Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group Meeting

​The Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group hosted its much anticipated 3^rd Symposium of the Singapore Liver Cancer Consortium (SLCC) on 3 May 2019 at the Singapore National Eye Centre to a resounding success. 

In attendance were international members of the AHCC Trials Group, other HCC researchers, healthcare professionals and industry collaborators. As in the last two symposiums, the latest treatments in hepatocellular carcinoma (HCC) were presented and discussed as were developments in pre-clinical and clinical studies on HCC in the Asia–Pacific. 

Said Professor Pierce Chow, Senior Consultant, Division of Surgical Oncology, National Cancer Centre Singapore (NCCS): "In pursuance of our aims to bring about better clinical outcomes for patients with HCC, the AHCC Trials Group is constantly exploring collaborations with investigators from both academic research institutes and industry partners." 

The AHCC trials group has recently initiated 2 prospective studies on HCC in the Asia-Pacific (AHCC protocols 07 and 08). Prof Pierce Chow is the Protocol Chair of the AHCC Trials Group.

The Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group is a collaborative group formed in 1997 by clinicians treating HCC in major medical centres in the Asia-Pacific region. The aims of the trials group are to conduct preventive and therapeutic trials in HCC, to carry out basic and translational research in this field and to develop training and educational programmes pertaining to HCC. With these objectives, the trials group holds annual general meetings and symposia that bring together international experts to create opportunities to network and share updates and research ideas.

At the 3^rd symposium on 3 May 2019, local and overseas researchers on HCC including international key opinion leaders from Australia, Hong Kong and Japan presented treatment updates and early results of their studies.

Prof Chow summarized the progress of on-going studies conducted by the trials group namely, the TCR Flagship Program, Precision Medicine in Liver Cancer Asia-Pacific Network (the PLANet Study, AHCC07) and the HCC Registry in Asia (AHCC08). High intra-tumoral heterogeneity exists in HCC and the AHCC07 study is a multi-centre, prospective genomics-immunomics study that leverages on a surgical cohort for multi-region sampling of resected HCC. Patients are followed up to disease recurrence when recurrent HCC are similarly sampled and their genomic and immunomic profiles compared with that of the index resections to identify actionable biomarkers. 

A recent development has been the inclusion of a North American site at Duke Durham, which is expected to be initiated in Q3 this year. This new site will increase diversity and allow comparison of the genomic-immunomic profile of HCC in the Asia-Pacific with that of a separate population. The study has also expanded its scope (through successful grant applications), to include parallel epigenomic and metabolomic studies to further understand key mechanisms driving HCC.  

Separately the AHCC08 study is a multi-country prospective registry study of HCC patients from more than 30 sites in 9 countries of the Asia-Pacific. This registry will provide an insight into the different treatment journeys of HCC patients in Asia. To date, more than 1,500 patients have been recruited in the registry. Preliminary results have been presented in international conferences like ASCO GI 2019.

The symposium was attended by more than 120 attendees, including 30 overseas investigators. Members of the trials group had their general meeting in the afternoon of the same day. The next symposium and meeting will be next year. The AHCC Trials Group thanks all investigators and collaborators for their constant support over the last 22 years. 

The following presentations were made at the symposium. The AHCC Trials Group would like to thank all experts for sharing valuble insights and knowledge:

• Dr Naiyang Fu from the Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore shared his findings on an unexpected self-maintaining mode in hepatocyte regeneration and identified a defined subset of pericentral hepatocytes as major cells of origin in HCC development. Dr Fu's lab develops novel genetically engineered mouse models to study liver development, regeneration and cancer.
  

• Dr Glenn Bonney, a Consultant Liver, Pancreas and Transplant Surgeon at the National University Hospital (NUH) presented early results from a study he had initiated in cancer imaging of tumour/ normal boundaries in HCC using next generation mass spectrometry imaging. His latest findings suggest that there are molecular species that are uniquely and consistently expressed within the tumour margins of HCC. These consistent changes represent a paradigm shift and an opportunity for greater understanding in tumour biology, diagnostic and therapeutic targets. Dr Bonney has an avid interest in in using next generation proteomic platforms in real time to affect clinical and surgical endeavours.
  

• Prof Simone Strasser from the AW Morrow Gastroenterology and Liver Centre, the Australian National Liver Transplant Unit at Royal Prince Alfred Hospital (RPAH) and the University of Sydney presented the latest considerations in liver transplantation for NASH-related HCC.  She is also a steering committee member and a site investigator of the AHCC08 (HCC Registry in Asia) study.
  

• Prof Kudo Masatoshi, Chairman of the Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan, spoke on the evolving roles of targeted therapy in HCC. Systemic therapy for HCC has markedly advanced since the survival benefit of a molecular targeted agent, sorafenib, were demonstrated in the SHARP (Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol) and Asia Pacific trials in 2007. In the last 2 years, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) were positive in succession between 2017 and 2018, and FDA has approved the use of regorafenib, lenvatinib and cabozantinib in clinical practice. Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests that the treatment paradigm of HCC in all stages (early, intermediate and advanced), is expected to be changed drastically in the very near future.
  

• Dr Shin Yong Jae is the Chief Research Scientist of the Institute of Refractory Cancer Research (IRCR), Samsung Medical Center (SMC) and Research Professor at the School of Medicine, Sungkyunkwan University. He holds a joint appointment at NCCS as Deputy Director of the PuRPOSE Joint Laboratory Programme at A*STAR-IMCB. The PuRPOSE program aims to develop a personalized, targeted patient-specific diagnostic and predictive next-generation AVATAR system in HCC through multi-institutional collaborative efforts in Singapore. The platform provides reliable and patient-specific diagnostic and predictive data in a clinically relevant timeframe of three or four weeks. Patient-derived HCC tumor samples are leveraged upon for genomic correlation and for in vivo studies and drug screening. This platform is being validated to deliver precision analysis and revolutionise cancer treatment to improve clinical outcomes in patients with HCC.

• Dr Mihir Gandhi from the Singapore Clinical Research Institute (SCRI) applied his extensive experience in statistical and clinical research and in the planning and designing of phase I to III clinical trials, to the analysis of the Liver Cancer Registry (AHCC 08). He presented the initial data of the AHCC08 study which reveals considerable variation in presentation and management patterns in HCC between different countries in the Asia-Pacific namely China, Singapore, South Korea and Japan.
  

• Dr Thomas Yau, a well-known clinical researcher from the University of Hong Kong and Queen Mary Hospital, Hong Kong developed the Hong Kong Liver Cancer classification and is a global pioneer of a drug development program hepatocellular carcinoma. Dr Yau presented the latest developments in immunotherapy in HCC.
  

• Dr David Tai, a Senior Consultant, Division of Medical Oncology at NCCS, presented the updated analysis of an open label, single arm, phase 2 trial investigating the efficacy and safety of Radio-embolization with yttrium-90 combined with the immunotherapeutic nivolumab in HCC. Yttrium-90 radioembolization (RE) has emerged as an efficacious therapeutic option for intermediate stage hepatocellular carcinoma (HCC) while nivolumab, an anti-programmed death 1 (anti-PD1) monoclonal antibody, has been approved by FDA for use in the second line treatment of advanced HCC. Research in Singhealth has previously shown that RE significantly up-regulates systemic T cells and tumor-infiltrating lymphocytes and this was the basis of the hypothesis that the addition of nivolumab to RE will be synergistic.