All About Pediatric Gliomas (Low and High Grade)

What is a Pediatric Glioma?

A glioma is a type of tumor in the brain or spinal cord. Gliomas start in the glial cells. When a child has a glioma, it is called “pediatric glioma.”

A glial cell is a type of cell in the brain that surrounds the neurons. Neurons are the cells that make electrical impulses to transmit information. Glial cells support and insulate neurons. For example, an astroctye is a special form of glial cell. Astrocytomas are a type of glioma that forms because of abnormal growth of astrocytes.

Gliomas can be found in any part of the brain or spinal cord. About 60% of brain tumors in children occur in the infratentorial brain. They can also occur in the supratentorial brain.

• The infratentorial brain is the lower part of the brain near the middle of the back of the head and includes the cerebellum and the brainstem. This is the part of the brain that controls movement and balance.
  • The cerebellum is the part of the brain at the back of the skull. It controls voluntary muscle movements, like posture, speech, balance, and coordination.
  • The brainstem is the middle of the brain and connects the brain to the spinal cord. The brainstem controls breathing, movement of the eyes, passing on information about sensation and involuntary muscle movements.
• The supratentorial brain is the part of the brain that is above the cerebellum. The supratentorial brain includes the cerebrum, which is the largest part of the brain.
  • The cerebrum controls thinking, emotions, problem-solving, learning, talking, reading, writing, and voluntary movement.

What causes Glioma and who is at risk?

Gliomas are the most common type of brain tumor in both children and adults. About 3,540 brain and other CNS tumors will be diagnosed this year in children aged 0-14.

In most cases, we do not know why children develop brain tumors. There are some syndromes or genetic mutations that we know increase a child’s risk of developing a glioma. These syndromes include Li-Fraumeni syndrome, Turcot syndrome, and neurofibromatosis. Children with neurofibromatosis are specifically at higher risk for developing optic pathway gliomas. Another syndrome, tuberous sclerosis, can also lead to an increased risk of a type of low-grade glioma called subependymal giant cell astrocytoma.

Sometimes children who have been treated for other types of cancer can develop brain tumors as a secondary cancer. In most cases, however, we do not know why a patient develops a brain tumor. When a tumor develops in the brain, you cannot see it growing. Usually, patients do not know that they have a brain tumor until the tumor is large enough to cause symptoms by pushing on normal structures in the brain.

How can glioma be prevented in a child?

Children who are diagnosed with glioma often do not have any risk factors. Because of this, there is no way to prevent glioma.

What screening tests are used?

There are no recommended screening tests for childhood cancer. A child won't be tested for glioma unless they are showing signs or symptoms of the disease.

What are the signs and symptoms of gliomas?

When brain tumors grow, they press on the normal parts of the brain and cause them to stop working properly. The signs and symptoms of a brain tumor depend on where the tumor is located in the brain. Gliomas can occur in any part of the CNS. Usually, you cannot tell from the symptoms exactly what type of brain tumor is causing the problems.

The most common symptoms of a glioma are:

• Headaches, especially ones that wake children up in the morning or headaches that get better after vomiting.
• Nausea, with or without vomiting (throwing up). It is a concern if the child has severe and frequent vomiting that does not seem to be part of a gastrointestinal bug (stomach bug).

Other symptoms of a brain tumor are:

• Changes in vision, such as double vision or blurry vision, hearing, or speech.
• If the tumor is in the optic pathway, it is more common to have vision loss or a bulging appearance to the eye (this is called proptosis).
• Children with brain tumors may become less steady while walking or have difficulty with balance. This is especially common in patients with astrocytomas because they often occur in the infratentorial brain.
• Children may become clumsy or have trouble holding objects or writing.
• Children may be confused or be more sleepy than normal.
• A child’s behavior may change if he or she has a brain tumor, including being irritable, and some young children do not meet their developmental milestones.
• In some cases, the first sign of a brain tumor is a seizure.
• In infants, sometimes the head will get visibly larger if a baby develops a brain tumor.

