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Glioblastoma multiforme

  • A high-grade glioma is a malignant tumor that arises from the brain’s glial cells, which nourish and support neurons. There are two high-grade gliomas: glioblastoma multiforme (grade IV glioma) and anaplastic astrocytoma (grade III glioma). These are aggressive tumors that rapidly infiltrate adjacent healthy brain tissue and, as a result, are difficult to treat.

    As you read on, you’ll find detailed information about glioblastoma multiforme and anaplastic astrocytoma. If you would like to read more general information about brain tumors first, see our overview on brain tumors.

    How Dana-Farber/Boston Children’s Cancer and Blood Disorders Center approaches glioblastoma multiforme and anaplastic astrocytoma

    Your child will be seen by specialists and caregivers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, an integrated pediatric oncology program through Dana-Farber Cancer Institute and Boston Children’s Hospital that provides—in one specialized program—all the services of both a leading cancer center and a leading pediatric hospital. Dana-Farber/Boston Children’s is a world-renowned destination for children with malignant and non-malignant brain and spinal cord tumors.

    Most children diagnosed with glioblastoma multiforme or anaplastic astrocytoma receive surgery and radiation, and in some cases chemotherapy. Our pediatric neuro-oncology and pediatric neurosurgical specialists at Dana-Farber/Boston Children’s Pediatric Brain Tumor Center offer:

    • technological advances, such as the intra-operative MRI, which allow our pediatric neurosurgeons to “see” the tumor as they operate with MRI scans
    • treatment with the best standard of care, including neurosurgery, radiation therapy and chemotherapy
    • access to unique Phase I clinical trials
  • What is glioblastoma multiforme or anaplastic astrocytoma?

    Glioblastoma multiforme (GBM) and anaplastic astrocytomas (AA) are types of brain tumors—masses of tissue that develop from abnormally growing cells.  GBM and AA arise from a certain kind of brain cell known as a glial cell—for this reason, they may also be known as "gliomas."

    The specific kind of glial cell that they come from is called an astrocyte, and this is why they can also be called "astrocytomas." Both GBM and AA are malignant tumors, meaning that they grow and metastasize, or spread.  GBM tend to be more aggressive than AA.

    What’s the difference between glioblastoma multiforme and anaplastic astrocytomas?

    When doctors diagnose a brain tumor, they “stage” it, or give it a grade, according to whether it has spread, and if so, how far. This helps us determine treatment options and prognosis. The World Health Organization classification scheme includes four grades of glioma:

    Low-grade gliomas

    High-grade gliomas

    Glioblastoma multiforme is a grade IV tumor. These are aggressive tumors that spread to adjacent healthy brain tissue.

    Anaplastic astrocytoma is a grade III tumor. They grow less rapidly than glioblastoma multiforme, but are equally malignant.

    Where do glioblastoma multiforme and anaplastic astrocytoma occur?

    GBM and AA can occur in different parts of the brain. Depending on the size and location of the tumor, children may experience different symptoms.

    • About 65 percent of these tumors arise in the cerebral hemispheres, which control many higher functions such as speech, movement, thought and sensation.
    • They also can occur in the part of the brain that identifies sensations such as temperature, pain and touch and the region of the brain that controls balance and motor function.

    These tumors are usually diagnosed between the ages of 5 and 9, and occur in boys and girls equally.

    What causes a glioblastoma multiforme and anaplastic astrocytoma? 

    High-grade gliomas like GBM and AA occur without an identifiable cause in most patients. However, these tumors can occur with increased frequency in families with certain hereditary conditions, including:

    Signs & Symptoms

    What are symptoms of a glioblastoma multiforme and anaplastic astrocytoma?

    Each child may experience symptoms differently, and they vary greatly depending on the size and location of the tumor and whether it has spread.

    GBM and AA can cause symptoms that result from increased pressure within the head, as well as other symptoms related to the tumor’s specific location, rate of growth and associated inflammation.

