Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. These tumors are often aggressive and infiltrate surrounding brain tissue. GBMs arise from glial cells, which are cells that form the tissue that surrounds and protects other nerve cells found within the brain and spinal cord. GBMs are mainly composed of star-shaped glial cells known as astrocytes. The general term glioma includes any type of brain tumor such as astrocytoma and oligodendroglioma that arise from glial cells.
Astrocytomas are classified according to a grading system developed by the World Health Organization (WHO). Astrocytomas come in four grades based upon how fast the cells are reproducing and that likelihood that they will infiltrate nearby tissue. Grades I or II astrocytomas are nonmalignant and may be referred to as low-grade. Grades III and IV astrocytomas are malignant and may be referred to as high-grade astrocytomas. Grade III astrocytomas are known as anaplastic astrocytomas. Grade IV astrocytomas are known as glioblastoma multiforme.
The symptoms of glioblastoma multiforme vary depending upon the exact location and size of the tumor. Most symptoms result from increased pressure within the brain.
Increased pressure within the brain may be caused by the tumor itself or by blockage of the fluid-filled spaces in the brain called ventricles, which results in the abnormal accumulation of cerebrospinal fluid (CSF) in the brain. Symptoms associated with increased pressure within the brain include headaches, lethargy or drowsiness, nausea, vomiting, and changes in personality or mental status. In some cases, seizures, vision problems, loss of previously acquired speech and language skills (aphasia), and weakness of the arms and legs resulting in coordination difficulties may also occur.
GBMs may grow rapidly and infiltrate nearby normal brain tissue, eventually causing life-threatening complications. GBMs usually do not spread outside of the central nervous system, although it can happen in extremely rare cases.
The exact underlying cause of glioblastoma multiforme is unknown. Some cases may develop from existing, low-grade astrocytomas (malignant transformation) or they may occur without any evidence of a previous tumor (de novo).
Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., exposure to ultraviolet rays, certain chemicals, ionizing radiation), diet, stress, and/or other factors may play contributing roles in causing specific types of cancer. However, no conclusive evidence has thus far demonstrated a direct causal relationship between these factors and the induction of GBM tumors in human patients. GBMs arise spontaneously in 95% of patients. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer.
In individuals with cancer, including GBM, malignancies may develop due to abnormal changes in the structure and orientation of cells secondary to oncogenes or the loss of tumor suppressor genes. Oncogenes control cell growth; tumor suppressor genes control cell division and ensure that cells die at the proper time. The specific cause of changes to these genes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body’s genetic code, are the underlying basis of cellular malignant transformation. These abnormal genetic changes may occur spontaneously for unknown reasons or, more rarely, may be inherited.
In cells that have undergone malignant transformation, there is typically reversion to a less specialized, more primitive form (anaplasia or loss of “differentiation”), meaning that they are no longer capable of performing their “intended,” specialized functions within the tissue in question. Malignant cells pass their abnormal changes on to all their “daughter” cells and typically grow and divide at an unusually rapid, uncontrolled rate that cannot be contained by the body’s natural immune defenses. Eventually, such proliferation of abnormal cells may result in formation of a mass known as a tumor (neoplasm). The genetic abnormalities may change over time and within different cells within the tumor making the tumor heterogenous (i.e. the cells within the tumor are not identical).
Researchers have identified several different genes that may play a role in the development or progression of GBM. Individuals with different genetic mutations may respond differently to therapies and certain mutations may be associated with different disease progression or response to therapy. Further study into the molecular changes in GBM will be helpful in improving the diagnosis and treatment of this cancer.
Glioblastoma multiforme affects males slightly more often than females and adults more often than children. Most cases develop in individuals between 40 and 60 years of age. GBM is the most common primary brain tumor accounting for approximately 50 percent of cases of primary brain tumors (i.e. excluding diseases that metastasize to the brain from other sites in the body). GBM accounts for approximately 3-4 percent of primary childhood brain tumors. The incidence is estimated to be 2-3 people per every 100,000 in the United States and most European countries.
A diagnosis of glioblastoma multiforme is made based upon a thorough clinical evaluation, a detailed patient history, and a variety of imaging techniques including computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. Such imaging techniques may also be used to evaluate the size and extension of the tumor and to serve as an aid for future surgical procedures.
