Dr Peppy Brock is a retired consultant paediatric oncologist. She explains how a dedicated international group of medical professionals helped improve survival and reduce toxicity for a very rare type of childhood cancer.
There are around 20 cases of liver cancer in children per year in the UK, the commonest type being hepatoblastoma (HB), localised to the liver. Children with localised HB have an average age of 13 months at diagnosis. Even though this cancer is rare, the rate of children now surviving this type of cancer is greater than 90% compared to around 30% during the 1970s. This is the result of international collaboration, clinical trials and knowledge-sharing over many years through an expert group called SIOPEL.
I was lucky enough to do a research fellowship at Great Ormond Street Hospital in the late 1980s to look at a new chemotherapy drug called cisplatin. It was being combined with another drug called doxorubicin and surgery to treat paediatric liver cancer. The initial results of this combination were so encouraging that a small, international group of medics met and formed SIOPEL – a specialist liver tumour group – in 1987.
What we wanted to do
We wanted to foster international collaboration, and to design and run clinical trials specifically for children with liver cancer. It was exciting as this collaboration enabled more children to enter clinical trials, bringing answers to research questions in a reasonable timeframe.
The introduction of the MRI scanner also brought in clearer images of the liver. I remember being called down to the radiology department to look at the first MRI images of a child with liver cancer. Using these highly defined scan images, we established the pre-treatment extent of disease - PRETEXT system - which described the extent of the tumour across the four surgical sectors of the liver. Depending on how many sectors were involved, we grouped the tumours into PRETEXT I, II, III and IV permitting an image defined accurate analysis of the tumour at diagnosis.
Our impact
Before SIOPEL, liver cancer was staged and treated with surgery alone and only around 30% of children survived. The first SIOPEL trial, which introduced initial chemotherapy, followed by surgery and then more chemotherapy, increased the survival rate to approximately 70% for children with all types of liver cancer. Around 40 countries worldwide participated in this trial, with the study being run from CCLG in Leicester and funded by Cancer Research UK. The PRETEXT analysis from SIOPEL 1 validated the PRETEXT system as being prognostic, where the lower the PRETEXT at diagnosis the better the survival chances of the child.
Further SIOPEL studies mainly focused on the commoner form of liver cancer, hepatoblastoma (HB). Patients were grouped according to PRETEXT – those with standard-risk disease (SR PRETEXT I, II and III) and those with high-risk disease (HR PRETEXT IV) and/or with disease that had spread to the lungs (metastatic). Children with high-risk (HR) disease were treated with more intense treatment. The survival rate for children with metastatic disease increased from 0% to more than 50%. In children with standard-risk (SR) disease the treatment was made less toxic. SIOPEL 3 eliminated doxorubicin which is toxic for the heart.
By SIOPEL 6, over 90% of children with SR-HB were being cured with cisplatin and surgery. However, approximately 60% of children were being left with permanent hearing loss in both ears from the cisplatin. The trial centre had moved to Birmingham, I had been appointed principal investigator and like other SIOPEL trials we had funding from Cancer Research UK. SIOPEL 6 trialled sodium thiosulfate (STS), a drug pre-clinically tested in Portland, Oregon, and showed that STS could reduce cisplatin-induced hearing loss by 50%. STS was subsequently licensed, as Pedmark®, in the US for all children with localised cancer. It will soon be licensed in Europe. STS is currently available in the UK on compassionate grounds.
Today, SIOPEL is still a thriving, pioneering research group and new breakthroughs are continuously being sought to help all children diagnosed with liver cancer.
From Contact magazine issue 98 - Spring 2023
