title: Systemic therapy for hepatocellular carcinoma: the issue of treatment stage migration and registration of progression using the BCLC-refined RECIST.
abstract: Recent advancements have improved the management of patients with liver cancer. Results of studies have informed how to stage and decide the optimal treatment option for each patient with an adequate balance between risks and benefits. The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy has been widely endorsed for this purpose. This is not a rigid system: One of the key aspects in the management of patients is the optimal timing for systemic treatment initiation and for declaring tumor progression and/or treatment failure. Some patients at intermediate or even early stage may be considered for systemic therapy as options of higher priority may have failed or may not be feasible. Sorafenib is the sole systemic agent that has shown efficacy in phase 3 trials. Other agents (sunitinib, brivanib, linifanib, everolimus, ramucirumab) have failed in terms of safety and/or survival benefit. Optimal sorafenib administration and adequate adherence of the patients are crucial requirements to obtain the benefits of the drug. Because development of adverse events has been shown to correlate with better outcome, careful dose adjustments should be in place while avoiding unnecessary treatment interruption. Furthermore, recent studies have shown that progression at imaging may not translate in poor prognosis and that treatment beyond progression may be considered if there is no option for a second-line research trial.In this review, the authors examine all of the controversial aspects that affect treatment initiation and maintenance, how response to treatment should be evaluated, and define the needs that are faced by current research.
authors.affiliation: Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Reig
authors.affiliation: Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Darnell
authors.affiliation: Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Forner
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rimola
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.affiliation: Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents