Childhood Medulloblastoma
Dr.Ashis Kumar Ghosh
Assistant Professor
Assistant Professor
Paediatric Hematology and Oncology
Background
Twenty percent of all childhood cancers start in the central nervous system (CNS), which consists of the brain, the spinal cord,
and the surrounding fluid (cerebrospinal fluid, or CSF), lining tissues (meninges) and bone (cranium and vertebrae). Brain
tumors are the most common solid tumor of childhood with 24.5 cases per 1 million children, per year and about 20% of those
brain tumors found in children less than 3 years old. In the past several years, the incidence of pediatric CNS tumors has been
increasing. This increase is partially explained by medical advances, including improved imaging, which has led to earlier
detection and diagnosis of brain tumors.
There are many different types of pediatric CNS cancers. Two things determine the diagnosis, or type of tumor: 1) where in the
CNS the tumor starts, or thelocation,and 2) how the tumor looks under a microscope, also known as thehistology. Primary brain
tumors are tumors that arise in the brain, while primary spinal tumors grow in the spinal cord. However, some brain tumors can
spread to involve parts of the spine, and vice versa. On occasion, certain types of tumors can even spread to areas outside of
the CNS, such as distant bones or bone marrow, which is called metastasis.
This is where the concept of "staging" the tumor comes into play, and each tumor type has its own specific staging system. The
purpose of assigning a cancer stage is to help predict outcome as well as to guide treatment by appropriately applying what
has been learned in pediatric cancer clinical trials. Ultimately, every cancer treatment plan is individualized for every patient,
and takes into account not only the stage and clinical data, but also the goals and desires of the patient and his or her family.
What is medulloblastoma?
Medulloblastoma is a type of brain tumor that occurs in infants and young children. It represents about 20% of all pediatric CNS
cancers. By definition, medulloblastomas occur in the cerebellum, which is the back part of the brain that controls walking,
balance and fine motor coordination, among other things.
Who gets this tumor, and how?
Medulloblastoma almost always occurs in children less than 15 years old. About 20% of the cases occur in infants less than
two years old. There are approximately 400 cases diagnosed each year and the disease appears to be more common in boys
than girls.
The exact cause(s) of medulloblastoma are not known. It does not appear to "run in families" or to be directly inherited from the
parents. However, medulloblastoma is associated with certain chromosomal abnormalities that probably occur at some point
during a child's development.
What are the signs of medulloblastoma?
The most common symptom of this tumor is frequent, severe vomiting, that may especially occur in the morning. Less
commonly seen are morning headaches, nausea, confusion, and visual changes, such as double vision. Typically, children
with medulloblastoma come to the attention of parents and teachers because of unsteady walking and clumsiness with holding
things. All of these symptoms are consistent with a problem in the cerebellar region of the brain. For example, constant vomiting
results from excessive pressure in the brain due to tumor blockage of important pathways for cerebrospinal fluid flow.
Please note that the symptoms mentioned here do not necessarily or automatically mean a child has a brain tumor, but further
medical evaluation is required to rule out the possibility of a cerebellar tumor, such as medulloblastoma.
How is medulloblastoma diagnosed?
Anmagnetic resonance imaging(MRI) scan of the brain with gadolinium contrast-enhancement is the gold standard for detecting
medulloblastoma. It has a very characteristic appearance on MRI scan: a well-defined, solid-looking mass located in the
cerebellum, with fairly uniform contrast enhancement.
Medulloblastoma is a tumor type that can spread from the brain to the spine and/or CSF. Thus, part of the diagnostic workup
should also include a gadolinium-enhanced MRI of the spine. The search for disease spread to the spine can be supplemented
with a lumbar puncture. This is a procedure in which a thin needle is inserted into the lower back in order to obtain a sample of
the cerebrospinal fluid, looking for floating tumor cells (cytology). A definite diagnosis of medulloblastoma will generally be
made only after the tumor cells are examined under a microscope by a pathologist.
How is medulloblastoma staged?
Staging is a way of grouping cancer patients with similar diagnoses and similar extent of disease. Most CNS tumors remain
where they started, (ie: in the brain or in the spine), often referred to as "localized disease". However, medulloblastomas can
spread within the central nervous system in a process called "metastasizing". Approximately 30% of medulloblastomas have
spread (metastasized) to the cerebral spinal fluid (CSF) at diagnosis. Rarely, these tumor cells can gain access outside of the
CNS and metastasize to distant bone or bone marrow.
Generally,patients with medulloblastoma are staged as either “average risk” or “high risk” disease. This classification helps to
guide treatment planning. Average risk patients are those that are older than 3 years, have no metastatic disease, and have
less than 1.5 cc of residual tumor after surgery. If a child is under 3 years old, has metastatic disease, or has residual tumor left
in the brain after surgery, they will be considered as having "high-risk" disease.
How is medulloblastoma treated?
Surgery:
Surgery is typically the first component of therapy. It is very important to perform as complete a surgery as possible, with the
goal being removal of all visible tumor, while sparing as much surrounding brain tissue as possible. This is then confirmed with
a post-operative MRI scan of the brain to look for any leftover, or residual tumor. Based on what the MRI shows, the surgery is
classified as one of the following:
- Gross total resection = No evidence of any tumor left behind either at time of surgery or on post-surgery MRI
- Near-total resection = More than 90% of original tumor removed by surgery
- Subtotal resection = Anywhere from 51-90% of original tumor removed by surgery
- Partial resection = Anywhere from 10-50% of original tumor removed by surgery
- Any surgery that removed less than 10% of the original tumor is considered a biopsy, or sampling, of the tumor.
