High-Grade Glioma

What is high-grade glioma (HGG)?

High-grade gliomas (HGG) are aggressive tumors of the brain and/or spinal cord that grow rapidly and can spread into nearby brain tissue. In children, they are most often seen between the ages of 5 years and 15 years.

HGG is very difficult to treat. Standard treatment includes surgery, radiation therapy, and chemotherapy. Families may want to consider clinical trials that test new treatments.

The average 5-year survival rate for high-grade glioma varies by the molecular subtype and generally ranges from <10% to 20%. Early palliative care is helpful to ease symptoms and support a better quality of life.

Symptoms of high-grade glioma

The symptoms of high-grade glioma depend on:

• Size of the tumor
• Location of the tumor
• Age of the child
• How fast the tumor grows

Signs and symptoms of high-grade glioma may include:

• Headaches, especially in the early morning
• Nausea and vomiting
• Vision, hearing, or speech problems
• Loss of balance or problems walking
• Handwriting problems
• Weakness, tingling, or changes in the way the body feels on 1 side
• Unusual sleepiness
• Changes in energy level
• Changes in mood, personality, behavior, memory, or thinking
• Seizures
• Weight gain or loss for unknown reason
• Increased head size (in infants)

Risk factors for high-grade glioma

Most pediatric high-grade gliomas happen randomly, but some factors may increase the risk. However, these factors are rare, and most children with high-grade glioma do not have any of them.

Inherited conditions

Certain inherited conditions can make a child more likely to develop brain tumors, including high-grade gliomas. These conditions include:

• Li-Fraumeni syndrome (LFS): Li-Fraumeni syndrome or LFS is a rare condition that increases the risk of developing different types of cancer, often at a young age, due to changes in a gene called p53 that helps control cell growth. HGG is a tumor type that can be seen as part of LFS.
• Neurofibromatosis type 1 (NF1): Neurofibromatosis type 1 or NF1 is a genetic condition that can cause skin changes, tumors on nerves, and other health problems. People with NF1 have an increased risk of developing HGG.
• Mismatch repair syndrome: Mismatch repair syndrome is a rare genetic condition that increases the risk of certain cancers because the body has trouble fixing mistakes in DNA.

Past radiation therapy to the brain also increases the risk of developing HGG.

Diagnosis of high-grade glioma

Tests to diagnose high-grade glioma include:

• A physical exam and health history to learn about symptoms, general health, past illness, and risk factors.
• A neurological exam to assess brain function. This includes memory, vision, hearing, muscle strength, balance, coordination, and reflexes.
• Imaging tests to help identify the tumor, its size, and location. Magnetic resonance imaging (MRI) is the main imaging test. An MRI is also done after surgery to see if any tumor remains.
• A biopsy or a surgical resection in which surgeons remove tumor sample. A pathologist looks at it under a microscope to identify the type and grade of the tumor.
• Genetic testing of the tumor to find specific changes (mutations) to identify the type of tumor and show possible targets for treatment. Gene changes linked to high-grade glioma include BRAF V600E, NTRK, ALK, and ROS1.

Types of high-grade glioma 

Types of high-grade glioma include:

• Diffuse midline glioma
• Diffuse hemispheric glioma
• Diffuse pediatric-type high-grade glioma
• Infant-type hemispheric glioma

Other names for specific types of high-grade glioma include:

• Adult-type diffuse glioma
• Anaplastic astrocytoma
• Anaplastic oligodendroglioma
• Astrocytoma, IDH mutant, grade 3 or grade 4
• Brainstem glioma
• Diffuse hemispheric glioma, H3 G34-mutant
• Diffuse intrinsic pontine glioma (DIPG)
• Diffuse midline glioma, H3 K27M-mutant
• Diffuse pediatric-type high grade glioma, H3 wildtype and IDH wildtype
• Diffuse pediatric-type high grade glioma, NOS
• Giant cell glioblastoma
• Glioblastoma
• Gliomatosis cerebri
• Pleomorphic xanthoastrocytoma
• Oligodendroglioma

Recurrent glioma

Recurrent glioma happens when a glioma returns after treatment. It can grow in the same spot or in other parts of the brain or spinal cord. Sometimes, low-grade glioma can come back as a high-grade tumor. Doctors use tests to find out if the cancer has returned and where it is. Treatment for recurrent glioma depends on where the tumor has come back.

