12:45 — 14:00 Saturday, 6 September 2014

Luncheon Workshop 1: Current Issues on Tumour Genomic Heterogeneity and its Implication in Clinical Practice
Chairs: Jessica Zucman-Rossi, MD, PhD (France), Xin Wei Wang, PhD (USA) and Jens U. Marquardt, MD (Germany)

Similar to other lethal solid tumours, a majority of hepatocellular carcinoma and cholangiocarcinoma are clinically and biologically heterogeneous, and do not respond to treatment well. Patient ethnicity, underlying liver diseases due to various etiological factors such as viral hepatitis, parasitic infection, alcoholic liver disease, or obesity, etc., may contribute to both inter-tumour and intra-tumour genomic heterogeneity.

In addition, hepatic microenvironment due to various degrees of liver fibrosis and cirrhosis, may affect tumour biology. Tumour heterogeneity is a timely subject for discussion as it is the main factor to impede treatment options and to pose a significant challenge to cancer management. The main objective of this workshop is to summarise current knowledge about liver cancer heterogeneity, to discuss hypotheses and potential molecular mechanisms, and to propose options to overcome this challenge.

12:45 — 14:00 Saturday, 6 September 2014

Luncheon Workshop 2: Immune-Pathogenesis of HCC and Therapeutic Implications
Chairs: Tim Greten, MD (USA) and Robert Wiltrout, PhD (USA)

Sustained chronic hepatic inflammation, driven by alcohol consumption, non-alcoholic fatty liver disease, and/or chronic viral hepatitis (hepatitis B and C), results in damage to parenchyma, oxidative stress, and compensatory regeneration/proliferation in the liver. There is substantial evidence linking these inflammation-associated events with the increased incidence of hepatocellular carcinogenesis. In contrast, immune based-therapies targeting specific immunological events leading to activation of anti-tumour immunity represent an increased area of interest in hepato-oncology.

We will review and discuss current concepts of immune mediated hepato-carcinogenesis with a specific focus to better understand how immune responses accelerate hepato-carcinogenesis in clinically relevant mouse models as well as in patients with different types of chronic liver diseases. Based on these findings we will try to develop new therapeutic concepts aiming at prevention of immune mediated tumour development. In order to design new treatment paradigms for patients with HCC, we will review how currently used non-immunological treatment methods affect immune responses and how those treatments can be potentially used synergistically with novel immune-based treatments in oncology to develop novel and better concepts in the treatment of patients with HCC.

12:45 — 14:00 Saturday, 6 September 2014

Luncheon Workshop 3: Transarterial Treatment of HCC – Differences and Similarities: North America vs. Europe vs. Asia
Chairs: Riad Salem, MD (USA), Riccardo Lencioni, MD (Italy), Yasuaki Arai, MD (Japan)

TACE is the most widely used treatment for HCC patients unsuitable for radical therapies worldwide. The data collected in the GIDEON, the largest global observational study completed in the field of HCC clinical management so far, suggests that nearly half of all HCC patients receive TACE at some timepoint in the course of the disease. Conventional TACE regimens are based on the administration of an anticancer-in-oil emulsion followed by embolic agents. The key component of this procedure is Lipiodol, which is used both as a vehicle to carry and localise the chemotherapeutic agent inside the tumour and as a microembolic agent for tiny tumour vessels. Randomised controlled trials (RCTs) and meta-analyses have shown that TACE improves survival with respect to best supportive care. As a result, TACE has been recommended by most guidelines as the standard of care for the treatment of unresectable, large or multinodular noninvasive tumours isolated to the liver, in patients who have neither evidence of hepatic decompensation nor cancer-related symptoms. Overall, TACE is expected to improve the median survival of such patients at the intermediate stage of the BCLC classification from around 16 months to about 19-20 months. However, RCTs comparing TACE and best supportive care were performed more than a decade ago. Distinct technical advances in the performance of TACE took place since the completion of these studies, including the introduction of super-selective arterial approaches by using micro-catheter systems and the use of angio-CT/ cone-beam CT to improve the accuracy in identifying tumour-feeding vessels and the ability to confirm adequate targeting and saturation of the tumour. In a recent prospective study conducted in Japan and South Korea, median survival of TACE-treated patients was 3.1 years. Understanding the current survival figures achieved by TACE in patients with HCC is crucial, given that several alternate treatment options have become available. In fact, various strategies to improve outcomes for this patient group have become the subject of much ongoing clinical research. Embolic, drug-eluting beads for transarterial administration have been shown to reduce liver toxicity and systemic drug exposure compared to standard TACE and are currently used as an alternative TACE regimen especially in Europe and in the US. Radioembolisation with Y90 is challenging the current paradigm of HCC treatment. Multiple centers around the world have provided compelling data that suggest a clinical role in patients with portal vein thrombosis as well as in downstaging to transplantation or conversion of surgically inoperable patients (due to small liver remnant) to potential cure with resection. The next few years will yield important information as results from the on-going phase 3 RCTs further define the role of the novel transarterial treatments in HCC clinical management.

12:45 — 14:00 Saturday, 6 September 2014

Luncheon Workshop 4: Systemic Therapy for HCC – Why Do We Keep Failing?
Chairs: Richard Finn, MD (USA), Tim Meyer, MD, PhD (United Kingdom) and Joong-Won Park, MD, PhD (South Korea)

The publication of the SHARP and Asia Pacific trials established Sorafenib as the standard of care for advanced HCC and heralded a new era of drug development for this previously refractory disease. Seven years on, after numerous trials, sorafenib remains the only drug approved for first line therapy and there is no proven second line or adjuvant systemic therapy. During this period we have learned that response rate, time to progression and progression free survival in phase II trials are not reliable indicators of survival benefit in phase III trials and that phase III trial design needs very careful consideration. Concurrently, we have witnessed significant progress in other tumour types where molecular targeted therapy is increasingly stratified according to relevant oncogenic drivers and new approaches including immunotherapy are transforming outcomes in lung cancer and melanoma respectively. Lessons need to be learned both from the recent failures in HCC and from the successes in other tumours. We now understand much more about the key molecular drivers of hepatocellular oncogenesis and this will permit the development of a more rational and stratified approach. While this presents opportunities, it also presents significant challenges since many genetic alterations are not currently amenable to pharmacological manipulation and others are rare, mandating significant pre-screening and additional expense. Immunotherapy and rational combination therapies are also being actively explored and there is reason for renewed but cautions optimism. In this workshop we will review the existing data in HCC drug development and offer insight into how to avoid failures in the future. The audience will be asked to participate in the discussion as well.

12:45 — 14:00 Saturday, 6 September 2014

Luncheon Workshop 5: Liver Transplantation for Cholangiocarcinoma: Where do we Stand and Future Directions
Chairs: Pierre-Alain Clavien, MD, PhD (Switzerland), Shahid A. Khan, MD, PhD (United Kingdom)

This workshop will begin with two short presentations, each of 10-15 minutes, followed by an open discussion and Q&A session. Dr. Khan will summarise the history of liver transplantation for Cholangiocarcinoma and explain why it has been a relative if not absolute contraindication in most centres worldwide. He will also summarise the recent epidemiology, risk factors and currently utilised available therapies for cholangiocarcinoma, including surgical resection, locoregional therapy (raditation, TACE, TACI, TARE), radiofrequency ablation and systemic chemotherapy. Prof. Clavien will then review the more recent data on liver transplantation for Cholangiocarcinoma as well as the newly established staging system.