Children with high-grade gliomas tend to have symptoms for a shorter period of time because these tumors grow more quickly.

How is Glioma Diagnosed?

History and Physical examination– The first step in diagnosing a glioma is physical exam and overview of the child’s health history. Healthcare providers ask many questions about changes in the child and about all of the signs and symptoms discussed above. They will ask if any other members of the family have had a brain tumor or any other cancer because there are some types of cancer that tend to run in families. The provider will perform a full physical examination, including a neurologic examination. The neurologic examination tests the functioning of the brain and the spinal cord to look for any abnormalities. The neurologic examination will include checking a child’s mental status, coordination, senses, and reflexes. If a child is old enough to walk, they will check if the child is walking normally.

Imaging– Brain tumors are diagnosed by seeing the tumor on imaging of the brain. The two main kinds of imaging are:

• Computed Tomography (CT) Scan- Use x-rays to take a series of pictures of the brain from different angles. CT scans are very quick. Sometimes dye will be injected into the vein before the CT scan is performed to help improve the picture. A CT scan will often be the first type of imaging performed because it takes less time to do the test. If a CT scan shows a brain tumor, a patient will then have an MRI.
• Magnetic Resonance Imaging (MRI)- MRI scans use magnets to take a detailed picture of the brain from multiple angles. A chemical called gadolinium is injected into the vein before the MRI. Gadolinium helps certain areas of the brain light up in the images to help with the diagnosis. An MRI scan can take multiple hours and the child needs to stay completely still during the scan. Sometimes children need medications to make them sleepy in order to not move during an MRI scan.
  A brain tumor will look like a mass or lesion in the brain that does not look like the normal brain tissue on the CT scan or MRI. Depending on the type of tumor, sometimes an MRI scan of the spine will need to be done to look for spread of the tumor, called metastasis, to other parts of the body.

Biopsy – The best way to make a final diagnosis about the type of brain tumor is by looking at the tumor cells under a microscope to evaluate for cancer. In order to do this, surgery needs to be done to take a piece of the tumor out of the brain. This is called a biopsy. Specially trained doctors called pathologists will look at the tumor cells under a microscope to make a diagnosis of what the tumor is. Often the diagnosis is made when the whole tumor is removed during surgery instead of having a separate biopsy. Sometimes a brain tumor is located in a part of the brain where doing surgery would cause more problems than removing the brain tumor would solve. In those cases, the diagnosis is made based on the MRI results and treatment is planned based on this imaging.

Lumbar Puncture (LP) – Children with high-grade gliomas may need a lumbar puncture (spinal tap) to look for spread of tumor to the spinal fluid (CSF). A lumbar puncture is when a needle is inserted into the lower back to get a sample of the spinal fluid. A pathologist will look at the cells from the CSF to look for any evidence of tumor.

How is glioma staged?

Staging is often used in cancer to help create a treatment plan. Staging takes into account how large a tumor is, how it looks under a microscope and if it has spread. There is no standard staging system for glioma but it is given a grade. Grading is done based on World Health Organization (WHO) criteria. The grade is a measure of how abnormal the tumors cells look under the microscope.

• High-grade tumors look very unusual.
• Low-grade tumors look different than normal brain cells, but they are not as abnormal-appearing as high-grade tumor cells.

The grade of the tumor also relates to how fast the tumor grows. The WHO criteria were modified in 2016, and many gliomas are now classified both by their name, and by a description of their molecular or genetic characterization.

Types of High Grade Gliomas are:

Anaplastic astrocytoma – This is a high-grade (WHO grade III) tumor. It is called anaplastic because the cells of the tumor do not have the structure of normal brain glioma cells. These tumors can grow in any part of the CNS. These tumors grow faster than low-grade gliomas and are more likely to recur even after treatment. They usually do not spread to other parts of the CNS.

Glioblastoma multiforme – This is a high-grade (WHO grade IV) tumor. These tumors can occur anywhere in the brain or spinal cord. While the tumors may start in one part of the brain, they sometimes spread to other areas in the CNS. These tumors are more aggressive, which means they grow faster than low-grade gliomas, and they also may grow back even after treatment.

