What is a high-grade glioma?
High-grade gliomas are a type of cancer that can develop in any part of the central nervous system, which includes the brain and the spinal cord. A glioma is a name for a tumour of glial cells. These are the supporting cells of the nervous system. High grade means that the glioma is more aggressive and can grow quickly.
High-grade gliomas can affect children of any age. The tumours most often originate in the different hemispheres of the brain (the upper part of the brain) or the brain stem. High-grade gliomas coming from the brain hemispheres are often called supratentorial high-grade gliomas. When coming from the brainstem, high-grade gliomas are called diffuse brainstem gliomas or diffuse pontine gliomas.
High-grade gliomas are either World Health Organization (WHO) grade 3 or grade 4 tumours. This classification is done after examination of a biopsy specimen under the microscope by a pathologist. Grade 3 and 4 tumours tend to grow quickly and spread faster than tumours of a lower grade. Grade 3 tumors are also called anaplastic astrocytoma and grade 4 tumors are also called glioblastoma. Other more complex high-grade gliomas include:
- oligoastrocytoma
- pleiomorphic xanthoastrocytoma
- gliosarcoma
What are the symptoms of a high-grade glioma?
Symptoms of a high-grade glioma will be different depending on where the tumour is located in the brain or central nervous system.
The most common sign of a high-grade glioma is a headache, or a headache that causes vomiting. Other symptoms include:
- Seizures
- Vision problems
- Hearing problems
- Speech problems
- Balance problems (ataxia)
- Changes in behavior
- Sluggishness and/or sleepiness
- In infants: a bulging fontanelle (soft spot) or increased head size
What causes a high-grade glioma?
The exact cause of high-grade gliomas is unknown. Currently, there is no definite proof that environmental factors such as food or chemicals can cause brain cancer in children. Development of such cancers are usually random and cannot be prevented.
In rare cases there may be a genetic cause. Your child’s doctor may request molecular testing from the tumor and a blood sample to identify if this is the case. Please let your child’s doctor know if anyone in the family has previously developed cancers of the blood, brain or the digestive system, or if your child has had other medical problems.
How many children have high-grade gliomas?
Each year, 150 to 180 children in North America are diagnosed with a high-grade glioma.
How are high-grade gliomas diagnosed?
Typical imaging techniques such as magnetic resonance imaging (MRI) or computerized tomography (CT) scans may be used to determine if a tumour is present, but the actual diagnosis of a supratentorial high-grade glioma depends on histo-pathological testing.
Histo-pathological testing is when a biopsy is done to remove a small sample of the tumour from the brain. The sample is then studied under a microscope for the presence or absence of certain characteristics. This helps determine the specific type of high-grade glioma.
Molecular tests may be required to:
- accurately classify the tumor sub-type to understand how aggressively it will behave
- understand whether the tumor could be treated with newer modalities like targeted or immunotherapy, or whether your child could participate in a clinical trial
- find whether the tumor is arising from any genetic defect that could put other family members at risk and if so, monitor them early before they develop a tumor
What is staging?
Staging determines the type of treatment that is most effective for a type of cancer. This depends on several factors, including:
- the child’s age
- the type and size of tumour
- whether the cancer has spread to other parts of the body
Complete staging, using an MRI of the spine and examination of the cerebrospinal fluid (CSF), is not usually a part of the initial diagnostic testing. However, high-grade gliomas can spread, and if there are any concerns, complete staging will be considered by your child’s doctor.
How are high-grade gliomas treated?
Once the health-care team has a clear understanding of what is causing your child’s symptoms, a meeting with the team will be set up to talk about results and the treatment plan. Remember that it is helpful to bring paper and a pen or laptop and take notes at each meeting with this team. It is important to have the child’s primary caregivers in this meeting, for example both parents and additional family members if this can help. Often, a member of the team will write notes for you, and this will give you the opportunity to review these notes after the meeting.
The treatment team may include a neurosurgeon, a neuro-oncologist, radiation oncologist, a nurse practitioner or nurse, and a social worker. During the meeting, they will explain which doctor is responsible for your child’s treatment, and the roles of everyone who is there. Other team members may be involved such as a dietitian, pharmacists, occupational therapist, and physiotherapist, depending on your child’s needs. Every team member has their role in your child’s care, and everyone works together to make your child feel better.
The doctor will explain the type of tumour that your child has, based on what the team has learned through diagnostic testing. You will learn the expected effect this tumour will have on your child in the upcoming months and years, based on what is known about the tumour. This is called the prognosis.
The team may talk about placing your child on a protocol, which is a treatment plan for high-grade gliomas. You will need to consent (agree) to the plan for the treatment to begin. Teenaged patients may be asked for their consent as well.
Your team will also talk to you about placing an IV line called a central line. This will help doctors give the treatments in a safer way and avoid multiple pokes for blood tests. You will get more information about the line insertion in details during the meeting.
Supratentorial high-grade gliomas
Radiation is the main treatment for children older than three years of age. New advances in radiation therapy have allowed doctors to restrict the effects of radiation to the affected area of the brain without damaging normal surrounding brain tissue. Radiation may sometimes be combined with medications that help amplify the radiation effect. Anti-vomiting medications and sometimes steroids or a drug known as bevacizumab may be used to manage side-effects from the tumor and its treatment with radiation.
Chemotherapy does have a role in the treatment of high-grade gliomas. A combination of the medications temozolomide and lomustine (CCNU) is often used in older children. Certain tumor subtypes do not respond to temozolomide and only CCNU is used for children with those subtypes of tumour.
In children younger than 3 years old, radiation is avoided, and chemotherapy is exclusively used and includes multiple medications. The biology and behavior of high-grade gliomas in children younger than 3 is very different, and may follow a slower, less aggressive course with better survival.
In general, 2-year survival rates for children with supratentorial high-grade gliomas range from 10% to 30%.
Brainstem gliomas
For information about the treatment of this type of tumour, see the page Diffuse pontine gliomas.
Clinical trials
Many doctors are trying to make cancer treatments more successful. They can do this by studying different types of treatment, in clinical trials. Your child’s doctor may ask if you would like your child to participate in a clinical trial. You will have to sign an informed consent form for your child to participate in a trial. The health-care team will explain the differences between being on a clinical trial and getting the standard treatment.
Your child’s health-care team may recommend molecular testing to determine if your child is eligible for a clinical trial. In some cases, molecular testing results may also allow the health-care team to request newer medications for your child’s treatment.
Additional supports
When you meet with the treatment team, you may also be told about resources available to support your child, you and your other children during treatment and recovery. You will be encouraged to think about any questions concerning the diagnosis and the treatment plan.
Before you agree to the treatment offered, it is important that you understand what to expect and feel comfortable with your decision.
What is the outcome for a child with high grade glioma?
Unfortunately, despite intensive treatment, most high-grade gliomas will come back (recurrence) or continue to grow (progression). The time to recurrence is usually short, with most recurrences diagnosed within 2 years from the time of initial diagnosis. Recurrences are generally local, meaning that they occur in the same area as the original tumour. However, up to 30% of children with high-grade glioma can present with dissemination (spreading of the tumour to another area) at the time of recurrence.
Treatment at the time of recurrence depends on previous therapy:
- Infants: If there has been no previous radiation, a recurrence will be treated with surgery and radiation.
- Older children: Surgery and repeat radiation may be used, depending on when the first radiation treatment was given. Molecular tests can identify targets that can make a child eligible for clinical trials or allow the doctor to request for newer treatments like targeted and immunotherapy.
However, the overall outlook (prognosis) for these cancers remains poor. Doctors and scientists are continuing to learn more and improve the survival of children with high-grade glioma.