    Symptoms can develop slowly over time or begin very suddenly. The following are the most common:

      • headache and lethargy (generally upon awakening in the morning)
      • seizures, depending on tumor type and location
      • compression of surrounding brain structures. Depending on the location, this can cause:
        • weakness and other motor dysfunction
        • hormonal abnormalities
        • changes in behavior or thought processes
  • In addition to a physical exam, a medical history and neurological exam (a test of your child’s reflexes, muscle strength, eye and mouth movement, coordination and alertness), your child's physician also may order the following tests for pediatric brain tumors:

    • magnetic resonance imaging (MRI): to produce detailed images of the brain and spine
    • magnetic resonance spectroscopy (MRS): A test done along with MRI at specialized facilities that can help identify tissue as either normal or tumorous, which may be able to distinguish between different types of tumors.
    • computerized tomography scan (a CT or CAT scan): to capture a detailed view of the body, and particularly helpful in examining bones and cerebral spinal fluid.
    • positron emission tomography (or PET) scan: These scans measure the use of glucose (blood sugar) within organs and tissues. Tumors use glucose more quickly than normal tissues, causing them to show up brightly on these scans.
    • biopsy or tissue sample: This sample is taken from the tumor to provide definitive information about the type of tumor. This is collected during surgery.
    • lumbar puncture (spinal tap): to remove a small sample of cerebrospinal fluid (CSF) and determine if any tumor cells have started to spread into this fluid

    After we complete all necessary tests, our experts meet to review and discuss what they have learned about your child's condition. Then, we will meet with you and your family to discuss the results and outline the best pediatric brain tumor treatment options.

  • Children with glioblastoma multiforme or anaplastic astrocytomas are treated through the Glioma Program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, an integrated pediatric hematology and oncology partnership between Dana-Farber Cancer Institute and Boston Children’s Hospital. Working together, we provide more specialists, more programs, and more clinical trials than almost any other pediatric center treating cancer and blood disorders in the world.

    There are a number of treatments we may recommend. Some of them help to treat the tumor, while others address complications of the disease or side effects of the treatment.

    The primary treatment for newly-diagnosed GBM and AA includes:

    Surgery for brain tumor removal

    The first treatment is usually surgery to remove as much of the tumor as possible, ideally using advanced techniques, such as intraoperative MRI (where surgeons can visualize the tumor as they operate with MRI scans), to maximize tumor removal.

    • Pediatric neurosurgery has multiple roles in the management of childhood glioblastoma multiforme and anaplastic astrocytoma, including treatment of increased intracranial pressure, biopsy and tumor removal.
    • Complete resection or surgical removal of the entire tumor is ideal when possible, though most high-grade gliomas cannot be completely removed because they tend to infiltrate into adjacent healthy tissues.
    • In general, the more completely the tumor can be removed, the greater the chances for survival.

    Radiation therapy

    Your child also may receive precisely targeted and dosed radiation to kill cancer cells left behind after surgery. This is important to control the local growth of tumor, and it helps increase survival in high-grade gliomas.

    Chemotherapy

    Chemotherapy refers to drugs that interfere with the cancer cells' ability to grow or reproduce. To date, no chemotherapy regimen has been demonstrated to increase survival rates in children with GBM or AA, though, chemotherapy before surgery may help shrink the tumor, making it possible to remove.

    • Different groups of chemotherapy drugs work in different ways to fight cancer cells and shrink tumors.
    • Often, we use a combination of chemotherapy drugs.
    • We may give certain chemotherapy drugs in a specific order.
    • A variety of chemotherapy regimens have been tested in the treatment of newly diagnosed high-grade gliomas.
    • Studies in adults have suggested that certain drugs can produce modest responses in high-grade gliomas, but they have less effect in children.
    • Several treatment regimens have produced responses, none have improved survival. Nor has the use of high-intensity chemotherapy (which, because it destroys a patient's bone marrow) is used in conjunction with what is called an autologous stem cell transplant.
    • New methods that specifically target or stimulate an immune response against newly diagnosed GBM and AA tumors are now being tested.

