What is medulloblastoma?: A quick lesson on symptoms, diagnosis and treatment.

An overview by Stephen W. Gilheeney, MD, MMS
Clinical Instructor, Pediatric Neuro-Oncology
Department of Pediatrics
Memorial Sloan-Kettering Cancer Center

Medulloblastoma is the most common malignant brain tumor in children, affecting approximately 400 children per year in the United States, and comprising 20-25% of all brain tumors seen in pediatrics. Boys and girls are affected equally, usually within the first decade of life although teenagers and young adults have also been diagnosed with medulloblastoma. The disease arises in the cerebellum, the portion of the brain behind the brainstem that controls balance, coordination and fine motor movements. 

Different from cancers in adults, there is no known “cause” of medulloblastoma. Mutations in the genetic material of certain cells in the cerebellum give rise to medulloblastoma cells, but what exactly makes these mutations happen is not known. While there are some inherited syndromes that have a higher incidence of medulloblastoma, most cases arise in children where there is no history of medulloblastoma or other tumors in the family. 

Children with medulloblastoma most commonly present with headache. This is because the growing tumor begins to interfere with the flow of cerebrospinal fluid (CSF), the clear fluid that bathes the brain and spinal cord. This causes a process called hydrocephalus where the fluid filled spaces (ventricles) in the brain enlarge because of the poor flow of CSF. When this happens, children can develop severe nausea, vomiting, and lethargy. Families often notice this most in the morning though it can occur throughout the day. Other symptoms children can develop include:

• Unsteadiness while walking or running
Parents often say that their children are “tripping and falling more” or “walking like they’re drunk”

• Difficulty with fine motor movements
Some families will say that children begin to develop trouble tying their shoes or fastening buttons when they’ve already learned how to do so. Parents will also report that children’s hands seem “shaky” when they are reaching for things at a distance.

• Difficulty with rapid alternating movements
Parents may see children having trouble with games or actions that require moving the hands or feet back and forth quickly.

The first step in diagnosing medulloblastoma is a scan of the brain. A CAT scan (a computerized axial tomography scan) uses X-rays to take pictures of the body in slices. Medulloblastoma can usually be seen in the cerebellum, and enlargement of the ventricles in the brain are visible. Most doctors when they see this will also perform an MRI (magnetic resonance imaging) scan which uses a giant magnet to take pictures of the brain and tumor in different directions. MRI’s are also better at telling the difference between normal brain tissue and tumor.

The second step in diagnosing medulloblastoma involves removing the tumor and looking at thin, small slices of the tumor under a microscope. This is called “pathology” and is very important as different types of brain tumors are often treated in different ways. Figuring out exactly what type of tumor is present is, therefore, very important.

Once the diagnosis has been made, it is important to be certain that as much tumor as possible – if not all of it – has been removed. Doctors will perform an MRI scan of the brain after surgery to make sure. Doctors will also do an MRI of the spine because it is possible for tumor cells to spread to the spine through the CSF. Doctors will also do a lumbar puncture (also called a “spinal tap”) which involves putting a small needle in the back to obtain and look for tumor cells in the CSF, even if no tumor is seen on the spine MRI.

Once all of this testing has been done, doctors will determine if a patient’s medulloblastoma is “standard risk” or “high risk”. A patient has standard risk medulloblastoma if they are at least 36 months old, have a total or near total resection of the tumor, and have no evidence of tumor anywhere else in the brain or spine on MRI scan or lumbar puncture. A patient has high risk medulloblastoma if they are less than 36 months old, if only a subtotal resection could be performed, or if there is any evidence of tumor in the brain, spine, or CSF. 

Treatment for patients with medulloblastoma who are older than 36 months involves radiation therapy and chemotherapy. Radiation therapy is given to the entire brain and spine (craniospinal radiation) with a “boost” dose to the cerebellum. The dose of radiation to the brain and spine will vary depending on whether a patient is high risk or low risk. Chemotherapy is given weekly during radiation, and is then usually given in monthly cycles after radiation. Specific chemotherapy protocols can vary, so doctors will discuss the medicines they select and the reasons for choosing them with patients’ families. Young children (less than 36 months of age) often do not receive radiation, as doctors are worried about the potentially severe learning and developmental side effects that can arise from radiation treatment to a child’s brain this early in development. Treatment for children under the age of 36 months includes aggressive chemotherapy, with some doctors adding radiation at the end if the patient is greater than 36 months of age at that time.

