 55902, United States. Tel.: 507-284-8227, fax: 507-284-0079.
    Footnotes
    † On behalf of the ASTRO Primary Liver Tumor Taskforce
    Affiliations
    Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
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  • Author Footnotes
    † On behalf of the ASTRO Primary Liver Tumor Taskforce
    Smith Apisarnthanarax
    Footnotes
    † On behalf of the ASTRO Primary Liver Tumor Taskforce
    Affiliations
    Department of Radiation Oncology, University of Washington, Seattle, WA, USA
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  • Laura Ann Dawson
    Affiliations
    Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
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  • Author Footnotes
    † On behalf of the ASTRO Primary Liver Tumor Taskforce
Published:January 02, 2022DOI:https://doi.org/10.1016/j.jhep.2021.12.029

      Linked Article

      • BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update
        Journal of HepatologyVol. 76Issue 3
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          There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers.
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      • Reply to: “Correspondence on the <BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update>”
        Journal of HepatologyVol. 76Issue 5
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          We appreciate the interest garnered by the BCLC 2022 model update. The new version has incorporated the evidence-based novelties generated in recent years, while also adding a section devoted to clinical decision making at the time of first evaluation and during a patient’s clinical evolution. No clinical practice guideline or recommendation review will ever have enough granularity to firmly recommend the most beneficial approach for an individual patient.
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      To the Editor:
      Congratulations to the Barcelona Clinic Liver Cancer (BCLC) group on the 2022 update of the staging, prognosis and treatment guidelines for hepatocellular carcinoma (HCC), which are commonly cited to guide clinical decision-making for HCC worldwide.
      • Reig M.
      • Forner A.
      • Rimola J.
      • Ferrer-Fabrega J.
      • Burrel M.
      • Garcia-Criado A.
      • et al.
      BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update.
      This update of the 2018 guidelines incorporates recent, practice changing trials of systemic therapies in patients with advanced HCC (BCLC C). The BCLC group has incorporated clinical decision making when the “first treatment option” is not feasible or if there is progression, which the group refers to as “treatment stage migration” (TSM). In this context, transarterial radioembolization (TARE) has been incorporated as an option for select patients with BCLC 0-A HCC on the basis of a recent retrospective study.
      • Salem R.
      • Johnson G.E.
      • Kim E.
      • Riaz A.
      • Bishay V.
      • Boucher E.
      • et al.
      Yttrium-90 radioembolization for the treatment of solitary, unresectable HCC: the LEGACY study.
      We agree with the emphasis on a multi-disciplinary approach to HCC, which includes input from hepatology, surgery, radiology, medical oncology, interventional radiology and radiation oncology.
      It is notable that the 2022 updated guidelines do not include external beam radiotherapy (EBRT) as a treatment option in the algorithms for HCC, which is surprising in the context of expanded treatment options that are commonly used when considering “TSM.” In addition to numerous retrospective studies, multiple prospective studies from multiple continents have demonstrated the safety and efficacy of EBRT, including stereotactic body radiotherapy and proton beam therapy (PBT), for all BCLC stages. A few important randomized controlled trials (RCTs) have been published since the 2018 BCLC update. For patients with recurrent BCLC A-B HCC, a phase III non-inferiority RCT comparing PBT vs. radiofrequency ablation (RFA) demonstrated that PBT was associated with lower risk of severe toxicity and liver decompensation, and similar local progression-free survival and survival (4 year survival ∼75%).
      • Kim T.H.
      • Koh Y.H.
      • Kim B.H.
      • Kim M.J.
      • Lee J.H.
      • Park B.
      • et al.
      Proton beam radiotherapy vs. radiofrequency ablation for recurrent hepatocellular carcinoma: a randomized phase III trial.
      For patients with HCC with macrovascular invasion, a phase III RCT demonstrated superior survival with transarterial chemoembolization + EBRT compared to sorafenib alone.
      • Yoon S.M.
      • Ryoo B.Y.
      • Lee S.J.
      • Kim J.H.
      • Shin J.H.
      • An J.H.
      • et al.
      Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial.