Diffuse midline glioma, H3 K27M-mutant (formerly called diffuse intrinsic pontine glioma (DIPG) – This is a high-grade tumor that is found in the brainstem. These tumors account for 10% of all brain tumors in children. Patients with these tumors usually have neurologic changes that lead them to be diagnosed with their brain tumors.

Types of Low Grade Gliomas are:

Pilocytic astrocytoma – This is a low-grade (WHO grade I) brain tumor that is made up of cells that are spindle-like in appearance. Pilocytic astrocytoma is the most common type of low-grade glioma. These types of gliomas often occur in the cerebellum and are called cerebellar pilocytic astrocytomas, though they can occur in any part of the CNS. The most common type of pilocytic astrocytoma is a juvenile pilocytic astrocytoma (JPA). JPA makes up 20% of pediatric brain tumors. Low-grade astrocytomas are usually slow-growing and are not found until they are very large and cause problems because of their size.

Optic pathway glioma – This is a low-grade tumor that occurs in the optic nerve. The optic nerve is the nerve that goes to the eye.

Tectal glioma – This is a low-grade tumor that occurs near the brainstem.

Oligodendroglioma – This is a very rare type of low-grade glioma.

Ganglioglioma – This is a low-grade glioma. It has some features that look like glial cells and some features that look like neurons.

Pleomorphic xanthoastrocytoma – This is a low-grade glioma. The tumor often has a cyst as part of the tumor. Pleomorphic xanthoastrocytomas most often grow in the temporal lobe of the brain.

When a child is diagnosed with a glioma, the histology, location and classification of the tumor will help guide the treatment of the tumor.

How are pediatric gliomas treated?

Treatment for pediatric glioma will depend on many factors, including the age of the child, the type of glioma being treated, the symptoms the child is having, and the goals of treatment. More than one treatment may be used.

The main options for treating brain tumors include surgery to remove the tumor, radiation and chemotherapy. If a child does not have symptoms from a tumor that is a low-grade glioma, sometimes the patient will be monitored closely and will not undergo treatment. The patient, caregivers and care team will discuss the best course of treatment.

Surgery

If the provider thinks that a mass found in the brain on CT or MRI scan is a glioma, a surgeon will do a biopsy or surgery to remove the tumor. The main treatment for both high and low-grade gliomas is surgery to remove (resect) as much of the tumor as can be taken out safely. Surgeons who remove brain tumors are called neurosurgeons. The neurosurgeon will use the CT or MRI scan to choose the surgical plan. The neurosurgeon may not know how much of the tumor can be safely removed until he or she sees what the brain tumor looks like during the surgery.

A gross total resection is when the whole tumor is removed during the surgery and no remaining tumor can be seen either during surgery or on MRI. A near-total resection is when more than 90% of the tumor is removed during surgery. A sub-total resection is when 51-90% of the tumor is removed during surgery. A partial resection is when 10-50% of the tumor is removed during surgery.

The goal of surgery is to resect as much of the tumor as possible. However, studies have shown that it is not enough to just do surgery. Most patients need chemotherapy and/or radiation to fully treat their brain tumors. Sometimes brain tumors are located in parts of the brain where doing surgery would cause more problems. This is the case in most optic gliomas and brainstem gliomas. In those cases, children may not have surgery and are treated with radiation and/or chemotherapy.

Radiation Therapy

Radiation therapy uses x-rays or high- energy particles that are directed at a tumor to kill abnormal cells. The dose of radiation will depend on the type of tumor, the location of the tumor, and the age of the child. Radiation can have side effects, specifically causing long-term development problems in children who are very young. Radiation therapy is often delayed as long as possible in the youngest children to give them a chance to grow and develop before receiving radiation.