With radiation and chemotherapy, current survival estimates for medulloblastoma are approximately 80-85% for children with standard risk medulloblastoma. Survival estimates for children under 36 months of age are lower, as are survival estimates for children whose medulloblastoma is considered high risk for other reasons. These numbers have increased to their present levels over the past 20 years due to research by large groups of pediatric oncologists throughout the country, as well as scientists working in laboratories – all with the goal of increasing survival, while decreasing long term side effects. Regardless, 15-20% of all patients with medulloblastoma will die of their disease, and those who survive can be faced with lifelong toxicities affecting growth as well as neurological and cognitive development. Further research to reduce toxicities and increase survival is ongoing.

When the monster reappears: Treatment for recurrent medulloblastoma.

After the initial treatment for medulloblastoma, most doctors will continue to follow their patients with frequent MRI scans. How frequently these scans are performed can vary from hospital to hospital, doctor to doctor, and treatment regimen to treatment regimen. MRI scans are more frequent at the beginning (usually three to four times per year) becoming less frequent (once or twice a year) as time goes by. Doctors are most worried about tumor recurrence.

Even with successful treatment advances over the past 25 years, current estimates are that approximately 20% of all patients diagnosed with medulloblastoma will develop a recurrence. Recurrence of medulloblastoma is more common at the primary site (where the tumor was originally), but can occur anywhere throughout the brain and spinal cord. Many of these recurrences are discovered only on an MRI, without the patient showing any symptoms. For patients who do show symptoms, location of the recurrence dictates what type of symptoms will occur. For that reason, patients’ families are advised to contact their child’s doctor if they notice any neurological changes.

Once a recurrence has been confirmed, doctors then have to decide how to treat it. They decide whether surgery, radiation, chemotherapy, or any combination of those are to be used.

Surgery – Doctors may try to remove the medulloblastoma if the recurrence is a single nodule or piece. However, doctors will sometimes weigh the benefits of taking out the tumor with side effects and risks of surgery and choose to shrink the tumor with chemotherapy or radiation instead. Medulloblastoma sometimes recurs as multiple nodules throughout the brain and spine (disseminated recurrence) or as a coating of tumor on the surface of the brain or spine (leptomeningeal recurrence). In those cases, surgery is not usually an option.

Radiation – Most children diagnosed with medulloblastoma have already had radiation to the entire brain and spine, with a boost to the cerebellum where the tumor originally was. In those cases, doctors will only give radiation areas of the tumor outside the cerebellum. Again, as with surgery, doctors will have to weigh the benefits of giving the radiation against the risks of radiation to normal tissues. Some children who develop recurrent medulloblastoma have never had radiation before – usually because they were less than 36 months of age when they were first diagnosed. In those cases, doctors may choose to have radiation in some portion of the treatment, but usually only once the patient has reached 36 months of age.

Chemotherapy – For most children with recurrent medulloblastoma, chemotherapy makes up the bulk of treatment. Doctors will use a number of different types of medicines to try and make all of the visible tumor disappear. Sometimes, doctors will also use something called high dose chemotherapy with autologous stem cell rescue. In this process, patients have their blood stem cells harvested with a special machine that stores them and then freezes them. Then, patients are given very high doses of chemotherapy. To help make sure that their blood counts return, doctors then transfuse the patient with their own stem cells – usually two or three days after chemotherapy is completed. This process lets doctors treat the tumor with very high doses of chemotherapy without having to worry about the bone marrow and blood cells being wiped out by chemotherapy.

Even with all of these treatment options, children with recurrent medulloblastoma have a very difficult road to travel. Doctors and scientists are still looking for different ways to treat recurrent medulloblastoma – including different chemotherapies, and different ways of giving radiation. Further research, however, is critical to curing these children.