Surgical removal or a biopsy from the tumor and the resulting microscopic evaluation may confirm a diagnosis. The grading of astrocytoma tumors can sometimes be difficult with limited sampling (biopsy). Because the tumor is heterogeneous, one area of the tumor may look like an anaplastic astrocytoma but another area like GBM. The highest grade defines how the tumor is typically treated by the oncologist.
The therapeutic management of individuals with a GBM may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists or neuro-oncologists), specialists in the use of radiation to treat cancer (radiation oncologists), neurosurgeons, oncology nurses, and other specialists.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as primary tumor location; extent of the tumor infiltration into the surrounding normal brain tissues; the degree of malignancy (grade); an individual's age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of the case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.
The three main forms of treatment for GBM are surgery, radiation and chemotherapy. These treatments may be used alone but usually in combination with one another. The initial treatment in most cases is surgical excision to remove as much as the tumor as possible (resection). Often, only a portion of the tumor can be safely removed because malignant cells may have infiltrated brain in functionally crucial areas. Surgery cannot remove every cell of the tumor, thus radiation therapy and chemotherapy are used following surgery to continue treatment.
Postoperative radiation is used to treat residual disease in GBM patients. If initial surgery is not an option due to the specific location of the tumor, therapy may include radiation alone. Radiation therapy preferentially destroys or injures rapidly dividing cells, primarily cancerous cells. However, some healthy cells (e.g., hair follicles, bone marrow, etc.) may also be damaged, leading to certain side effects. Thus, during such therapy, the radiation is passed through diseased tissue in carefully calculated dosages to destroy cancer cells while minimizing exposure and damage to normal cells. Radiation therapy works to destroy cancer cells by depositing energy that damages their genetic material, preventing or slowing their growth and replication.
Therapy with anticancer drugs (chemotherapy) is commonly used to treat individuals with GBM often following surgery. Most chemotherapeutic agents have demonstrated only limited effectiveness for treating individuals with GBM. However, the Food and Drug Administration (FDA) has approved temozolomide (Temodar) for the treatment of adults with GBM. Temozolomide is typically used concurrently with radiation therapy and then is frequently continued for 6 months to 1 year thereafter. For more information, contact:
2000 Galloping Hill Road
Kenilworth, N.J. 07033-0530
Another drug product known as Gliadel wafers has been approved by the FDA for the treatment of individuals with GBM as an adjunct to surgery and radiation. These biodegradable wafers contain the chemotherapy carmustine (BCNU). Several of the wafers are placed in the cavity created during the surgical removal of a GBM. The wafers release the drugs into the surrounding tissue over a period of two or three weeks. For more information, contact:
MGI Pharma, Inc.
5775 West Old Shakopee Road
Bloomington, M. 55437
Phone: (952) 346-4700
Fax: (352) 346-4800
On May 8th, 2009 the U.S. Food and Drug Administration recently approved Avastin (bevacizumab) to treat patients with glioblastoma multiforme (GBM) when this form of brain cancer continues to progress following standard therapy.
Avastin is a laboratory-produced molecule known as a monoclonal antibody that mimics the antibodies produced by the body's immune system to defend against harmful substances. The medication inhibits the action of vascular endothelial growth factor that helps form new blood vessels. These vessels can feed a tumor, helping it to grow and can also provide a pathway for cancer cells to circulate in the body.
The drug was first approved in 2004 to treat metastatic cancer of the colon or rectum and has since been approved for treatment of non-squamous, non-small cell lung cancer and metastatic breast cancer.
Avastin is manufactured by Genentech Inc. of San Francisco.
Additional medications may be used to treat GBM including pain medications, steroids to reduce swelling in the brain, and anti-seizure (anti-convulsant) medications
Researchers are studying new ways to treat individuals with GBM including different radiation therapy techniques; new chemotherapy drugs; new combinations of chemotherapy drugs; drugs that stop blood vessel formation (angiogenesis) thereby cutting off blood flow to the tumor; immunotherapy, in which the body’s own defenses are stimulated and directed against tumor tissue; molecular therapy, and gene therapy.
Currently (2007) there are approximately 200 clinical trials listed with the National Institutes of Health that are investigating treatments for patients with gliomas. Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact
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