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Glioblastoma Multiforme

Glioblastoma Multiforme | American Association of Neurological Surgeons

A Neurosurgeon Explains: Glioblastoma Multiforme

Vikram C. Prabhu, MD, FAANS

Glioblastoma multiforme (GBM) (also called glioblastoma) is a fast-growing glioma that develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain.

GBM is often referred to as a grade IV astrocytoma. These are the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue.

GBMs can arise in the brain “de novo” or evolve from lower-grade astrocytomas or oligodendrogliomas. In adults, GBM occurs most often in the cerebral hemispheres, especially in the frontal and temporal lobes of the brain. GBM is a devastating brain cancer that typically results in death in the first 15 months after diagnosis.


GBMs are biologically aggressive tumors that present unique treatment challenges due to the following characteristics:

  • Localization of tumors in the brain
  • Inherent resistance to conventional therapy
  • Limited capacity of the brain to repair itself
  • Migration of malignant cells into adjacent brain tissue
  • The variably disrupted tumor blood supply which inhibits effective drug delivery
  • Tumor capillary leakage, resulting in an accumulation of fluid around the tumor; (peritumoral edema) and intracranial hypertension
  • A limited response to therapy
  • The resultant neurotoxicity of treatments directed at gliomas

Symptoms vary depending on the location of the brain tumor, but may include any of the following:

Sophisticated imaging techniques can very accurately pinpoint the location of brain tumors. Diagnostic tools include computed tomography (CT or CAT scan) and magnetic resonance imaging (MRI).

Intraoperative MRI may also be useful during surgery to guide tissue biopsies and tumor removal. Magnetic resonance spectroscopy (MRS) is used to examine the tumor's chemical profile, with positron emission tomography (PET scan) helpful in detecting tumor recurrence.

After a brain tumor is detected on a CT or MRI scan, a neurosurgeon obtains tumor tissue for a biopsy and the tissue is examined by a neuropathologist.

The analysis of tumor tissue under a microscope is used to assign the tumor a name, grade, and to provide answers to the following questions:

  • From what type of brain cell did the tumor arise? (The name of the tumor is derived from this; for example, astrocytomas arise from astrocytes.)
  • Are there signs of rapid growth in the tumor cells?
  • Are there any specific genetic mutations within the tumor that can help with prognosis and/or provide a target for therapy?

    The tumor name and grade help determine treatment options and also provide important information about prognosis. For more information on grading, click here.

    The mainstay of treatment for GBMs is surgery, followed by radiation and chemotherapy. The primary objective of surgery is to remove as much of the tumor as possible without injuring the surrounding normal brain tissue needed for normal neurological function (such as motor skills, the ability to speak and walk, etc.). However, GBMs are surrounded by a zone of migrating, infiltrating tumor cells that invade surrounding tissues, making it impossible to ever remove the tumor entirely. Surgery provides the ability to reduce the amount of solid tumor tissue within the brain, remove those cells in the center of the tumor that may be resistant to radiation and/or chemotherapy and reduce intracranial pressure. Surgery, by providing a debulking of the tumor, carries the ability to prolong the lives of some patients and to improve the quality of remaining life.

    In most cases, surgeons perform a craniotomy, opening the skull to reach the tumor site. This is done frequently with computer-assisted image-guidance and at times using intra-operative mapping techniques to determine the locations of the motor, sensory and speech/language cortex. Intraoperative mapping often involves operating on a patient while they are awake and mapping the anatomy of their language function during the operation. The doctor then decides which portions of the tumor are safe to resect.

    After surgery, when the wound is healed, radiation therapy can begin. The goal of radiation therapy is to selectively kill the remaining tumor cells that have infiltrated the surrounding normal brain tissue. In standard external beam radiation therapy, multiple sessions of standard-dose "fractions" of radiation are delivered to the tumor site as well as a margin in order to treat the zone of infiltrating tumor cells. Each treatment induces damage to both healthy and normal tissue.

    By the time the next treatment is given, most of the normal cells have repaired the damage, but the tumor tissue has not. This process is repeated for a total of 10 to 30 treatments, usually given once a day, five days a week; depending on the type of tumor. The use of radiation therapy provides most patients with improved outcomes and longer survival rates compared to surgery alone or the best supportive care.

    Radiosurgery is a treatment method that uses specialized radiation delivery systems to focus radiation at the site of the tumor while minimizing the radiation dose to the surrounding brain. Radiosurgery may be used in select cases for tumor recurrence, often using additional information derived from MRS or PET scans. It is rarely used in the initial treatment of GBM.

    Patients undergoing chemotherapy are administered special drugs designed to kill tumor cells. Chemotherapy with the drug temozolomide is the current standard of treatment for GBM. The drug is generally administered every day during radiation therapy and then for six to 12 cycles after radiation. Each cycle lasts for 28 days, with temozolomide given the first five days of each cycle, followed by 23 days of rest. While the aim of chemotherapy is long-term tumor control, it does so in only about 20 percent of patients. The decision to prescribe other forms of chemotherapy for tumor recurrence is based on a patient's overall health, type of tumor and extent of the cancer. Before considering chemotherapy, patients should discuss it with their oncologists and/or neuro-oncologists.

    Because surgery, radiation and chemotherapy are unlikely to result in a prolonged remission of GBM tumors, researchers are always investigating the use of innovative new treatments when the first line therapy has failed. These new treatments are done in clinical trials. A number of these treatments are available on an investigational basis at centers specializing in brain-tumor therapies. These include gene therapy, highly focused radiation therapy, immunotherapy and chemotherapies utilized in conjunction with vaccines. It is important to note that while some of these investigational treatments show promise, the most effective therapies introduced over the past three decades have improved median survival of GBM patients by an average of only three months.

    These websites offer additional helpful information on glioblastoma multiforme, its causes, as well as treatment options, support and more. (Note: these sites are not under the auspice of the American Association of Neurological Surgeons, and their listing here should not be seen as an endorsement of these sites or their content.)

    • American Brain Tumor Association
    • American Cancer Society
    • Brain Tumor Society
    • National Cancer Institute
    • The AANS does not endorse any treatments, procedures, products or physicians referenced in these patient fact sheets. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific neurosurgical advice or assistance should consult his or her neurosurgeon, or locate one in your area through the AANS’ Find a Board-certified Neurosurgeon” online tool.