Medulloblastoma

What is Medulloblastoma?

Leukemia is the most common type of cancer affecting children, but when we look at solid tumors, brain tumors top the list, particularly in children. Among these, medulloblastoma is the most common malignant brain tumor, making up about 20% of all child brain tumors. This type of cancer originates from a specific region in the brain called the cerebellum.

Medulloblastoma is a high-grade, aggressive tumor that can spread through the liquid surrounding the brain and spinal cord, known as cerebrospinal fluid.

In the early stages, medulloblastoma can sadly cause death in about 15% of cases. However, positive news is that cure rates can be as high as 60% using current treatments. The key treatment approach involves surgical removal of the tumor, with radiation and chemotherapy used either before or after surgery to kill remaining cancer cells. Five-year survival rates can vary between 50% to 90%. This variability is influenced by factors such as the child’s age at the time of diagnosis, whether the cancer has spread at the time of diagnosis, and the specific type of medulloblastoma.

Even after successful treatment, there are potential long-term effects like cognitive issues, neurological problems, and hormonal imbalances. These side effects highlight the need for ongoing research to find more effective treatment methods that cause fewer side effects.

What Causes Medulloblastoma?

The exact cause of medulloblastoma, a type of brain tumor, is not quite clear. Some research has suggested that what a mother eats or any blood or immune disorders she might experience during pregnancy could be linked to it. Other studies have mentioned a possible connection with certain viral infections during early childhood, such as John Cunningham (JC) virus or human cytomegalovirus (CMV), which are both types of common viruses.

There also seems to be a familial link to medulloblastoma, as it is sometimes seen more commonly in certain families, suggesting a genetic connection. Additionally, medulloblastoma is known to be associated with several syndromes. These include Gorlin syndrome, a genetic condition that affects many parts of the body and increases the risk of developing various cancerous and noncancerous tumors; Fanconi anemia, a blood disorder that stops your body from repairing damaged DNA; Turcot syndrome, a condition that increases the risk of developing certain types of brain tumours; and Li-Fraumeni syndrome, a rare inherited genetic disorder that greatly increases the risk of developing several types of cancer, particularly in young people.

Risk Factors and Frequency for Medulloblastoma

According to data from the Surveillance, Epidemiology, and End-Results (SEER) database spanning from 1973 to 2007, it was found that medulloblastoma affects around six out of every million children every year. This translates to roughly 450 new cases among children yearly. The disease is most common in children aged 4 to 9, who account for 44% of cases. Adolescents from 10 to 16 years old make up 23% of cases, while infants and toddlers from 0 to 3 years old only account for 12% of cases. Interestingly, children are ten times more likely to get medulloblastoma than adults, and boys are 1.5 times more likely to have it than girls.

• Each year, around six out of every million children get medulloblastoma, amounting to about 450 new cases.
• The age group most affected by this disease are children aged 4 to 9, accounting for 44% of all cases.
• Adolescents aged 10 to 16 contribute to 23% of the cases.
• Infants and toddlers aged between 0 to 3 years only make up 12% of the cases.
• The occurrence rate in children is ten times higher than in adults.
• Boys are 1.5 times more likely to have medulloblastoma than girls.

Signs and Symptoms of Medulloblastoma

Medulloblastomas are tumors that often start in the cerebellum. Their growth can disrupt the normal function of the brain, leading to a variety of physical symptoms. Most common include clumsiness, problems with walking, and hydrocephalus. Hydrocephalus is a condition where fluid builds up in the brain and can lead to headaches, particularly in the early morning, feeling sick, vomiting, double vision and blurry vision.

This type of tumor often grows into the fourth ventricle of the brain. Thus, it’s common to see symptoms of obstructive hydrocephalus in these patients, such as vomiting, headaches, and lethargy. The time duration from when symptoms first appear to when this tumor is diagnosed is usually short – about two to three months.

Almost everyone with medulloblastomas show early signs of increased pressure in the skull. This pressure is typically tied to headaches that get worse in the morning and ease up as the day goes on. When Cushing’s triad symptoms – high blood pressure, abnormal breathing, and a reduced heart rate – appear, immediate treatment is needed because this indicates a herniation, or shifting, of brain tissues.

