Childhood Brain Stem Glioma

• Childhood brain stem glioma is a disease in which benign (noncancer) or malignant (cancer) cells form in
• the tissues of the brain stem.
• Brain tumors may be benign (not cancer) or malignant (cancer).
• There are two types of brain stem gliomas in children.
• The cause of most childhood brain tumors is unknown.
• The signs and symptoms of brain stem glioma are not the same in every child.
• Tests that examine the brain are used to detect (find) childhood brain stem glioma.
• A biopsy may be done to diagnose certain types of brain stem glioma.
• Certain factors affect prognosis (chance of recovery) and treatment options.

Childhood brain stem glioma is a disease in which benign (noncancer) or malignant (cancer) cells form in the tissues of the brain stem.

Gliomas are tumors formed from glial cells. Glial cells in the brain hold nerve cells in place, bring food and oxygen to them, and help protect them from disease, such as infection.

The brain stem is the part of the brain connected to the spinal cord. It is in the lowest part of the brain, just above the back of the neck. The brain stem is the part of the brain that controls breathing, heart rate, and the nerves and muscles used in seeing, hearing, walking, talking, and eating. Most childhood brain stem gliomas are pontine gliomas, which form in a part of the brain stem called the pons.

Brain tumors are the third most common type of cancer in children.

This summary refers to the treatment of primary brain tumors (tumors that begin in the brain). Treatment for metastatic brain tumors, which are tumors formed by cancer cells that begin in other parts of the body and spread to the brain, is not discussed in this summary.

Brain tumors can occur in both children and adults; however, treatment for children may be different than treatment for adults.

Brain tumors may be benign (not cancer) or malignant (cancer):

• Benign brain tumors grow and press on nearby areas of the brain. They rarely spread into other tissues.
• Malignant brain tumors are likely to grow quickly and spread into other brain tissue. When a tumor grows into or presses on an area of the brain, it may stop that part of the brain from working the way it should. Both benign and malignant brain tumors can cause signs and symptoms and need treatment.

There are two types of brain stem gliomas in children. Childhood brain stem glioma is either a diffuse intrinsic pontine glioma (DIPG) or a focal glioma:

• DIPG is a high-grade tumor that is fast-growing and spreads all through the brain stem. It is hard to treat and has a poor prognosis (chance of recovery). Children younger than 3 years diagnosed with DIPG may have a better prognosis than children who are 3 years and older.
• A focal glioma is slow-growing and is in one area of the brain stem. It is easier to treat than DIPG and has a better prognosis.

The cause of most childhood brain tumors is unknown.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your child's doctor if you think your child may be at risk.

Possible risk factors for brain stem glioma include having certain genetic disorders, such as neurofibromatosis type 1 (NF1).

The signs and symptoms of brain stem glioma are not the same in every child. Signs and symptoms depend on the following:

• Where the tumor forms in the brain
• The size of the tumor and whether it has spread all through the brain stem
• How fast the tumor grows
• The child's age and development

Some tumors do not cause signs or symptoms. Signs and symptoms may be caused by childhood brain stem gliomas or by other conditions. Check with your child's doctor if your child has any of the following:

• Loss of ability to move one side of the face and/or body
• Loss of balance and trouble walking
• Vision and hearing problems
• Morning headache or headache that goes away after vomiting
• Nausea and vomiting
• Unusual sleepiness
• More or less energy than usual
• Changes in behavior
• Trouble learning in school

Tests that examine the brain are used to detect (find) childhood brain stem glioma.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Neurological exam: A series of questions and tests to check the brain, spinal cord, and nerve function. The
• exam checks a person’s mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro exam or a neurologic exam.
• MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the brain. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• A biopsy may be done to diagnose certain types of brain stem glioma. If the MRI scan looks like the tumor is a DIPG, a biopsy is usually not done and the tumor is not removed. If the MRI scan looks like a focal brain stem glioma, a biopsy may be done. A part of the skull is removed and a needle is used to remove a sample of the brain tissue. Sometimes, the needle is guided by a computer. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are found, the doctor will remove as much tumor as safely possible during the same surgery.

The following test may be done on the tissue that was removed:

Immunohistochemistry: A test that uses antibodies to check for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the tissue to light up under a microscope. This type of test may be used to tell the difference between brain stem glioma and other brain tumors.

The prognosis and treatment options depend on:

• The type of brain stem glioma
• Where the tumor is found in the brain and if it has spread within the brain stem
• The age of the child when diagnosed
• Whether or not the child has a condition called neurofibromatosis type 1
• Whether the tumor has just been diagnosed or has recurred (come back)

The plan for cancer treatment depends on whether the tumor is in one area of the brain or has spread all through the brain.

Staging is the process used to find out how much cancer there is and if cancer has spread. It is important to know the stage in order to plan treatment. There is no standard staging system for childhood brain stem glioma.

