Scientific Programme
The programme of the Summit showcased the most recent advances in the understanding of the pathogenesis of the two most common primary liver malignancies – hepatocellular and cholangiocellular carcinoma – and debated the state-of-the art in the diagnosis and treatment of patients affected by these primary liver tumours.
The three day EASL Liver Cancer Summit 2024 included a full scientific programme:
- 11 scientific sessions
- 8 ePoster sessions
- 2 State-of-the-Art sessions
- 2,5 days of scientific content
- 37 faculty from 10 countries
Session 1 - Molecules and mechanisms in liver carcinogenesis: an update
Our understanding of the molecular mechanisms of liver cancer development and progression is still far from satisfactory. The complex interactions among mutant oncogenic pathways, and the additional layers of complexity added by alterations in chromatin regulatory mechanisms draw an intricate landscape. This session will showcase the most relevant and recent advances in the fundamental understanding of HCC and CCAs molecular biology; from driver mutations, epigenetic alterations, and regulatory RNAs to the analysis of the cancer proteome. Potential new therapeutic targets will be highlighted.
Learning objectives:
- Learning about the most updated mutational portraits of HCC and CCAs.
- Gaining an overview of our current understanding of epigenetic dysregulation in liver tumors: its critical role and druggability.
- Discovering the broad family of non-coding RNAs and their multifarious roles in carcinogenesis.
- Getting a grip on the latest developments in liver cancer proteomics and its potential to unravel the biology of hepatobiliary tumors.
Session 2 - New approaches for the study of liver cancer pathogenesis and target identification
The study of complex diseases like cancer requires the swift implementation of all available multidisciplinary techniques. In this session three rapidly growing areas that provide complementary insights will be covered. Metabolomics, the oldest among the “omics” technologies, is currently attracting significant attention. The realization of the strong interactions between metabolic alterations and carcinogenesis, see for instance the crosstalk between the metabolome and epigenetic mechanisms, together with the importance of identifying new biomarkers of the disease, explain this renewed interest. Digital pathology, sitting at the confluence of digital imaging technologies, network-based exchange of information, and the application of artificial intelligence in medical imaging will benefit not only diagnosis but a better understanding of disease mechanisms. The latest developments in functional and molecular imaging, which are also game changers in early cancer detection, biomarker discovery and monitoring the efficacy of targeted therapies, among other applications, will also be highlighted.
Learning objectives
- Discovering the latest technological developments in metabolomic analyses.
- Learning about the critical interface between metabolites and tumorigenic mechanisms.
- Understanding the foundations of digital pathology, along with its perceived advances and limitations.
- Gaining insight into the wealth of information that functional imaging can provide on different aspects such as tumor biology, behavior and treatment response.
Session 3 - Screening HCC and biliary tract cancer: who and how?
Chronic liver disease predisposes to HCC and BTC and the prevention of chronic liver disease therefore reduces the population at risk. The impact of this approach has been clearly demonstrated in Taiwan where the introduction of a national hepatitis B vaccination program for newborns in 1984 resulted reduction in the incidence of HCC in those aged under 30. Meanwhile, ALD and MASLD are emerging as the dominant risk factors for liver cancer in the West, and public health measure are urgently needed to react to this epidemiologic transition. There are, however, few data to support the efficacy of surveillance for HCC or BTC in these patients. International guidelines recommend HCC surveillance of high-risk populations with six monthly abdominal ultrasound with or without Alpha-fetoprotein (AFP). Patients with primary sclerosing cholangitis (PSC) in Western countries are at increased risk of CCA and Guidelines for surveillance of these patients are available. In this session, current recommendation for HCC and BTC surveillance will be summarized and discussed.
Learning objectives
- Gaining insight into the recent recommendations for surveillance in liver cancer
- Understanding the challenges and opportunities for surveillance in HCC and BTC
State-of-the-Art 1: The tumor immune environment in liver cancer
Despite recent success in cancer immunotherapies, the complex dynamics within tumor-immune microenvironment (TIME) remain elusive. With the multidimensional analysis pipeline, we have successfully identified and described key immunological factors in hepatocellular carcinoma (HCC) that contribute to disease progression and clinical response to therapy. Our findings include the discovery of immunological biomarkers for predicting therapeutic outcomes in HCC patients, providing valuable insights to inform the design of novel and more effective therapeutic strategies.
