Medulloblastoma

Medulloblastoma belongs to a category of childhood cancers know as CNS (Central Nervous System) cancers which include tumours of the brain and the spine. Each year over 400 children are diagnosed with CNS, of which 15-20% are Medulloblastoma.

Until recently Medulloblastoma was classed as a primitive neuro ectodermal tumour (PNET) however recent research has shown that Medulloblastoma tumours have different characteristic to PNET tumours, and are now referred to as embryonal.

The cause of Medulloblastoma is mostly unknown however, there is an increased risk with some cancer syndromes that are family inherited. Around 5% of cases of medulloblastoma are linked with either:

• familial adenomatous polyposis (FAP) – sometimes known as Turcot syndrome
• nevoid basal cell carcinoma syndrome (NBCCS) – also known as Gorlin syndrome

Medulloblastoma is known as an embryonal tumour because it develops from cells that are left from the early stages of our development. Thanks to research, genetic tests are now possible to identify the genes, proteins and makeup of the tumour. Along with the location of the tumour, this information can be used to class Medulloblastoma into four sub categories:

WNT
WNT Medulloblastoma is located in the fourth ventricle, one of four cavities of space in the brain filled with fluid.

WNT accounts for around 10% of Medulloblastoma cases and are most common in females and older children with 10 year olds being the most diagnosed. 5-10% of WNT Medulloblastomas have spread at diagnosis. Outlook is very good and WNT Medulloblastoma rarely recurs.

SHH
SHH Medulloblastoma is associated with a condition known as Gorlin Syndrome which causes an over-activation of cells leading to a tumour.

SHH accounts for around 30% of Medulloblastoma cases and is most common in infants under three. 15-20% of SHH Medulloblastomas have spread at diagnosis. If SHH Medulloblastoma recurs it is usually local (in one area)

Group 3
Group 3 Meduloblastoma accounts for around 25% of Medulloblastomas and is more common in males and children up to the age of 10.  The tumour is usually located in the fourth ventricle and 30-25% of cases have usually spread at the point of diagnosis.

Group 4
Group 4 Medulloblastoma is the most common type of Medulloblastoma accounting for around 35% of all cases. It can be found in all groups, but is more common in males. 35-40% of Group 4 Medulloblastomas have spread at diagnosis and if Group 4 Medulloblastoma recurs, it is usually metastatic.

Doctors will use a range of methods to diagnose Medulloblastoma including a physical exam, blood tests and neurological exams to assess the function of the brain. These can include reflexes, memory, co-ordination, vision and hearing. Typically a child will also have a CT scan and an MRI scan to evaluate the tumour.

A lumbar puncture may also be done to assess the CNF Fluid – the fluid that surrounds your brain and spine.

Doctors will typically need to do a biopsy to assess the tumour which means they may not be able to tell you what type of Medulloblastoma your child has until a biopsy has been taken. Once doctors are able to assess the the biopsy under the microscrope, the shape and size will be used to classify the Medulloblastoma:

Classic medulloblastoma is made up of small, round cells. The cells are close together and have dark nuclei.

Desmoplastic/nodular medulloblastoma appears as circular nodules ringed by connective tissue with cells closely packed together.

Medulloblastoma with extensive nodularity (MBEN) shows more nodular regions within the tissue.

Anaplastic medulloblastoma is made up of cells that are irregularly shaped.

Large cell medulloblastoma has tumor cells with large nuclei. Anaplastic and large cells often occur together and are grouped as large cell anaplastic (LCA) tumors which is why some people refer to there being 4 types of Medulloblastoma.

Medulloblastoma will also be given a stage which signifies the spread of the disease;

• M0: The tumor is localized with no spread of disease.
• M1: Tumor cells are found in the cerebrospinal fluid (CSF).
• M2: There is evidence of spread of disease within the brain (intracranial).
• M3: The tumor has spread to the spine.
• M4: The tumor has spread outside the central nervous system (CNS). Common sites for metastases include the bones, lungs, and liver.

Treatment for Medulloblastoma will depend on the type, grade and progression of the tumour as well as the age and general health of the child who has been diagnosed. Each child will have a specialist team who decide the best course of treatment for the child. Parents are always heavily involved in decisions made about the child’s treatment and care.

Surgery
Most treatment regimes will start with surgery to remove as much as the tumour as possible. Depending on the size of the tumour, some children may need chemotherapy before surgery in order to shrink the tumour.

During surgery a shunt may be fitted to drain any CNF fluid causing pressure in the head and a biopsy will likely be taken to allow scientists to find out what type of Medulloblastoma it is. This will then help to form further treatment decisions.

Once doctors are able to assess the Medulloblastoma your child has, they will be placed into a high risk or standard risk group which help to guide the course of treatment that is needed. All children under 3 are placed into the high risk group along with children whose Medulloblastoma has spread. There are other factors that may place a child into the high risk group.

Chemotherapy
Chemotherapy is commonly used after surgery alongside radiotherapy. Doctors will avoid radiotherapy for children under 3 years old because the chance of developing long term side effects is increased. In these cases, chemotherapy may be used to delay the Medulloblastoma until the child is old enough for radiotherapy. There are many types of chemotherapies that doctors may use including: carboplatin, vincristine, cyclophosphamide, cisplatin, lomustine, and methotrexate.

Radiotherapy
Unless the child is under 3 years old radiotherapy is typically used to treatment Medulloblastoma. Children need to stay still for radiotherapy and so a general anaesthetic may be used in younger children. The dose of radiotherapy needed will depend on the tumour itself and the type of radiotherapy used will also depend on the type of Medulloblastoma. A child could have x-ray radiotherapy or proton beam radiotherapy.

Posterior Fossa Syndrome
Around 25 – 30% of children who have surgery at the back of the brain can develop Posterior Fossa Syndrome which causes a range of side effects that can include difficulty swallowing, talking, or walking. These effects can be mild and can appear up to a week after surgery. These effects may improve over weeks and months, however they may not go away at all. Treatment for Posterior Fossa Syndrome may include physiotherapy, speech therapy and occupational therapy.

The overall five-year survival rate for Medulloblastoma is approximately 70% in cases where the tumour has not spread. If the disease has spread to other parts of the body survival rates are close to 60%. Sadly 33- 35% of children have medulloblastoma that has spread when they are first diagnosed, this can be down to a delay in diagnosis due to symptoms being mistaken for other illness, until they progress and become more severe.

The survival rate for Medulloblastoma can also depend on other factors including the type, subtype and grade of Medulloblastoma. For example Group 3 Medulloblastoma has a survival rate of just 50%. Age and if the cancer is new or recurring can also affect survival rates, alongside the location of the tumour.

It is important to remember that no two children are the same, so it is always best to discuss your child’s outlook with your care team and follow their advice.

Relapse
Sadly, relapse occurs in around 30% of children with Medulloblastoma. In recent study, 86% of children with relapse, their Medulloblastoma had spread at time of the relapse being diagnosed. Their survival rates were as low as 18%.

Late-Effects
Many children who survive Medulloblastoma will develop long term disabilities known as late effects. These late effects can be down to the side effects of surgery, chemotherapy and radiotherapy and can vary in severity. Children may go on to struggle in their daily lives, in education and then employment when they are older.