Friday, 15 September 2017

ILCA Symposium 2: The HCC-Cholangiocarcinoma Spectrum

Jessica Zucman-Rossi, MD, PhD (France)

  • Elizabeth Brunt, MD (USA)

    The concept that primary carcinomas of the liver are, by definition, either hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCCa) has been questioned by pathologists and described in the literature during the past 100 years. 

  • Presenter: Josep M. Llovet, MD (Spain/USA) 

  • Presenter: Kevin Kim, MD (USA) 

  • Juan Valle, MD (United Kingdom)

    In patients presenting with advanced, inoperable or recurrent cholangiocarcinoma, systemic chemotherapy is established as a cornerstone of therapy; with cisplatin and gemcitabine as a reference regimen based on level 1 evidence. However, its modest efficacy, achieving a median survival of approximately one year, highlights the need to improve treatment regimens. The role of triple-agent combination chemotherapy (e.g. cisplatin- gemcitabine-fluoropyrimidine; cisplatin-gemcitabine-nab-paclitaxel; 5-FU-oxaliplatin-irinotecan), the emergence of new chemotherapy agents (such as acelarin) and novel delivery mechanisms, as well as the role of second-line chemotherapy are areas under active investigation. “Cholangiocarcinoma” is acknowledged to be a collective term for heterogeneous tumours, largely based on anatomical site of origin. Moreover, molecular analyses are improving our understanding of various sub-types of cholangiocarcinoma which, in turn, have identified new areas for investigation. Clinical studies are currently enrolling patients with intra-hepatic cholangiocarcinoma harbouring an isocitrate dehydrogenase (IDH)-1 mutation and patients with fibroblast growth factor (FGFR) fusion- rearrangements. Identification of effective therapies in the advanced setting may, in turn, lead to improved adjuvant strategies. Finally, immunotherapy is emerging as an area of interest in cholangiocarcinoma based on the early findings from the KEYNOTE-28 study; future studies are planned to understand the additive/synergistic role with cisplatin/gemcitabine as well as translational studies aimed at identifying potential predictive factors for treatment efficacy. A challenge going forward is to navigate the demands for robust, practice-changing clinical data, in increasingly small sub-groups of patients in this relatively rare disease.