Session 4 - Advances in diagnosis of liver tumors
Session 5 - Liver tumors pathology: from tissues to algorithms
In the era of precision medicine one key aspect is the availability of metrics that can inform on the molecular and cellular characteristics of early tumoral lesions, and also predict the clinical evolution of those already diagnosed. These biomarkers can be integrated together with additional cellular and molecular features that may inform on the potential response of tumors to targeted therapies, as in the case of some types of CCA, or ICI-based in HCC. Although encouraging, the success of precision approaches to treatment have been mixed in different types of tumors, and the field is incipient in liver cancers. On the other hand, multiple technologies to detect molecular variations are available, but the costs are still high in many cases. Also, multiplex testing of alterations beyond mutations may need to be integrated to predict response to paired agents. All these issues will be dealt with in this short but tantalizing session.
Learning objectives
- Learning about the latest developments in the identification and validation of histopathological biomarkers predicting patients’ prognosis.
- Finding out about the most recent methodological advances in the histological analysis of liver tumors.
- Reviewing the available and upcoming technologies in the molecular analysis of liver tumors and their interpretation in clinical practice.
- Understanding the current challenges and limitations of personalized medicine in patients with hepatobiliary tumors
Session 6 - Update in systemic therapies for hepatocellular carcinoma
Systemic therapy is the preferred treatment modality in the advanced stage and in intermediate stage patients who do not qualify for local therapies. Survival of patients treated with systemic agents has significantly improved over time and with the approval of six treatment regimens by EMA and 8 regimens by FDA sequential therapy can now be routinely considered for patients with advanced HCC. The efficacy of ICI based combinations provide a rationale to evaluate their role in earlier stages.
The selection of systemic therapy for an individual patient will be influenced by several factors including efficacy and toxicity, and the presence of contraindications or predictive factors. For most patients, combination therapy including a PD1/PD-L1 inhibitor will represent the first-line treatment of choice. In the second-line setting, the only evidence-based sequences are for regorafenib, cabozantinib or ramucirumab following 1st sorafenib. There are no meaningful differences in efficacy for any of these drugs evaluated in the 2nd setting and the best treatment sequences of the available drugs have not been established.
Learning objectives
- Understand endpoints in clinical trials and its implication for daily decision making.
- Learning about the latest developments in the systemic therapies in early and advanced stage HCC.
- Finding out about the most recent criteria for selection of systemic therapies
- Gaining insight in clinical and molecular biomarkers for systemic therapies
Session 7 - Experimental models in liver cancers and translational challenges
A central aspect in the elucidation of carcinogenic mechanisms is their evaluation in in vivo models that reproduce the natural history of the human disease. Albeit the information gathered in this context is valuable, interspecies differences may lead to conclusions not relevant to the human disease. This caveat also applies to the evaluation of the efficacy of new therapeutic strategies. In this ample session cutting-edge in vitro, ex vivo and in vivo experimental models of liver tumors will be presented. Their advantages, complementarities and limitations in fundamental research, as well as in drug development, will be discussed.
Learning objectives
- Understanding the methodology behind the development of organoids and tumoroids and their potential applications in liver cancer research and treatment.
- Gaining insights into the translational relevance of precision cut liver slices as models of human liver disease and cancer.
- Learning about the latest developments in patients’ derived xenograft models, their usefulness and limitations.
- Discovering what preclinical models can, and cannot, tell about the safety and efficacy of therapies when tested in humans.
Session 8 - Update in systemic therapies for biliary tract cancer
The prognosis of patients with biliary tumors is still very poor. However, after many years of stagnation, there has been an expansion of therapeutic options in systemic therapy in recent years: on the one hand, immuno-oncology has become part of the standard of care in the first line, and on the other hand, studies in genetically selected subgroups have shown the potential of targeted strategies. Nearly 40% of patients with BTC harbour genetic alterations, which are potential targets for precision medicine. Therefore, molecular analysis should be carried out before or during first-line therapy to evaluate options for second and higher lines of treatment as early as possible in advanced disease.