The ideal situation is a gross total resection, but this is not always possible. For example, sometimes the tumor is invading into
or adhered to other parts of the brain, making safe surgery very difficult. Nonetheless, the overall goal is to take as much of the
tumor out as possible without risking severe brain deficits, as the long-term survival of medulloblastoma patients is directly
influenced by the degree of surgery. In other words, the more complete the surgery, the better the long-term outcome. This is
also known as a maximal safe resection.
The surgeon attempts to balance the need to remove as much tumor as possible without damaging healthy brain tissue. Some
children will develop a syndrome called posterior fossa syndrome after brain surgery in the area of the cerebellum. This is
associated with difficulty swallowing, balance deficits, mutism (a speech disorder that leaves the child unable to speak), poor
muscle tone and emotional lability (changes in emotions). These neurologic deficits may remain for months, but usually
improve slowly. Although historically this was seen in up to 15% of children, the rate of this has been noted to occur less
commonly at pediatric neurosurgical centers.
Radiation Therapy
After surgery, external radiation to the entire CNS (craniospinal irradiation, or CSI) is recommended to prevent the tumor from coming back in this area (recurrence, or relapse). This is the region that is most at-risk for the tumor returning. The radiation
dose to the entire brain and spine is dictated by several factors, including whether the tumor has spread into the spine or into
different regions of the brain.Even after a complete resection with no evidence of spread, low dose radiation to the brain and
spine is very important for overall cure of the disease.
After radiation of the whole brain and spine with a lower dose of radiation, the area of the original tumor, including where the
surgeon operated, continues to receive radiation to a higher final dose (so-called radiation "tumor bed boost"). This is because
the region in the brain where the tumor first started is the most likely place to still have some lingering, unseen, microscopic
tumor cells. Historically, the entire cerebellum has been boosted to this higher radiation dose, putting normal structures
including the inner ear and memory structures at risk for radiation damage. In recent studies, only the tumor bed has been
boosted with similar success, which allows for protection of normal tissues. The development of intensity modulated radiation
therapy (IMRT), a more precise form of radiation, also allows a decreased radiation dose to important structures near the
posterior fossa.
Much attention has understandably been paid to the possible long-term complications of radiation therapy to the brain and
spine of a growing child. These can include deficits in memory, learning, social/emotional adjustment, hormone levels, hearing,
and growth problems. The development of such side effects depends on many factors, including extent of pre-radiation surgery,
amount and location of brain that is treated with radiation, age of the child at diagnosis, and how much radiation dose is given,
among others. Because the side effects are very dependent on age (which is reflective of their stage of development), CSI is
often deferred, or delayed by the use of chemotherapy, for children under the age of 3 years old.
However, modern radiotherapy techniques and proper attention to minimizing the radiation dose to important brain structures,
whenever feasible, can allow for safe and effective treatment, even in younger children. While no therapy is without side effects,
radiation therapy can be planned and delivered in such a way as to minimize potential long-term side-effects. This is best
accomplished at a major radiation oncology center where physicians and staff are familiar with pediatric patients and
technologically capable of treating childhood cancers.
Proton Radiotherapy
Even though the actual craniospinal volume that is irradiated is small, a large volume of normal tissue is exposed to radiation
with photon radiotherapy (traditional radiation therapy), including the heart, lung, bowel, gonads, and vertebral bodies.Proton
radiotherapyoffers a major potential advantage over photons for the radiation of the spinal canal given its biologic properties.
Photons (which are used in traditional radiation) enter the body, reach the tumor and continue through the body, exiting on the
opposite side. This exposes the tissues in front and behind the tumor to radiation and, in turn, the risk for damage. Proton
therapy works differently; entering the body and reaching it's peak dose at the tumor and stopping, exposing tissues in front of
the tumor to lower doses of radiation and tissues behind the tumor to virtually no radiation. This translates into improved dose to
the target volume while sparing normal tissues and reducing side effects and toxicity. Proton therapy can also prevent radiation
dose to normal tissues for the cranial boost, especially for sensitive structures, such as the middle ear. Proton therapy is
available at select centers worldwide and is used for many children who require radiotherapy for medulloblastoma.
Follow-up Care and Survivorship
After treatment for childhood cancer, the patient will be followed closely to monitor for the cancer coming back, to help them heal from ongoing side effects, and to help them to transition to survivorship. Initially they will be seen often and have ongoing
tests to monitor their health. As time goes on, these visits and testing will become less frequent. The oncology team will discuss
each patient’s individual follow up plan with them. Patients who have had craniospinal radiation should discuss need for
hearing tests, visual tests, hormonal screening, cardiac and lung function tests, and early breast cancer screening with their
healthcare providers.
Survivors often wonder what steps they can take to live healthier after cancer. There is no supplement or specific food you can
eat to assure good health, but there are things you can do to live healthier, prevent other diseases, detect any subsequent
cancers early and work with the social and emotional issues, including insurance, employment, relationships, sexual
functioning, and fertility, that a prior cancer diagnosis sometimes brings with it. Your oncology team is there to support you and
can help you find support resources.
It is important to have a plan for who will provide your cancer-focused follow up care (an oncologist, survivorship doctor or
primary care doctor). Talk with your oncology team about developing a survivorship care plan. If you would like to find a
survivorship doctor to review your history and provide recommendations, you can contact cancer centers in your area to see if
they have a survivor's clinic or search for a clinic ( Cont.)
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