ILCA Special Interest Groups (SIGs) Luncheon Workshops

12:45 — 14:00 Saturday, 5 September 2015

SIG 1: Molecular Classification and Signalling Pathways
Animal Models Relevant to Human Liver Cancer

Chairs: Xin Wei Wang, PhD (USA) and Wen Xue, PhD (USA)

The cancer genome is highly complex, with hundreds of point mutations, translocations, and chromosome gains and losses per tumour. Likewise, the clinical presentation of hepatocellular carcinoma (HCC), a major type of primary liver cancer, is highly heterogeneous. Its diagnostic, prognostic and treatment assessment is often complicated by both tumour biology and compromised liver function due to underlying chronic inflammatory liver diseases such as fibrosis and cirrhosis. To understand the effects of various cancer genes, precise models that incorporate both genomic changes in tumour cells and appropriate hepatic microenvironmental milieu are needed.

However, the presence of considerable genomic alterations constitutes a bottleneck and poses an enormous challenge to effectively rank, triage and evaluate these candidate driver genes as druggable targets. While mouse tumour models are powerful tools to study cancer biology and to facilitate bench-to-bedside research, mouse livers are highly sensitive to neoplastic transformation. Consequently, numerous genetically-modified mouse models for HCC are currently available. A critical question remains as to which mouse models are most relevant to human HCC. In this workshop, we will describe approaches to the construction and utility of various mouse models of human liver cancer, including germline, somatic and ex vivo models. The recent development of the CRISPR-Cas9 system, a powerful genome-editing tool for efficient and precise genome engineering, is transforming mousemodel generation. We will describe how CRISPR-Cas9 has been used to create mouse models of liver cancer with point mutations, deletions and complex chromosomal rearrangements. We will highlight the progress and challenges of such approaches, and how these models can be used to understand progression of liver tumours and to identify new strategies for cancer treatment. The generation of precision liver cancer mouse models will provide a rapid avenue for functional cancer genomics and pave the way for precision cancer medicine.

Topic outline

  1. The need for precision cancer models
  2. Traditional mouse model of liver cancer
    • – Chemical-induced
    • – Germline mouse models: transgenic, knockout, etc.
    • – Somatic mouse models: hydrodynamic system
    • – Ex vivo: embryonic liver progenitor cell transplant
    • – CRISPR mouse models
    • – Engineering structural variations
  3. Generating mouse model through the CRISPR system
  4. Challenges

12:00 — 14:00 Saturday, 5 September 2015

SIG 2: Surveillance, Biomarkers and Molecular Pathology
HCC Early Detection

Chairs: Amit Singal, MD (USA) and Massimo G. Colombo, MD (Italy)

Several societies, including the AASLD, EASL and APASL recommended HCC surveillance in patients with cirrhosis to improve early tumour detection and overall survival. Although a randomized trial in China demonstrated HCC surveillance significantly lowered annual mortality rates in patients with chronic HBV infection, there is no similar Level I evidence supporting HCC surveillance among patients with cirrhosis. Prior attempts to obtain randomized data failed due to poor patient enrollment, and the authors concluded a randomized trial in patients with cirrhosis might not be feasible. Data from HBV-infected patients cannot be extrapolated to those with cirrhosis due to lower sensitivity of ultrasound with a nodular liver, reduced eligibility for curative treatments such as resection, and higher competing risk of non-HCC mortality. HCC surveillance in patients with cirrhosis is supported by several cohort and case-control studies; however, two recent meta-analyses concluded higher quality data are needed given methodological limitations of current data including lead-time bias, length-time bias, and inadequate follow-up duration. Lack of high quality Level I data has led some providers to question the merits of HCC surveillance, contributing to underuse of HCC surveillance in clinical practice. In this luncheon workshop, Drs. Colombo and Singal will discuss current data evaluating HCC surveillance in patients with cirrhosis, areas of need for higher quality data, and the potential necessity/feasibility of obtaining Level I data.

12:45 — 14:00 Saturday, 5 September 2015

SIG 3: Imaging and Loco-Regional Therapies
Standardising TACE – Defining TACE Failure

Chairs: Riad Salem, MD (USA), Riccardo Lencioni, MD (Italy), Yasuaki Arai, MD (Japan)

Transarterial chemoembolization (TACE) is used for the treatment of hepatocellular carcinoma not amenable for resection or percutaneous ablation. TACE embraces different procedures that aim at inducing ischemic necrosis and increasing the exposure of tumour cells to cytotoxic agents. In conventional TACE this is accomplished by the sequential intra-arterial injection of chemotherapeutic agents mixed with Lipiodol and embolizing particles. Despite the efforts of scientific societies to standardize TACE procedures, there are worldwide variations of drug vehicles, cytotoxic agents and embolizing particles, angiographic endpoints and selectivity. Superselective catheterization and the use of calibrated particles (including cytotoxic drugeluting beads) should be preferred. Repeating TACE ‘on demand’ depending on the observed response and not at fixed pre-planned intervals is recommended nowadays because of the lower toxicity associated with this approach.

