Professor Chris Clark, UCL Institute of Child Health
Wilms’ tumour is a childhood kidney cancer, mainly affecting the under fives. There are a number of subtypes of Wilms’, some of which carry a poor prognosis, but currently diagnosis can only be made following surgery, which follows four to six weeks of pre-operative chemotherapy. This project will pioneer the use of advanced MRI techniques to determine tumour subtype, enabling a more personalised approach to the management of each child’s disease.
Amount of grant: £88,559 | Date of award: May 2015
Around 80 children are diagnosed with Wilms’ tumour, a cancer of the kidney, every year in the UK. Most of these young patients are under the age of five years.
The overall survival rate is around 90%, but there are different subtypes of Wilms’ and some of these have a worse outlook.
In the UK, Wilms’ tumour patients are treated with pre-operative chemotherapy for four to six weeks to shrink the tumour prior to surgery. Further chemotherapy is usually given after surgery to reduce the risk of the tumour returning (relapse).
Certain types of Wilms’ tumour respond well to chemotherapy but others are more resistant.
Currently the tumour subtype can only be determined by microscopic examination of the tumour removed at surgery. This is used to select high-risk patients for more intensive post-operative treatment.
If the tumour subtype could be determined earlier, at diagnosis, this would allow earlier tailoring of treatment to optimise the outcome for each patient. Also, high-risk components of the tumour could be identified prior to initial biopsy and subsequent surgery, to aid diagnosis and reduce the risk of relapse.
Building on the results of a successful pilot study, Professor Clark and colleagues will explore use of an advanced MRI technique known as diffusion-weighted imaging (DWI) to determine a patient’s tumour subtype non-invasively and predict the response to chemotherapy.
The team will carry out a DWI scan in each patient both before and after their pre-operative chemotherapy. The tumour will then be removed surgically and subjected to microscopic examination to confirm the tumour subtype. Tissue will also be sent for molecular analysis to determine the presence of any genetic alterations.
The information from the before- and after- DWI scans will show how the cellular structure of the tumour has changed as a result of chemotherapy. This will help us to understand the differences in how the subtypes of Wilms’ respond to chemotherapy.
The DWI data will be combined with the data from the microscopic examinations and the molecular analyses to see if, in future, the imaging data alone could be used to determine which patients have a high-risk tumour.
About the research team
..the pilot investigation by this group has already gained attention in the international community.
External reviewerThis research is based at the UCL Institute for Child Health (ICH) and Great Ormond Street Hospital (GOSH). GOSH is one of the UK’s major referral centres for children with Wilms’ tumour; the team there sees around a quarter of all Wilms’ patients for surgery. GOSH also receives tissue and imaging scans on all cases registered in the national ‘IMPORT’ study of kidney tumours.
Professor Chris Clark is Head of Developmental Imaging and Biophysics Section at ICH. He is a recognised expert in the application of this type of MRI technology to children; cancer imaging is one of the main themes of his research.
He brings together a number of internationally leading research groups in the fields of paediatric cancer imaging, molecular biology and histopathology to deliver this project, including Professor Kathy Pritchard-Jones and Professor Neil Sebire.
Kathy Pritchard-Jones is one of the UK’s leading experts in childhood cancer. She is an Honorary Consultant Oncologist at GOSH and Professor of Paediatric Oncology at ICH, where she heads a laboratory for research into the molecular biology of Wilms’ tumour.
Neil Sebire, Professor of Paediatric Pathology at GOSH/ICH, is an internationally established expert in paediatric tumour pathology and is involved in a number of research projects relating to Wilms’ tumours.
What difference will this project make?
The early identification of Wilms’ tumour subtype and subsequent improved patient stratification meets an unmet clinical need in the management of patients with Wilms’ tumour.
The expectation is that the techniques being pioneered under this project would be used to help assess the risk/benefit ratio of changing pre-operative chemotherapy and/or timing of surgery on a patient-by-patient basis. It will also improve planning of kidney-sparing surgery, particularly where both kidneys are affected by cancer.
This will allow doctors to implement a more personalised approach to the management of this disease, helping to improve survival in children with high-risk disease and reducing the overall burden of treatment and potential for late-effects in children with standard- and low-risk disease.
Read more: About Wilms’ tumour | Patient story: Kodie