Medulloblastoma

Medulloblastoma - Definition, Prognosis and Treatment

Medulloblastoma is the most common malignant or high-grade paediatric brain tumour. At least 75% of medulloblastomas occur in the cerebellum at the back and base of the brain.

Medulloblastoma brain cancer is usually diagnosed as a grade 3 or grade 4 tumour. It is more common in boys than girls and is rarer in adults. It originates in embryonic (foetal) tissue hence is classified as an embryonal tumour, and is typically discovered during the first five years of life.

This type of tumour is rare in adults.

What is the survival rate for medulloblastoma?

Survival rates in children with medulloblastoma depend on the patient's age and if the tumour has spread.

If the disease has not spread, survival rates are above 60%, but if it has spread to the spinal cord, the survival rate is reduced.

Because medulloblastoma is such a rare disease in adults, prognosis is very much determined on a case by case basis. Like any high-grade brain tumour, the survival rate statistics will be lower than for patients with a low-grade brain tumour, for example.

The exact type of medulloblastoma makes a difference to the prognosis. For example, a WNT-activated medulloblastoma is considered relatively low-risk with a better prognosis than those classified as Sonic Hedgehog (SHH) activated, grade 3 or grade 4 (see below).

For children and adults with a recurrent medulloblastoma (where the tumour grows back quickly despite having treatment to remove it), the prognosis is shorter, with a five-year survival rate of less than 40%.

Advances in surgery, radiation, and chemotherapy are contributing to an increase in survival rates, but side effects of treatment can produce long-term challenges for patients, including cognitive difficulties along with psychological and social problems. Longer term support services may be required in order to maximise quality of life.

Research around the world is now focused on developing more personalised treatments that are more effective, with fewer side effects.

Are there different types of medulloblastoma?

Medulloblastomas are classified into four main groups using molecular and genetic analysis of biopsy tissue, and then into further subgroups using histology – variations identified on examination of tumour cells under a microscope. Tumours are thus given detailed, integrated classifications that are used to indicate a potential prognosis and guide treatment.

What do the different types of medulloblastoma mean?

The size, shape and physical characteristics of tumour cells when viewed through a microscope are reflected in names such as ‘large cell’ or ‘nodular’ medulloblastoma, but the four main groups of this tumour type are defined by how they act rather than how they look.

WNT-activated medulloblastoma

WNT-activated medulloblastoma is the most common form of medulloblastoma. It is named after the WNT pathway, a specific series of molecules which influence each other, and is a process that can in turn affect tumour growth.

Sonic Hedgehog (SHH) activated medulloblastoma

The SHH pathway also affects tumour growth (named after the video game character “Sonic the Hedgehog” by the scientists who discovered it). When messages are passed along molecules in the SHH pathway in a balanced way, it helps to control healthy embryonic development. Excessive SHH activity means that the body doesn’t stop producing this type of brain cell when it otherwise would do, so a tumour can then form from this build-up of cells.

Sonic Hedgehog pathway activation is a commonly associated with medulloblastoma in adults (patients aged 16 years or over), as well as those occurring in children under three years old.

Group 3 medulloblastoma

This is the most aggressive form of medulloblastoma and tends to spread through the ventricles of the brain and into the spinal cord. This type of tumour usually has extra copies of the MYC gene, referred to as MYC amplification.

Tumours will be tested for this as it is the most important indicator of a shortened prognosis in paediatric medulloblastoma. This is rare in adult medulloblastomas.

There is also a cell signalling pathway controlled by a protein called NOTCH1 that scientists believe is influencing the aggressive nature of these Group 3 tumours. Ongoing research projects and clinical trials are trying to identify effective drugs that could block the action of NOTCH1.

Group 4 medulloblastoma

The largest subtype, Group 4 medulloblastoma accounts for up to 30% of patients diagnosed with this tumour type. However, the molecular make-up of these tumours is the least well understood.

What are the symptoms of medulloblastoma?

Medulloblastoma often occurs in the cerebellum, the area governing motor functions such as movement, balance and co-ordination.

Symptoms resulting from medulloblastoma growth can include:

Problems with walking
Increased stumbling and falling
General co-ordination issues, with increasing clumsiness for example

When a tumour in the cerebellum grows, it can interfere with the circulation of fluid between the spinal column and the brain which can lead to a build-up of pressure inside the head.

This can give rise to additional symptoms such as:

Headaches that tend to be worse after lying down for a while (for example, on waking up in the morning)
Generally feeling tired or unwell
Failure to feed properly
Feeling sick or actually vomiting
Abnormal eye movements
Blurry vision caused by swelling at the back of the eye

If the tumour spreads down into the spinal cord, it can cause other symptoms such as:

Back pain that gets worse after resting or sleeping
Problems with walking
Trouble controlling bowel or bladder function.

What causes a medulloblastoma?

The causes of a medulloblastoma are not yet clear, although SHH-activated medulloblastomas can sometimes be associated with a pre-existing condition called Gorlin Syndrome, also known as nevoid basal cell carcinoma syndrome. Gorlin Syndrome can lead to various types of cancer, including basal cell carcinoma, the most common form of skin cancer.

Find out more about causes of brain tumours

What treatments are used for medulloblastoma?

Surgery to remove all or as much of the tumour as possible usually comes first. This may include the insertion of a shunt in order to divert or regulate the flow of cerebral spinal fluid and / or a biopsy to extract some brain tumour tissue for classification and prognosis.

Surgery is likely to be followed by radiotherapy and chemotherapy.

Find out more about brain tumour treatments

How can we find a cure for medulloblastoma?

Research we are funding across all of our Centres of Excellence will help lead towards finding a cure for a wide range of brain tumours.

Pioneering researchers at our Brain Tumour Research Centre of Excellence at Queen Mary University of London are learning more about the molecular and genetic make-up of these challenging tumours in order to identify new ways to treat them. The team are also focused on using glioblastoma stem cells to help develop unique, patient-specific treatments that could translate across more than one type of brain tumour.

Our team at the University of Plymouth Low-Grade Brain Tumour Centre of Excellence are researching a number of molecular pathways that influence immune system function, tumour metabolism and tumour growth in a range of low-grade brain tumours. It is hoped that their findings will translate into other tumour types in the future.

The team of research and clinical experts at our Centre of Excellence at Imperial College, London, are working collaboratively with other research institutions to investigate the effectiveness of arginine-depleting drugs in the treatment of high-grade glioma brain tumours. They are also studying the way in which the ketogenic diet works in brain cancer. It is hoped that their findings may translate into other tumour types in the future

Scientists at our Centre of Excellence in the University of Portsmouth are looking at mitochondria in glioblastomas, exploring ways to ‘shut down’ these ‘batteries’ that supply energy to the brain tumours. It is hoped that their findings will translate into other tumour types in the future.

We also fund BRAIN UK at Southampton University, the UK’s only national tissue bank registry providing crucial access to brain tumour samples for researchers from all clinical neuroscience centres in the UK, effectively covering about 90% of the UK population, and an essential component in the fight to find a cure for medulloblastoma brain tumours.

Medulloblastoma