Tumour response after conventional or DEB-TACE should be evaluated using EASL or modified RECIST criteria that take into account tumour shrinkage and tumour necrosis. In patients with no tumour, response to the first TACE sessions should be considered for treatment with radioembolization or the systemic agent Sorafenib. Decision algorithms based on scores that take into account changes in liver function, levels of transaminases and tumour response should be validated prospectively before they can be recommended for clinical use.

12:45 — 14:00 Saturday, 5 September 2015

SIG 4: Target and Systemic Therapies
Hepatocellular Carcinoma with Stem Cell Features: How Can We Define and Handle Them

Chairs: Joong-Won Park, MD, PhD (Republic of Korea) and Tim Meyer, MD, PhD (United Kingdom)

Hepatocellular carcinoma (HCC) has proved relatively refractory to systemic therapy, which has been associated with a low response rate and marginal improvement in survival. The existence of hepatocellular cancer stem cells (CSC) has been proposed as one of the mechanisms of resistance and the identification and therapeutic targeting of this sub-population has been the subject of intense research. Current data suggest that the co-expression of markers such as EpCAM and AFP define a Hepatic CSC phenotype with the ability to self-renew, differentiate and initiate tumours. Key signalling pathways that are dysregulated include the Wnt/beta-catenin, AKT, TGF-β pathways but the challenge for therapeutic targeting is to differentiate Hepatic CSC from normal hepatic SC. A number of strategies based on inhibition of NF-kB, microRNAs and epigenetics have been proposed and clinical trials are ongoing. Aim of the session is to address the following questions:

  1. Introduction – Cancer stem cells in HCC: theory, evidence, and definition
  2. Clinical meaning of primary liver cancer with CSC
  3. Clinical perspectives in diagnosis of HCC CSC: pathologic and radiologic views
  4. How can HCC CSC be targeted for therapy?
  5. Discussion and wrap-up

12:45 — 14:00 Saturday, 5 September 2015

SIG 5: Liver Surgery and Transplantation
Surgery and Transplantation

Chairs: Thomas Decaens, MD, PhD (France) and Katsuhiko Yanaga, MD, PhD (Japan)

Liver surgery (resection and transplantation) remains the best therapeutic option for hepatocellular carcinoma (HCC). Both treatment are associated with very good 5-year overall survival despite a huge difference in tumour recurrence rate.

European, American and Asian guidelines are restricting the use of liver resection and liver transplantation to some patients. However, recent studies are showing good results in extended criteria such as resection in portal hypertension patients, resection in case of portal invasion, liver transplantation with extended criteria, liver transplantation after down-staging. During this luncheon, we will present these new data and discuss with the audience about perspectives.

12:45 — 14:00 Saturday, 5 September 2015

SIG 6: Non-HCC Hepatic Malignancies
Update Systemic Therapy

Chairs: Shahid A. Khan, MD, PhD (United Kingdom) and Gregory J. Gores, MD (USA)

This workshop will begin with two short presentations, each of 15-20 minutes, followed by an open discussion and Q&A session.

Professor Gores will explore recent advances in our understanding of the aetiopathogenesis of cholangiocarcinoma. He will cover risk factors (obesity, hepatitis C virus, primary sclerosing cholangitis); the diagnosis of CCA in patients with PSC; and oncogenic pathways such as IDH and FGFR fusions and their therapeutic indications.

Dr. Khan will then summarise the currently available non-surgical therapies for cholangiocarcinoma, including locoregional treatments, and provide an update on systemic therapies. The focus will be on the therapeutic potential of targeting specific molecular pathways.

12:45 — 14:00 Saturday, 5 September 2015

Egypt Meets ILCA
Common Approaches and Regional Disparities

Chairs: Peter R. Galle, MD, PhD (Germany) and Mahmoud El Meteini, MD (Egypt)

HCC is the most deadly complication of chronic liver diseases and emerged into a substantial healthcare problem in both Western countries as well as Africa, including Egypt. A striking variation in epidemiological factors of HCC divides Egypt from the Western world, whereby complex etiological differences are mainly related to the prevalence of major associated risk factors. While HCV is the most important risk factor for the development of HCC in Egypt, alcohol intake and NASH are predominant in the western world. Over the recent years, stabilization of incidence rates were observed in the Western world. However, a continuous incline is documented in Egypt and predicted to peak within the next 10-20 years. Therefore, detailed characterization, collection of patient data as well as scientific analysis of common and distinct features of HCCs in the different regions are of utmost importance to foster global approaches for preventive, diagnostic and therapeutic strategies and to optimize patient management.

The session will give an overview about common standards and distinct approaches between Egypt and Western countries. In particular, therapeutic approaches including surgery and loco-regional strategies will be discussed. In this context, the potential impact of new HCV treatment regimens for future HCC therapies will also be delineated. The overall goal is to define regions of common interest and to foster new collaborative clinical and scientific collaborations to overcome the current era of unmet therapeutic needs in HCC.

Epidemiology of HCC and Hepatitis C: Egyptian Experience
Mohamed Kamal Shaker, MD (Egypt)
Treatment
Ashraf Omar, MD (Egypt)
Clinical Trials
Marcus-Alexander Wörns, MD (Germany)
Research
Jens U. Marquardt, MD (Germany)