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Interventional treatment of hepatocellular carcinoma

      Local therapies are standard of care for most hepatocellular carcinoma (HCC),
      • Llovet J.M.
      • De Baere T.
      • Kulik L.
      • Haber P.K.
      • Greten T.F.
      • Meyer T.
      • et al.
      Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma.
      and image-guided interventions play a predominant role.
      • Cassinotto C.
      • Nogue E.
      • Morell M.
      • Panaro F.
      • Molinari N.
      • Guiu B.
      Changing trends in hepatocellular carcinoma management: results from a nationwide database in the last decade.
      A multidisciplinary approach, technological breakthroughs
      • de Baere T.
      • Tselikas L.
      • Deschamps F.
      • Boige V.
      • Ducreux M.
      • Hollebecque A.
      Advances in transarterial therapies for hepatocellular carcinoma: is novel technology leading to better outcomes?.
      and better patient selection, supported by clinical evidence, are the key factors allowing for this continuous development.
      Improvement in patient selection and treatment allocation implies some granularity in classification of the tumor and patient characteristics that are not yet fully expressed in guidelines. Hence the concept of “therapeutic hierarchy” relies on a multidisciplinary approach and expertise and can be applied for various therapeutic approaches and tumor stages.
      • Vitale A.
      • Trevisani F.
      • Farinati F.
      • Cillo U.
      Treatment of hepatocellular carcinoma in the precision medicine era: from treatment stage migration to therapeutic hierarchy.
      For example, while ablation is recommended in small size tumors and clear diameter thresholds are expressed, tumor location and tumor conspicuity on imaging are not included in any guideline. Possibility of selective vascular access, such as superselective transarterial chemoembolization (TACE) and selective internal radiation therapy (SIRT), provide very high complete response rates when treating small tumors.
      • Reig M.
      • Forner A.
      • Rimola J.
      • Ferrer-Fabrega J.
      • Burrel M.
      • Garcia-Criado A.
      • et al.
      BCLC strategy for prognosis prediction and treatment recommendation Barcelona Clinic Liver Cancer (BCLC) staging system. The 2022 update.
      The same applies to unilobar vs. bilobar tumors. Furthermore, although intra-arterial therapies are mainstream for intermediate HCC, SIRT is also offered to patients with advanced disease, specifically for tumors invading the portal vein branches.
      • 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.
      Evidence-based medicine drives treatment algorithms; thus, interventional treatments are part of all the HCC management guidelines. For early-stage HCC, according to BCLC classification, randomized controlled trials have proven the non-inferiority of ablation vs. resection for selected patients and intra-arterial therapies (notably SIRT) have entered the guidelines in this setting.
      • Reig M.
      • Forner A.
      • Rimola J.
      • Ferrer-Fabrega J.
      • Burrel M.
      • Garcia-Criado A.
      • et al.
      BCLC strategy for prognosis prediction and treatment recommendation Barcelona Clinic Liver Cancer (BCLC) staging system. The 2022 update.
      The combination of ablation and immunotherapies in the neoadjuvant or adjuvant settings are under evaluation, with the aim of reducing the risk of recurrence and relapse.
      For patients with intermediate-stage HCC who are not candidates for liver transplantation or liver resection, intra-arterial therapies are the gold standard. No significant differences have been shown with various delivery platforms used for TACE. SIRT, on the other hand, and now hepatic arterial infusion of chemotherapy (HAIC) are challenging TACE as the first-line option, with promising results both regarding efficacy and safety.
      • Salem R.
      • Gordon A.C.
      • 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.
      ,
      • Li Q.J.
      • He M.K.
      • Chen H.W.
      • Fang W.Q.
      • Zhou Y.M.
      • Xu L.
      • et al.
      Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellular carcinoma: a randomized phase III trial.
      The combination of kinase inhibitors with intra-arterial therapies has not proven to add any benefit but has defined an updated benchmark of what can be expected nowadays with TACE as a standalone treatment. Modern systemic approaches with immune-checkpoint inhibitors together with TACE or SIRT arouse enthusiasm and are also under evaluation in large clinical trials.
      • Palmer D.H.
      • Malagari K.
      • Kulik L.M.
      Role of locoregional therapies in the wake of systemic therapy.
      Patients with advanced HCC are typically not eligible for interventional therapies, and all controlled randomized phase III trials, except the FOHAIC-1 trial using HAIC,
      • Lyu N.
      • Wang X.
      • Li J.B.
      • Lai J.F.
      • Chen Q.F.
      • Li S.L.
      • et al.
      Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: a biomolecular exploratory, randomized, phase III trial (FOHAIC-1).
      have failed to show an OS advantage of intra-arterial therapies. But some patients, mainly those classified as advanced because of performance status or limited portal vein invasion, can be excellent candidates for HAI or SIRT, especially when using personalized dosimetry.
      • Garin E.
      • Palard X.
      • Rolland Y.
      Personalised dosimetry in radioembolisation for HCC: impact on clinical outcome and on trial design.
      More data are needed for SIRT in order to enter the guidelines in this setting, but, on a per patient basis, multidisciplinary discussion can offer it as a valuable option. Once again, the combination of immunomodulating agents with or without antiangiogenic drugs and interventional treatments need to be explored, on the back of their reciprocal potentiating effects.
      Image-guided local immunotherapy
      • Tselikas L.
      • Champiat S.
      • Sheth R.A.
      • Yevich S.
      • Ammari S.
      • Deschamps F.
      • et al.
      Interventional Radiology for local immunotherapy in oncology.
      is of particular interest for patients with both early and advanced stage HCC, and results from studies testing percutaneous and intra-arterial administration routes are awaited. This approach might find a place in the interventional radiology armamentarium in the near future.
      Finally, interventional treatments for HCC are not only well established but also have great potential and their role should increase and be strengthened in the future.

      Financial support

      The authors received no financial support to produce this manuscript.

      Authors’ contributions

      All authors contributed to design, writing, editing of this snapshot.

      Conflict of interest

      Riad Salem: Eisai, Genentech, Astra Zeneca, Sirtex, Boston Sci, Bard, QED Therapeutics. Lambros Tselikas: BMS, Boston Scientific, GE Healthcare, Quantum Surgical. Thierry de Baere: Terumo, Boston Scientific, Guerbet, GE Healthcare.
      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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