Learning objectives
- Understanding the role of immune- and molecular therapies in BTC
- Gaining insights into opportunities and challenges with targeted therapies in BTC
- Learning about clinical and molecular biomarkers for treatment selection
- Discovering what is known about resistance to targeted and immunotherapies
State of the art 2: Re-thinking the limits of liver transplantation in liver cancer
Liver transplantation represents the best treatment option for HCC. In this lecture, Dr. Sapisochin will be summarizing the most updated data on liver transplantation for cancer. In recent years, thanks to better understanding of liver cancer biology and improvements in therapies, liver transplantation is being offered to patients with liver cancer (HCC or iCCA) that were not candidates in the past. The concept of size and number as a single criteria to select candidates seems updated and new criteria are being proposed. He will also be giving some insight into the future of liver transplantation for liver cancer and were the limits may be.
Session 9 - Tumor microenvironment and immune landscape: mechanisms and therapeutic opportunities
While mutations are key driving forces, a variety of signals coming from the microenvironment also play a central role in liver carcinogenesis. This multitude of signals of different chemical nature and cellular origin may come from distant tissues, such as the gut, but can also be generated by the fibrogenic stroma, as well as resident or recruited immune cells. Understanding how this intricate microenvironment fosters carcinogenesis, shapes the behaviour of tumoral and immune cells, and conditions the response to therapy, mainly of immune-based strategies, are fundamental issues that will be discussed in this session.
Learning objectives
- Learning about the relevance of immune mechanisms involving the gut-liver axis in liver tumor development.
- Understanding the differential mechanisms leading to HCC in the context of MASLD.
- Discovering the key forces from the fibrogenic stroma that drive hepatobiliary carcinogenesis.
- Getting a grip on the emerging strategies to enhance the efficacy of immune-based therapies in HCC.
Session 11 - Treatment of liver cancer in patients with impaired liver function
Tumour stage at diagnosis is associated with overall survival (OS), and presence (and extent) of any underlying liver disease is an important clinical consideration when treating patients with HCC. Most patients with HCC have some degree of underlying liver fibrosis (usually at the stage of cirrhosis), and the extent of liver dysfunction has an impact on disease prognosis and treatment selection. To assess liver function, several liver function scoring systems have been developed, including the Child-Pugh score (CPS), and albumin-bilirubin (ALBI) grade. Almost all treatment option have only been evaluated in patients with well compensated liver function, and there is high unmet need for patients with CP B cirrhosis.
Learning objectives
- Understanding the how liver function impact prognosis in hCC.
- Gaining insights into methods to assess liver function.
- Learning about who different treatments can impact liver function.
- Discovering what options are available for patients with impaired liver function.
Session 10 - Multidisplinary treatment approaches for hepatocellular carcinoma and biliary tract cancer
To ensure that the individual patient is matched with the optimal therapy, clinical decision making in liver cancer patients requires a multidisciplinary team, that longitudinally re-evaluates and adapts therapeutic strategies. While local therapies remain the mainstay of early disease stages in BTC and HCC, there is currently a paradigm shift in patients with intermediate HCC. In light of the significant progress in the systemic treatments, a critical review of the indication for locoregional therapies is mandatory. Apart from the identification of the optimal candidates for local therapies, the appropriate time to transition from local to systemic therapies must not be missed. Due to the frequent occurrence of liver-only disease in BTC, which might have a better prognosis compared with all patients with advanced BTC, locoregional treatment has been increasingly studied, including local ablation and intra-aterial therapies. In case of response following locoregional or systemic treatment of locally advanced HCC and BTC, patients should be re-assessed by the MDT to discuss the potential use of local therapies.
Learning objectives
- Understanding the role of the MTD in the management of liver cancer.
- Gaining insights into the criteria for selection criteria for local therapies.
- Learning about sequential therapies in clinical practice.