Title: Systematic reviews of treatments for children’s cancer – central nervous system tumours.
Funder: Department of Health (England)

Abstract: Aim: To investigate the strength of evidence for the treatments of four key central nervous system (CNS) tumours affecting children and young people: High Grade Glioma (HGG); Low Grade Glioma (LGG) Ependymoma and Medulloblastoma (PNET). Background/rationale: Tumours of the brain and spinal cord - often known as central nervous system tumours - CNS tumours for short - are very rare in children and young people. On average 330 new cases per year, with an incidence rate of 3.56 per 100,000 in children aged 0 to 14 years. These are heterogeneous tumours, with the treatment and outcome often being tumour type (and sub-type) specific. No individual subtype has an age standardised incidence rate in children from 0 to 14 years higher than 1/100,000 and therefore each can be classed as a very rare disease. Unfortunantley they are difficult to treat, with patients more likely to die from these tumours than other tumours found elsewhere in the body. In addition patients who survive long term are often left with disease and/or treatment related chronic illness or disability. Methods: Six systematic reviews are planned on topics that have been prioritized by specialist clinicians and patient representatives. The reviews will be undertaken according to standard systematic review techniques, with each review following a priori protocol. Searches will be undertaken in electronic databases, namely Cochrane, Medline and Embase. Searches for ongoing studies will be undertaken in clinical trials.gov. and unpublished studies will be sought in relevant conference procedings. Two reviewers will select relevant papers according to specified inclusion cristeria and double data extract information onto data extraction sheets. This will be collated and analysed with appropriate statistical methodology. The reviews will be reported according to Preferred Reporting in Systematic Reviews and Meta-analysis (PRISMA) guidelines. Results: Reviews will be published in peer review journals and information will be dissemnated to relevant clinicians and patient groups. This is a vital initiative that will be of great benefit to children and young people with brain tumours not only with respect to gathering information with respect to trials that have already been undertaken but in directing future clinical research. Summary: These systematic reviews will lead to reduced variation in treatment and improved quality of care for children and young people treated according to guidelines based on systematic reviews which will map to domains 2, 4 and 5 of the NHS Outcomes framework: 'Enhancing quality of life for people with long-term conditions'; 'Ensuring that people have a positive experience of care'; and 'Treating and caring for people in a safe environment protecting them from avoidable harm'. In addition they will help to improve future research. Clinical trials into CNS tumours in children are resource intensive and have tended to develop based on national historical perspectives and sometimes by serendipity and circumstance rather than a strategic and systematic view a across the whole pathway from diagnosis through to long-term survivorship. The output from this research will result in a strategic overview of the current questions that need to be answered in the future regarding CNS tumours in children. Those questions can be prioritised by the number of patients they will affect and the likelihood of successfully answering the question. These outputs will particularly map to domains 1 and 3 of the NHS outcomes framework, 'Preventing people from dying prematurely' and 'Helping people to recover from episodes of ill health or following injury'. With the the majority of trials in paediatric oncology now run out of the Cancer Research UK Clinical Trials Unit (CRCTU) in Birmingham the authors are ideally placed to use the review outputs in designing future trials.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS