Medulloblastoma is the most common embryonal tumour and accounts for 18% of all paediatric brain tumours. Peak incidence is at 5 years of age and approximately 70% of average-risk paediatric cases can be cured. Medulloblastoma patients are treated with surgery, chemotherapy and craniospinal irradiation. Because it targets the whole brain and spine, craniospinal irradiation results in severe long-term side effects such as hearing loss and dementia. These side effects take years to manifest and will be experienced by at least 60% of patients.
There are four defined molecular subgroups of medulloblastoma – WNT, SHH, Group 3 and Group 4. The 5-year survival rate for each subgroup varies from 30% for Group 3 tumours to 90% for WNT tumours. The reasons for these markedly different survival rates are unclear. One possibility is that treatment may be more or less effective in the different subgroups.
Proton therapy is expected to be introduced into standard UK practice within the next few years. Due to the tumour location and typical age of medulloblastoma patients, there is a lot of interest in using proton beam therapy to reduce radiation exposure in medullolastoma patients. Around 15% of paediatric medulloblastoma are already given proton therapy worldwide. However, there is limited experimental and clinical data available to support the use or disuse of proton therapy in medulloblastoma.
To take advantage of the definition of four molecular subgroups for medulloblastoma radiotherapy, the radiobiological sensitivities for each subgroup need to be determined. If these sensitivities differ between the subgroups, there is the potential to provide more personalised treatment regimens by changing treatment intensity. As an increasing number of paediatric patients are treated with proton beam therapy, investigating the relative radiosensitivity between protons and photons will also aid in treatment design.
The aim of this project is to examine the radiobiology of X-ray and proton therapy in medulloblastoma, to identify biomarkers of sensitive and resistant cell lines, and to examine the expression of these biomarkers in primary tumour samples. This research will provide data regarding the different medulloblastoma molecular phenotypes as well as potentially aiding clinical decision-making regarding treatment planning.