      For patients with macrovascular invasion amenable to surgical resection, a phase III RCT demonstrated superior survival with pre-operative EBRT compared to resection alone.
      • Wei X.
      • Jiang Y.
      • Zhang X.
      • Feng S.
      • Zhou B.
      • Ye X.
      • et al.
      Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study.
      Results of these phase III RCTs confirm findings from non-randomized studies.
      The American Society for Radiation Oncology (ASTRO) recently published evidence-based practice guidelines for the use of EBRT for primary liver cancers.
      • Apisarnthanarax S.
      • Barry A.
      • Cao M.
      • Czito B.
      • DeMatteo R.
      • Drinane M.
      • et al.
      External beam radiation therapy for primary liver cancers: an ASTRO clinical practice guideline.
      The guidelines were developed by a multidisciplinary task force with representatives and peer reviewers from the American Society of Clinical Oncology (ASCO), American Society of Transplant Surgeons (ASTS), and the Society of Surgical Oncology (SSO). The guidelines have been endorsed by the European Society for Therapeutic Radiation Oncology (ESTRO), ASTS, and SSO. The guidelines are based on systematic review of published evidence, with consensus recommendations created using a modified Delphi approach. Based on a moderate or low quality of evidence, a strong recommendation was made for the use of EBRT as a potential first-line treatment option in patients with liver-confined HCC who are not candidates for surgery or ablation, as consolidative therapy after incomplete response to other liver-directed therapies, and as a salvage option for local recurrence. Based on a moderate or low quality of evidence, a conditional recommendation was made for the use of EBRT sequenced with systemic or catheter-based therapies for patients with multifocal or unresectable HCC or those with macrovascular invasion. Based on a low or moderate quality of evidence, a conditional recommendation was made for the use of EBRT as a bridge to transplant or prior to surgery in carefully selected patients with macrovascular invasion. Based on a low level of evidence, a conditional recommendation was made for palliative EBRT of symptomatic HCC.
      Recent clinical practice guidelines from major groups worldwide including National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO),
      • Vogel A.
      • Cervantes A.
      • Chau I.
      • Daniele B.
      • Llovet J.M.
      • Meyer T.
      • et al.
      Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
      American Association for the Study of Liver Diseases (AASLD),
      • Marrero J.A.
      • Kulik L.M.
      • Sirlin C.B.
      • Zhu A.X.
      • Finn R.S.
      • Abecassis M.M.
      • et al.
      Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver Diseases.
      and Asia Pacific Association for the Study of the Liver (APASL)
      • Omata M.
      • Cheng A.L.
      • Kokudo N.
      • Kudo M.
      • Lee J.M.
      • Jia J.
      • et al.
      Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update.
      include EBRT as a treatment option for select patients with HCC, while also acknowledging the need for more data. For example, current NCCN guidelines include ablation, embolization, and EBRT as appropriate non-surgical treatment options for patients with liver-confined HCC.
      In our opinion, the current available evidence supports the incorporation of EBRT into BCLC guidelines, especially when “first treatment options” are not feasible or suitable, or if there is progression after first treatment. For future updates of the BCLC guidelines, we propose inclusion of EBRT as per recommendations of the ASTRO Guidelines: 1) for patients with BCLC 0-A HCC, EBRT should be considered as an alternative non-surgical treatment (along with ablation or embolization), either as definitive therapy or as a bridge to transplant; 2) for patients with BCLC B-C, EBRT is a treatment option with or without embolization or systemic therapy; 3) for patients with BCLC D HCC, EBRT should be considered as a palliative treatment for tumor-related pain. We acknowledge the importance of current and future RCTs for all therapies in refining HCC treatment strategies, and we strongly support further RCTs of EBRT for HCC.

      Financial support

      The authors received no financial support to produce this manuscript.

      Authors’ contributions

      CLH, SA, and LAD contributed to concept and design and writing of article.

      Conflicts of interest

      The authors declare no conflicts of interest that pertain to this work.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following are the supplementary data to this article:

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