In addition to these symptoms, the tumor can cause ataxia, a lack of muscle control during voluntary movements, and unsteadiness of the trunk of the body. If the tumor extends to the brain stem, it could result in cranial nerve problems. Symptoms could include double vision, hearing loss, weakness in the facial muscles, and a tilt of the head.

During physical examination of the patient, checking the back part of the inner eye, an optic pallor or papilledema may be seen. Paralysis of the abducens nerve, that is responsible for allowing the eye to look sideways, may also occur. The “sun setting” sign, where a part of the iris remains covered by the lower eyelid, may be seen in some infants. Also, measuring the size of the infant’s head might show an increase in its size.

Testing for Medulloblastoma

As part of the diagnosis process for potential brain tumors, different types of tests and investigations may be completed.

These often include routine lab tests, which can involve checking the health of your thyroid by measuring its hormone levels in your blood.

A Computed Tomography (CT) scan of your brain can also be done, which gives doctors clear and detailed images of your brain. In some cases, the CT scan may reveal a mass in the 4th ventricle, a part of the brain located at the base of the skull. If there, the mass would usually become more visible after injecting a contrast dye, a substance that enhances visibility in medical imaging. In addition, Hydrocephalus, a condition where there’s an accumulation of cerebrospinal fluid (CSF) within the brain, is often seen in brain tumor patients.

While CT scans provide quality images, Magnetic Resonance Imaging (MRI) typically paints a much clearer picture. MRI might be performed on all the patients because this method can reveal more detailed images of the brain and can also be used to check if there is any disease left after the surgery. A spinal MRI can also be performed to potentially catch tumour spread into the spine.

There are also additional tests that might be done in preparation for treatment. An audiometry test, a hearing test, is usually done prior to starting a kind of chemotherapy drug called cisplatin. An echocardiogram, which captures the images of your heart, and pulmonary function tests that measures how well your lungs function, are usually done to establish baseline health parameters before starting chemotherapy.

In some cases, a lumbar puncture, a procedure where a small amount of CSF is drawn from your spine for testing, may be done to check for the spread of the tumor. It’s important to note that even if an MRI test is positive for a tumor, the CSF may still appear to be normal. A fundoscopy, an eye examination to check the health of your retina and optic nerve, is typically done before a lumbar puncture is performed. Furthermore, after surgery, it’s necessary to wait at least 2 weeks before conducting a lumbar puncture because post-surgery changes in the brain might lead to false-positive results.

Treatment Options for Medulloblastoma

Current treatments for medulloblastoma, a type of brain cancer, include a combination of surgery, chemotherapy, and radiation therapy. These methods have successfully led to a cure in about three-quarters of patients with a medium-risk type of this disease. However, up to 80% of survivors end up with serious side effects including intellectual challenges and a deficiency in growth hormone. For high-risk patients, the survival rate is up to 50%. This is often due to the cancer spreading beyond the brain and the younger age of patients upon diagnosis, which limits the treatment options available.

Thanks to new ways of classifying the disease, scientists have been able to develop more targeted treatments aimed at disrupting specific pathways that play a key role in the development of the cancer. Let’s look at a few of these:

The SHH pathway: This pathway is marked by a process that involves a compound called Sonic Hedgehog. New drugs such as SMO inhibitors, specifically cyclopamine, HhAntag, vismodegib, saridegib, and sonidegib, are currently being studied to target this pathway. Vismodegib and sonidegib, in particular, are currently in phase 2 of clinical trials in patients with the SHH subgroup of medulloblastoma.

The WNT pathway: This pathway is deemed active when beta-catenin, a protein involved in various cellular processes, is not properly broken down due to mutations. New drugs have thus been developed to target steps in beta-catenin’s activities. These include naturally-occurring substances that can inhibit certain protein transformations, cantharidin, norcantharidin, and ginkgetin. However, given that patients in this subgroup have a good prognosis (with a survival rate greater than 90% over 5 years), efforts are currently focused on limiting the side effects of radiation therapy.

Non-SHH/WNT medulloblastoma: Not much is currently known about the specific pathways involved in this type of medulloblastoma. As a result, developing targeted therapies for it has been challenging. However, potential strategies, including inhibiting the cell division process and regulating certain proteins, are currently under investigation.

