Research Training Fellowship: Dr Chris Howell

Published on 2 June 2010

Brain tumours in children under three – striving for better treatment

Each year, Action Medical Research awards these prestigious grants to help the brightest and best doctors and scientists develop their career in medical research. Dr Howell’s grant of £184,533 will fund his three-year study into life-threatening brain tumours in very young children, with the long-term aim of improving treatment.

Introduction

Dr Chris Howell has seen first hand the devastation that brain tumours can bring during childhood. To get the best chance of survival, many children undergo gruelling treatment with brain surgery, chemotherapy and sometimes radiotherapy.

Sadly, many children still die and survivors can be left with lifelong problems, meaning they have little chance of ever living independently.

Dr Howell is determined to change things for the better. He believes his research into what causes tumours in very young children, under three years of age, could ultimately help more children beat brain cancer.

He said: "This is a fantastic opportunity to carry out a substantial piece of work, answering important questions about how brain tumours develop in children. I will acquire research skills that will enable me to make a difference to the lives of children with brain tumours."

The problem

A devastating diagnosis

Around one in 10 of the children who die from cancer in the UK have a brain tumour called a medulloblastoma.^1,2 Young children, under three years of age, are particularly vulnerable.

“Diagnosis of cancer in any child is a devastating blow,” explains Dr Howell. “This is particularly true in cases of infant medulloblastoma, when the tumour occurs in children under three. Aggressive surgery, chemotherapy and sometimes radiotherapy are needed to give children the best chance of a cure. Treatment is extremely gruelling, causing unpleasant side effects and requiring long stays in a specialist hospital, often a long way from home.”

Despite undergoing this difficult treatment, 60 per cent of children under three years old still lose their lives to their brain tumour.³ And, sadly, most of the children who do survive are left with lifelong problems.^4,5

“The disease and its treatment have long-term effects on survivors, particularly on hormonal systems, such as growth, and on intellectual development,” says Dr Howell. “Ongoing problems with intellectual development mean that few survivors can expect to complete mainstream schooling, find employment or live independently as adults.”^4,5 Better treatments are urgently needed.

The research

What causes brain tumours?

Dr Howell is looking for genetic factors that cause medulloblastoma in children under three. He is also investigating whether a tumour’s genetic make-up influences the severity of the illness, and a child’s chances of survival.

Dr Howell is using DNA samples that have already been collected from around 80 infants with medulloblastoma, along with clinical information on how their illness progressed. Samples from around 200 older children with the condition are being used for comparison.

“This is a great project,” says Dr Howell. “I have everything I need to carry out a comprehensive study of the biology of infant medulloblastoma, including samples from large numbers of children, state-of-the-art equipment and the support of an established research group within a world-class institute. I am determined to ensure that this project is a success.”

Dr Howell’s focus on children under three is important:

• they do much worse than older children – only around 40 per cent survive compared with 70 per cent of older children³
• long-term effects on growth and learning are more severe in younger children
• research has already identified genetic changes that are linked to brain tumours in older children, but less is known about the under-threes.

Who benefits

Hopes of better treatments

Dr Howell hopes to improve the lives of young children, under three years of age, who have medulloblastoma, the most common malignant brain tumour in children.^1,2

“This research is essential if we are to achieve the dual goal of improving survival rates and reducing the disabling side effects of treatment,” explains Dr Howell. By boosting our understanding of disease biology, his work may lead to new ways predict how each child’s disease is likely to progress and, ultimately, to new treatments.

Children with the most life-threatening cancers could then be given the most aggressive treatment, in an attempt to save their lives. Children with less severe disease might be better off with less intensive treatment, because this might minimise side effects.

A committed researcher

As his career progresses, Dr Howell hopes to be at the forefront of efforts to find better treatments for children with brain tumours. “As a parent, you hope your child will grow up to be healthy and happy. Infant medulloblastoma is a big barrier to that. To be in the position to change this is a huge responsibility, but also very exciting, and why I wanted to be a doctor in the first place.”

This work is being supported by a generous donation from The Freemasons’ Grand Charity.

References

1. Pizer, B.L. and S.C. Clifford, The potential impact of tumour biology on improved clinical practice for medulloblastoma: progress towards biologically driven clinical trials. British Journal of Neurosurgery 2009; 23(4):364-75.
2. An Assessment of Need for Child and Adolescent Cancer Services in England and Wales. Final report, August 2004. Appendix 4: NRCT Mortality data for the 0-14 age group (Page 96) http://www.gserve.nice.org.uk/nicemedia/pdf/cacancer_2ndcons_assessment_...
3. Carlotti Jr C, Smith C, Rutka J. The molecular genetics of medulloblastoma: an assessment of new therapeutic targets. Neurosurgical Review 2008; 31(4):359-69.
4. Palmer SL, Reddick WE, Gajjar A. Understanding the Cognitive Impact on Children Who are Treated for Medulloblastoma. J Pediat Psychol 2007; 32(9):1040-9.
5. Kiltie A, Lashford L, Gattameni H. Survival and Late Effects in Medulloblastoma Patients Treated With Craniospinal Irradiation Under Three Years Old. Medical and Pediatric Oncology 1997; 28:348-54.