Grading and staging of high-grade glioma

Staging is how doctors figure out the spread of cancer in the body. This helps them decide the best treatment. In high-grade glioma, it is achieved by MRI of the brain and MRI of the spine.

Tumor grading describes:

• How different the cancer cells look compared to normal cells
• How fast the tumor might grow and spread in the brain or spinal cord
• How likely the tumor is to come back after treatment
• The genetic changes that cause the tumor to develop

High-grade gliomas grow fast and are graded 3 or 4. They often spread within the brain and spinal cord. The grade helps doctors predict how the tumor will behave and plan treatment.

Treatment of high-grade glioma

Treatment depends on the type of tumor, its location, and whether it has spread or has come back.

Surgery for high-grade glioma

Surgery to remove as much of the tumor as possible is the main treatment for high-grade glioma. But if the tumor is in a sensitive area like the brainstem, surgeons may not be able to remove all of it. Even partial removal can help reduce symptoms and improve outcomes.

Radiation therapy for high-grade glioma

Radiation therapy is a key part of treatment for high-grade glioma. Proton beam radiation may be an option.

Radiation therapy is usually avoided in patients aged 3 and younger. This is because of possible serious damage to the brain while it is still developing.

Chemotherapy for high-grade glioma

Chemotherapy may be combined with radiation. Chemotherapy drugs may include:

• Temozolomide during radiation therapy
• Temozolomide and lomustine after radiation therapy has completed

Patients with mismatch repair deficiency usually do not get temozolomide or lomustine because they are alkylating agents. Alkylating agents are generally not effective in patients with mismatch repair deficiency.

Targeted therapy for high-grade glioma

Targeted therapies work by acting on, or targeting, certain features of tumor cells. These drugs change signals and processes that cancer cells use to grow, divide, and send messages to other cells. Stopping these activities helps kill cancer cells.

For tumors that involve BRAF V600E changes, patients may get medicine known as MEK inhibitors, such as dabrafenib and trametinib. Patients will get these medicines after radiation instead of traditional chemotherapy.

Patients with mismatch repair deficiency may get drugs such as pembrolizumab and nivolumab after completing radiation therapy.

Targeted therapy drugs such as entrectinib and lorlatinib are under study for fusion-positive (NTRK, ALK, ROS1) pediatric high-grade gliomas.

Prognosis for high-grade glioma

The outlook for children with high-grade gliomas is poor, and it depends on many factors. These include the type of tumor, its location, and whether it has specific genetic changes.

The 5-year survival rate for high-grade glioma is <10% to 20%. The average survival time is about 18 months. Families may consider clinical trials that test new treatments to see if outcomes can be improved.

Your child’s doctor is the best source of information about prognosis.

Every child is different. New treatments are being developed. Advances in research are giving families more options and hope for the future.

Support for patients with high-grade glioma

Caring for a child with a high-grade glioma can be overwhelming, but you don’t have to face it alone. Your child’s care team will work together to provide the best care possible.

Care team members such as psychologists, social workers, and chaplains can provide mental, emotional, and spiritual health support. Palliative care professionals can help manage symptoms and help make each day the best it can be.

Your child’s care team can help create a plan for ongoing care.

Questions to ask your care team

• What are the treatment options for my child's specific type of glioma?
• What are the potential risks and benefits of each treatment option?
• What supportive care or palliative care options can help my child's comfort and well-being?
• Are there any clinical trials or new treatments that might be suitable for my child?
• How might treatment affect my child's thinking, learning, emotional, and physical development?
• What support services are available for my child and family?