What else can Medulloblastoma be?

• Choroid plexus carcinoma
• Ependymoma
• Teratoma

Surgical Treatment of Medulloblastoma

The main goal of surgery is to remove as much of the tumor as possible and to ease the blockages in the flow of CSF, which stands for cerebrospinal fluid – a fluid present in the brain and spine. However, surgeons need to be cautious during the procedure because the tumor can be crumbly and can spread very quickly. After undergoing surgery, more than 40% of patients may still have some neurological problems remaining. These issues could include difficulties with cerebellar functions, which are those related to the cerebellum in the brain such as balance and coordination, as well as possible speechlessness, problems with cranial nerves that may affect senses and motor abilities, and muscle weakness on one side of the body.

It’s important to note that some of these symptoms might get better over time, but comprehensive rehabilitation will be necessary. Sadly, at least 50% of patients may end up with lasting disabilities.

In most patients, a procedure referred to as a ventriculoperitoneal shunt is necessary to alleviate the condition of hydrocephalus, which is a buildup of fluid in the brain. This procedure involves inserting a tube to drain excess fluid. Additionally, some patients might find relief from a procedure called an endoscopic third ventriculostomy, which is a surgery that allows fluid to bypass a blockage in the brain. In addition to the need for a central venous access, which is a catheter inserted into a large vein for delivering medications, an Ommaya reservoir is often implemented for administering chemotherapy directly into the fluid around the brain and spinal cord. But keep in mind, there are risks associated with these procedures and technical complications are common.

What to expect with Medulloblastoma

The chances of recovering from medulloblastoma, a type of brain tumor common in children, largely depends upon a variety of factors. These include the patient’s age, the stage of the tumor, how much of the tumor remains after surgery, and how well the patient responds to treatment.

For instance, children with the WNT subtype of medulloblastoma typically have a better chance of recovery. However, children with MYCN or MYC types tend not to fare as well. Unfortunately, even after successful treatment, many patients may experience long-term neurological and cognitive issues. These can involve learning difficulties, problems with growth, and hormonal imbalances. The primary cause of these complications is the craniospinal radiation used in treatment.

Looking at survival rates, when it comes to average risk patients — those with no significant remaining tumor and no evidence of spreading — the five-year survival rate is 85%.

For those in the high-risk group, the five-year survival rate drops to less than 40%.

Survival rates can vary even more for children less than three years old, ranging from 30-70%. Where metastatic disease (cancer that has spread to other parts of the body) is present, the prognosis is worse. However, children with SHH or WNT activated lesions generally have better survival rates.

Furthermore, medulloblastoma can be divided into as many as 12 different subtypes thanks to advances in understanding gene behavior and patient outcomes. This allows doctors to identify which types may have better or worse survival rates. For example, the WNT subtype has a five-year survival rate of 97-100%. This is the highest among all subtypes. The SHH subtype’s rate is between 70%-88%. Meanwhile, other subtypes are believed to have the worst outcomes, though group 4 patients tend to have a better survival rate (65%-85%) than group 3 (40%-65%). Particularly, myc amplification cases seem to have the poorest outcomes within group 3 patients.

Possible Complications When Diagnosed with Medulloblastoma

After brain tumor treatment, people often experience side effects. These can include:

• Headaches
• Vomiting
• Problems with coordination and balance
• Posterior fossa syndrome, a group of symptoms like changes in behavior, trouble talking, and movement issues, typically seen after a surgery in the lower back part of the brain
• Infection or malfunction of a shunt, a device to drain excessive fluid from the brain
• Bleeding in the brain
• Weakening or paralyzing in one side of the body
• Problems with thinking, focusing or remembering
• Sleeping excessively, a condition called somnolence syndrome
• Damage to brain tissue due to radiation therapy
• Hearing damage as a result of chemotherapy drugs
• Development of new cancers
• Complications due to chemotherapy, which may vary widely

Preventing Medulloblastoma

It’s essential for the patients, or more often the parents if the patient is a child, to fully understand the expected outcome of the illness. They also need to be properly informed about all the risks associated with the treatment due to the critical location of the tumor. Only after being supplied with all this information and giving their consent, can the doctors proceed with any kind of surgical procedure.