There are two main types of radiation therapy that can be used:

1. Photon radiotherapy: The traditional form of radiation therapy. Photon therapy refers to the use of x-rays that are aimed at the tumor, enter the body, travel through the tumor, and then exit from through the other side of the body. This means that the tissues on either side of the tumor are treated with radiation, in addition to the tumor itself.
2. Proton radiotherapy: Proton therapy is different than photon therapy. Protons enter the body and are at their peak dose at the site of the tumor. This means that they do not give as much radiation to the tissues on either side of the tumor. This can be very helpful when radiation is given to an important part of the body, such as the brain. Only some cancer centers are able to use proton therapy.

Chemotherapy

Chemotherapy is medicine that is used to treat cancer. Chemotherapy can be given by mouth, into a vein (IV), into the muscle or into the spinal fluid. After surgery, children with high-grade gliomas will often receive chemotherapy in addition to radiation therapy. Some children will receive chemotherapy before surgery to shrink the tumor and make it possible to remove more of the tumor. The chemotherapy agents that are currently used in treating high-grade gliomas are vincristine, carboplatin, temozolamide, lomustine, vorinostat, bevacizumab and irinotecan. Some children with low-grade gliomas whose tumors cannot be removed surgically will receive chemotherapy as well.

Immunotherapy

Immunotherapy medications use the body's own immune system to kill cancer cells. The provider may do laboratory tests to identify the genes, proteins, and other traits of the tumor and recommend immunotherapy. An example of a type of immunotherapy being used for glioma is a “monoclonal antibody.” One kind of monoclonal antibody is a medication called bevacizumab. Bevacizumab works by blocking a certain protein on the tumor cells and slowing the growth of the tumor.

Treatment of specific types of gliomas

Low-grade gliomas (pilocytic astrocytoma and fibrillary astrocytoma) – For patients with low-grade gliomas, surgery may be the only treatment that is needed. If a child has a gross total resection, he or she does not need any other treatment. If there is not a gross total resection or if the tumor grows after surgery, a child may need radiation or chemotherapy. This decision will be made based on how much of the tumor remains, the post-operative symptoms of the child, and the age of the child.

High-grade gliomas (anaplastic astrocytoma and glioblastoma multiforme) – Most patients with high-grade gliomas have at least part of their tumor removed during surgery. For some patients, however, the tumor cannot be fully removed safely. Children with high-grade gliomas need additional treatment after surgery due to the aggressive nature of the tumor. This additional therapy is to treat remaining tumor cells that are presumed to be present even after surgery. Most children will have high-dose radiation therapy to the tumor site after surgery. This radiation is usually given over a 6 week period and is combined with weekly chemotherapy. Children often receive further maintenance chemotherapy after radiation is completed.

Optic pathway glioma – While these are low-grade tumors, the location of these tumors in the optic pathway can make it difficult to surgically remove the tumor without causing many long-term side effects. These patients receive a combination of chemotherapy agents to treat their tumors.

Some children who have recurrent glioma (glioma that keeps coming back) will receive high-dose chemotherapy followed by autologous stem cell transplant. Other children may receive treatment as part of a phase I clinical trial evaluating new chemotherapy options.

Clinical Trials

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of diseases. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

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. Unfortunately, gliomas can recur (come back) after treatment. If the tumor recurs, the plan for treatment will be very customized, and will depend on where the new tumor is and how the child was treated before.

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.

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 follow up care (an oncologist, survivorship doctor or primary care doctor). Talk with the team about developing a survivorship care plan or develop one using the Smart ALACC tool. Your child may benefit from being seen in a survivorship clinic. At a survivorship clinic a provider can review your child's 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 on  OncoLink's survivorship clinic list.

Resources for More Information

National Brain Tumor Society

Aim to improve understanding of all brain tumors and transform research into new and effective treatments, as quickly as possible. Offers brain tumor information, related news and a blog.

http://braintumor.org/

American Brain Tumor Association

Providing comprehensive resources that support the complex needs of brain tumor patients and caregivers, as well as the critical funding of research in the pursuit of breakthroughs in brain tumor diagnosis, treatment and care.

http://www.abta.org

Pediatric Brain Tumor Consortium: research organization devoted to the study of tumor biology and new therapies for primary CNS tumors of childhood.

Pediatric Brain Tumor Foundation