APPLE conference 2016

Day 1 APPLE conference

Covered

HCC demographics: Over 900,000 deaths pa from HCC, 80% in Asia

Problem: Most cases secondary to Hep B or C so have poor liver function and co-morbidities, often not able to tolerate aggressive treatments. Even single tumors bigger then 2.5cm probably have several small satellites which have to be dealt with as well. Frequently there are multiple tumors in different segments.

Very heterogeneous bunch of tumors. Response to treatments very variable
Search for tumor markers to select patients suitable for different treatments

Screening & Surveillance: Japan appears to lead the pack in Asia. Most HCC the result of Hep C infections. Highly developed screening programme means they find the tumors when they are small and solitary and therefore treatable. Outcome best in Asia.

Immunotherapy: Check Point Inhibitors, Oncolytic Viruses have best potential.

Systemic: drugs blocking tumour growth factors, enhancing natural immune responses, cytotoxics

Improved Cytotoxic delivery: HAIC (Hepatic Arterial Infusion Chemotherapy), TACE (trans-arterial chemo-embolisation) and its cousin, DEB drug eluting bead embolisation

RFA (radio frequenecy ablation), Microwave Ablation, SBRT (Stereotactic body radiation)

SIRT (BTG and Sirtex). Impressive presentation. Downstaging prior to surgery, or given the right dose of radiation, capable of necrosing an entire segment or lobe, wiping out the tumor. Costs more than TACE, but seems better quality of life with fewer side effects.

Surgery: Professor Ronald Poon clearly the star presentation of the day. Showcase of humble but exceptional skill and expertise showing how far surgical intervention has come in 10 years. Basically can offer the chance of cure in even extreme cases. If the patient has 25% functional liver, can divide off the good 25% and ligate the portal vein allowing that 25% to hypertrophy to 33% in around 10 days. Then come back and resect the diseased part. Satellite tumor in the good lobe? Insert a probe during the operation and necrose it with RFA. Tumour occluding the Inferior Vena Cava or Portal Vein? Resect it and put in a graft!! 1% mortality, less than 5% need blood transfusion, progression free survival rivals any other treatments and as a bonus an overall 5% chance of cure. No other treatment really can offer that. Just incredible skills. Clearly the first option before considering the rest.

Surprising lack of evidence behind the treatment protocols. TACE for instance failed to show improvement over Best Supportive Care in 5 out of 7 studies, but appears to have been adopted as standard first line treatment where surgery is contra-indicated for 20 years. Even the choice of drugs being used in TACE is really just the preference of the oncologist. Choices are often driven by financial considerations eg goverments subsidy or medical insurance cover.

My impression is the field is potentially wide open and SIRT has very good potential. Maybe Theraspheres work as well as Sirspheres but the market is huge. The first hurdle is to provide hard evidence that SIRT itself can be accepted as an option for first line therapy either where surgery is contra-indicated, or to down grade the cancer and allow hypertrophy of the remaining liver as a prelude to curative surgery.

My assessment in regard to SIRT: Very encouraging. I am not selling my shares. Sirtex presentation tomorrow. BTW, David Cade is on holiday so not in attendance.