Treatment is based on the following:

• Whether the tumor is newly diagnosed or recurrent (has come back after treatment)
• The type of tumor (either a diffuse intrinsic pontine glioma or a focal glioma)

Recurrent Childhood Brain Stem Glioma

A focal brain stem glioma may recur many years after first being treated. The tumor may come back in the brain or in other parts of the central nervous system. Before cancer treatment is given, imaging tests, a biopsy, or surgery may be done to make sure there is cancer and find out how much cancer there is.

There are different types of treatment for children with brain stem glioma. Different types of treatment are available for children with brain stem glioma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with brain stem glioma should have their treatment planned by a team of health care providers who are experts in treating childhood brain tumors.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatric health care providers who are experts in treating children with brain tumors and who specialize in certain areas of medicine. These may include the following specialists:

• Pediatrician
• Neurosurgeon
• Neuropathologist
• Radiation oncologist
• Neuro-oncologist
• Neurologist
• Rehabilitation specialist
• Neuroradiologist
• Endocrinologist
• Psychologist

Childhood brain stem gliomas may cause signs or symptoms that begin before the cancer is diagnosed and continue for months or years. Childhood brain stem gliomas may cause signs or symptoms that continue for months or years. Signs or symptoms caused by the tumor may begin before diagnosis. Signs or symptoms caused by treatment may begin during or right after treatment.

Some cancer treatments cause side effects months or years after treatment has ended. These are called late effects. Late effects may include the following:

• Physical problems
• Changes in mood, feelings, thinking, learning, or memory
• Second cancers (new types of cancer)

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the effects cancer treatment can have on your child. Six types of standard treatment are used:

Surgery

Surgery may be used to diagnose and treat childhood brain stem glioma.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the cancer.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type of the cancer being treated. External radiation therapy is used to treat DIPG. External and/or internal radiation therapy may be used to treat focal brain stem gliomas.

Several months after radiation therapy to the brain, imaging tests may show changes to the brain tissue. These changes may be caused by the radiation therapy or may mean the tumor is growing. It is important to be sure the tumor is growing before any more treatment is given.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly in the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type of the cancer being treated.

Because radiation therapy to the brain can affect growth and brain development in young children, clinical trials are studying ways of using chemotherapy to delay or reduce the need for radiation therapy.

Cerebrospinal fluid diversion

Cerebrospinal fluid diversion is a method used to drain fluid that has built up in the brain. A shunt (long, thin tube) is placed in a ventricle (fluid-filled space) of the brain and threaded under the skin to another part of the body, usually the abdomen. The shunt carries extra fluid away from the brain so it may be absorbed elsewhere in the body.

Observation

Observation is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Some focal brain stem gliomas that cannot be removed by surgery may be treated with BRAF kinase inhibitor therapy. BRAF kinase inhibitors block the BRAF protein. BRAF proteins help control cell growth and may be mutated (changed) in some types of brain stem glioma. Blocking mutated BRAF kinase proteins may help keep cancer cells from growing.

New types of treatment are being tested in clinical trials. Information about clinical trials is available from the NCI website. Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment. Clinical trials are taking place in many parts of the country.

Follow-up tests may be needed:

• Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.
• Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
• If the results of imaging tests done after treatment show a mass in the brain, a biopsy may be done to find out if it is made up of dead tumor cells or if new cancer cells are growing. In children who are expected to live a long time, regular MRIs may be done to see if the cancer has come back.

Newly Diagnosed Childhood Brain Stem Glioma

Newly diagnosed childhood brain stem glioma is a tumor for which no treatment has been given. The child may have received drugs or treatment to relieve signs or symptoms caused by the tumor.

Standard treatment of diffuse intrinsic pontine glioma (DIPG) may include the following:

• Radiation therapy
• Chemotherapy (in infants)

Standard treatment of focal glioma may include the following:

• Surgery that may be followed by chemotherapy and/or radiation therapy
• Observation for small tumors that grow slowly
• Cerebrospinal fluid diversion may be done when there is extra fluid in the brain
• Internal radiation therapy with radioactive seeds, with or without chemotherapy, when the tumor cannot be removed by surgery
• Targeted therapy with a BRAF kinase inhibitor, for certain tumors that cannot be removed by surgery
• Treatment of brain stem glioma in children with neurofibromatosis type 1 may be observation (the tumors are slow-growing in these children and may not need specific treatment for years)

Talk with your child's doctor about clinical trials that may be right for your child.

Progressive or Recurrent Childhood Brain Stem Glioma

When cancer does not get better with treatment or comes back, palliative care is an important part of the child's treatment plan. It includes physical, psychological, social, and spiritual support for the child and family. The goal of palliative care is to help control symptoms and give the child the best quality of life possible. Parents may not be sure about whether to continue treatment or what kind of treatment is best for their child. The healthcare team can give parents information to help them make these decisions.

There is no standard treatment for progressive or recurrent diffuse intrinsic pontine glioma. The child may be treated in a clinical trial of a new treatment.

Treatment of recurrent focal childhood brain stem glioma may include the following:

• A second surgery to remove the tumor
• External radiation therapy
• Chemotherapy
• A clinical trial of a new treatment