12:45 – 14:00 Saturday, 14 September 2013

Luncheon Workshop 1: Primary and Secondary Prevention of HCC
Chairs: Massimo G. Colombo, MD (Italy), Amit Singal, MD (USA)

Hepatocellular carcinoma (HCC) develops in the context of readily identifiable risk factors, enabling successful primary and secondary prevention strategies. Primary prevention refers to modification of potential etiologic factors, whereas secondary prevention refers to identification and treatment of pre-neoplastic and/or early neoplastic lesions. Given the primary risk factors for hepatocellular carcinoma (HCC) are hepatitis B (HBV) worldwide and hepatitis C (HCV) in developed countries, most data on primary prevention has focused on vaccines and anti-viral therapy. Universal HBV accination of newborns in Taiwan has been associated with a steady decline in annual HCC incidence rates. Similarly, viral suppression with nucleos(t)ide analogues in HBV patients and a sustained virological response in HCV patients may counteract the risk of neoplastic transformation of the liver. Less robust data exists on HCC prevention through modification of other known risk factors, such as alcohol cessation, weight loss, and control of diabetes.

Secondary prevention depends upon detection of tumours at an early stage, when curative options exist. Secondary prevention by screening aimed to detect early HCC is worthwhile in selected populations like hepatitis C patients with ≥ 1.5% incidence of HCC, hepatitis B patients with > 0.2% incidence and, in general, patients with cirrhosis with > 2.5% incidence. Current guidelines recommend surveillance using ultrasound alone every 6 months, although AFP may be of incremental benefit in clinical practice. A large RCT from China demonstrated HCC surveillance improves overall survival in patients with chronic HBV infection. Although there is not a RCT in patients with cirrhosis, several cohort studies have demonstrated patients undergoing surveillance are significantly more likely to be detected at an early stage, undergo curative treatment, and have longer survival than those not undergoing surveillance. The recall policy in those with a positive surveillance test includes contrast-enhanced CT scan, MRI, or liver biopsy.Overall, HCC prevention is an important aspect in the care of patients with chronic liver disease.

12:45 – 14:00 Saturday, 14 September 2013

Luncheon Workshop 2: Differences in Treatment Algorithms in East and West
Chairs: Kwang-Hyub Han, MD (South Korea), Morris Sherman, MD, PhD (Canada) and Norihiro Kokudo (Japan)

There have been a number of treatment algorithms for HCC. They are based on available evidence from the literature and current daily practice and consensus among physician in each region. This workshop will overview HCC treatment algorithms worldwide and discuss what is universal and what is different among them. Prof. Sherman is going introduce BCLC guidelines and updated modifications in North America and Prof. Han and Prof. Kokudo will introduce guidelines in eastern countries.

12:45 – 14:00 Saturday, 14 September 2013

Luncheon Workshop 3: Treatments before and after Transplantation
Chairs: Thomas Decaens MD, PhD (France), Bruno Sangro, MD, PhD (Spain)

Liver transplantation (LT) remains the best therapeutic option for hepatocellular carcinoma (HCC). Indications of LT for HCC are restricted by criteria which allow 5-year overall survival of 65-80% and 5-year recurrence rate of 8-12%. Due to the limited availability of liver donors, there is a need to develop therapies that may help reducing this rate and increasing survival.

Most centers use neoadjuvant therapies (particularly local ablation and transarterial therapies) to prevent tumour progression while patients wait for LT, although the scientific evidence that supports this practice is weak. We will thus discuss the impact of neadjuvant therapy on post-LT outcomes.

On the other hand, level 2 evidence suggests that LT after stable downstaging to Milan criteria results in adequate survival outcomes, probably by allowing some tumours to show their more indolent behavior in a test of time.

This risk of post-LT recurrence depends on several factors, few of them accessible to intervention. Interferon and adoptive immunotherapy have shown positive signals in the prevention of recurrence after liver resection of HCC but stimulating the immune system carry specific risks in transplanted patients. We will discuss how to better manage patients with high risk of tumour recurrence including the widespread use of immunosuppressive regimes based on an m-TOR inhibitor.

Finally, if relapse occurs, the general therapeutic paradigm should still be considered including resection or ablation, transarterial techniques and sorafenib, which safety profile is similar in transplanted and non-transplanted patients HCC.

12:45 – 14:00 Saturday, 14 September 2013

Luncheon Workshop 4: TACE vs Y-90 in Intermediate HCC
Chairs: Jean-François Geschwind, MD (USA), Riad Salem, MD (USA)

Chemoembolization represents the mainstay of treatment for patients with intermediate disease. This is based on 2 RCTs demonstrating an improvement in survival when compared with best supportive care. Radioembolization represents an alternate transarterial treatment with fewer toxicities and improved quality of life when compared to TACE in prospective studies. This lunch symposium will discuss the 2 transarterial treatment modalities and highlight the most recent data.

12:45 – 14:00 Saturday, 14 September 2013

Luncheon Workshop 5: Signaling Pathways and Emerging Therapies in Advanced HCC
Chairs: Sandrine Faivre, MD, PhD (France), Ann-Lii Cheng, MD, PhD (Taiwan)

Beyond tyrosine kinase inhibitors, little progresses have been made with targeted therapies for HCC in the past six years. Acquired resistance to VEGFR/PDGFR inhibitors has been associated with various aspects of epithelialto-mesenchymal transition; MET/HGF, TGF-beta, and CXR4/SDF-1(CXCL12) overexpression; facilitating cellular invasion and occurrence of metastases. Upcoming challenges in HCC rely in (1) identifying novel drugable targets associated with poor prognosis HCC and (2) revealing drug-accessible pathways that appear in tumours primed by prior sorafenib exposure.

Promising results were recently obtained with MET-inhibitors in patients with HCC showing high MET expression, and TGFbeta receptors that are activated in poorly differentiated HCC might be inhibited with compounds such as the TGFbetaR1 inhibitor LY2157299 which displays a good safety profile. Chemokine receptors coupled to G-protein, including CXCR4, have been reported in preclinical models of HCC developing acquired resistance to VEGFR inhibitors, yielding to explore CXCR4 inhibitors in advanced HCC. Oncolytic virotherapy and immunotherapy such as lenalidomide, anti-CTLA4, and anti-PD1 are other approaches in development.

Driving drug development toward those novel targets remains a challenge requiring the use of tumour biomarkers and novel imaging techniques. Designing original clinical trials shall also be considered to reveal the potential of those novel drugs either as single agents or in combination with sorafenib.