    Chemotherapy is systemic treatment, meaning it is introduced to the bloodstream and travels throughout the body to kill cancer cells. Chemotherapy can be given:

    • orally, as a pill to swallow
    • intramuscularly (IM), as an injection into the muscle or fat tissue
    • intravenously (IV), directly to the bloodstream
    • intrathecally, with a needle directly into the fluid surrounding the spine

    How are side effects of brain tumor treatment in children managed?

    There can be many adverse side effects during the treatment of glioblastoma multiforme and anaplastic astrocytoma. Knowing what these side effects are can help you, your child and your care team prepare for, and, in some cases, prevent these symptoms from occurring.

    • Radiation therapy often produces inflammation, which can temporarily worsen symptoms and dysfunction. To control this, inflammation steroids are sometimes necessary.
    • Chemotherapy drugs cannot tell the difference between normal healthy cells and cancer cells. Some of chemotherapy agents are associated with fatigue, diarrhea, constipation and headache. These side effects can be effectively managed under most circumstances with standard medical approaches.

    Our Pediatric Brain Tumor Center also has access to specialists who deliver complementary or alternative medicines. These treatments, which may help control pain and side effects of therapy, include the following.

    • acupuncture/acupressure
    • therapeutic touch
    • massage
    •  herbs
    • dietary recommentdations

    Talk to your child's physician about whether complementary or alternative medicine might be a viable option.

    What is the expected outcome after treatment for glioblastoma multiforme or anaplastic astrocytoma?

    Unfortunately, the prognosis for GBM and AA tumors remains very poor. In general, more complete removal of tumors, when possible, results in a greater chance of survival. Your child’s physician will discuss treatment options with you, including experimental clinical trials, and supportive care.

    What about progressive or recurrent disease?

    Unfortunately, the prognosis for GBM and AA remains very poor. In general, more complete surgical removal of the tumor, when possible, results in greater chance of survival. In some instances, experimental clinical trials can be an option.

    Resources and support

    There are also a number of patient and family support services at Dana-Farber/Boston Children's to help you and your family through this difficult time.

    When appropriate, our Pediatric Advanced Care Team (PACT) offers supportive treatments intended to optimize the quality of life and promote healing and comfort for children with life-threatening illness. PACT also can provide psychosocial support and help arrange end-of-life care when necessary.

  • Clinical innovations

    The pediatric neurosurgeons at Dana-Farber/Boston Children's Cancer and Blood Disorders Center have access to the most recent technological advances, including high-tech imaging, such as PET, CT and functional MRI, which enables us to understand exactly where the tumor tissue is and to map out surgeries and treatments that minimize risk to healthy brain tissue.

    For children experiencing seizures, our pediatric neurologists expertly use electroencephalograms (EEGs) to determine the source of seizure activity. They work closely with neurosurgeons to ensure that healthy tissue responsible for everyday functions, such as speech and movement, are minimally damaged during surgery.

    What is the latest research on malignant gliomas, including glioblastoma multiforme?

    Clinical and basic scientists at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center are conducting numerous research studies to help clinicians better understand and treat malignant gliomas.

    We belong to the Pediatric Oncology Therapeutic Experimental Investigators Consortium (POETIC), a collaborative clinical research group offering experimental therapies to patients with newly diagnosed, relapsed or refractory disease. It is also the New England Phase I Center of the Department of Defense Neurofibromatosis Clinical Trial Consortium

    Through these consortia, a number of novel therapies are available for children with both newly diagnosed and current brain tumors. Two new protocols include:

    • A Phase II trial of radiation therapy, cetuximab and irinotecan for children with newly diagnosed malignant glioma and diffuse intrinsic pontine glioma.
    • A second trial for newly diagnosed malignant gliomas is a Phase I gene immuno-therapy trial combined with radiation therapy and temozolomide. This combination stops the growth of malignant glioma cells and, more importantly, simulates an immune response that can eliminate malignant cells that have traveled beyond the tumor's primary site—a strategy that should help lower the risk of recurrence.

    Clinical trials

    For many children with brain tumors or other rare or hard-to-treat conditions, clinical trials provide new options. 

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