Updated June 2012
Glioblastoma multiforme (GBM) (also called glioblastoma) is a fast-growing glioma that develops from astrocytes — star-shaped glial cells that support nerve cells. GBM is classified as a grade IV astrocytoma. These are the most invasive type of glial tumors, rapidly growing and commonly spreading to nearby brain tissue. They may be composed of several different kinds of cells (i.e. astrocytes, oligodendrocytes). Sometimes, they evolve from a low-grade astrocytoma or an oligodendroglioma. 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 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 neurotoxicity of treatments directed at gliomas
Prevalence and Incidence
The National Cancer Institute estimates that 22,910 adults (12,630 men and 10,280 women) will be diagnosed with brain and other nervous system tumors in 2012. It also estimates that in 2012, 13,700 of these diagnoses will result in death.
GBM accounts for about 15 percent of all brain tumors and primarily occurs in adults between the ages of 45 and 70. Between 2005 and 2009, the median age for death from cancer of the brain and other areas of the nervous system was age 64.
Symptoms vary depending on the location of the brain tumor, but may include any of the following:
Sophisticated imaging techniques can pinpoint brain tumors. Diagnostic tools include computed tomography (CT or CAT scan) and magnetic resonance imaging (MRI). Intraoperative MRI also is used during surgery to guide tissue biopsies and tumor removal. Magnetic resonance spectroscopy (MRS) is used to examine the tumor's chemical profile and determine the nature of the lesions seen on the MRI. Positron emission tomography (PET scan) can help detect recurring brain tumors.
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 name and grade, and provides answers to the following questions: 1) 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.); 2) Are there signs of rapid growth in the tumor cells?
The tumor name and grade help determine treatment options and also provide important information about prognosis. For more information on grading, click here.
Palliative care, without any active intervention or treatment, is an option for patients who are disabled. Treatment options for others include surgery, radiation, radiosurgery or chemotherapy. The primary objective of surgery is to remove as much of the tumor as possible without injuring brain tissue needed for neurological function (such as motor skills, the ability to speak and walk, etc.). However, high-grade tumors are surrounded by a zone of migrating, infiltrating tumor cells that invade surrounding tissues, making it more difficult to remove the entire tumor. If the tumor cannot be removed completely, surgery can reduce the amount of solid tumor tissue, remove those cells in the center of the tumor that may be resistant to treatment and reduce intracranial pressure. Debulking surgery can prolong the lives of some patients or 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 image guidance, and at times using intra-operative mapping techniques to determine the locations of motor, sensory and speech/language cortex. Intraoperative mapping involves operating on a conscious patient and mapping the anatomy of their language function during the operation. The doctor then decides which portions of the tumor are safe to resect.
Sometime after surgery, when the wound is healed, radiation therapy can begin. The goal of radiation therapy is to kill tumor cells selectively while leaving normal brain tissue unharmed. 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, depending on the type of tumor. This additional treatment 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 (magnetic resonance spectroscopy) or PET scans (positron emission tomography).
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 administered every day during radiation therapy and then in six to eight cycles for five days at higher doses once radiation is completed. 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 traditional methods of treatment are unlikely to result in a prolonged remission of GBM tumors, researchers presently are investigating several innovative treatments 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. One promising vaccine and chemotherapy study yielded an average time for recurrence of the tumor after treatment of 16.6 months, as compared to the previous six-month average recurrence. However, 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.
Glioblastoma Multiforme Resources
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 AANS, and their listing here should not be seen as an endorsement of these sites or their content).
American Brain Tumor Association – www.abta.org
American Cancer Society – www.cancer.org
Brain Tumor Society – www.braintumor.org
National Cancer Institute – www.cancer.gov/cancertopics/types/brain/