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  • Reviewed: 12/13/2010
CANCER ADVANCES IN FOCUS: Brain and Other Central Nervous System
Yesterday

  • In 1975, the annual incidence of brain and other central nervous system (CNS) cancers, including cancers of the spinal cord, among adults in the United States was 5.9 new cases diagnosed for every 100,000 persons. The incidence of these cancers among children aged 19 years or younger was 2.1 new cases per 100,000 persons.

  • In the same year, the annual mortality from brain and other CNS cancers among adults was 4.1 deaths per 100,000 persons; among children aged 19 years or younger, it was 0.9 deaths per 100,000 persons.

  • Magnetic resonance imaging (MRI), which facilitates diagnosis as well as treatment of brain and other CNS tumors with surgery and radiation therapy, first became widely available in the 1980s.

  • Clinical trials in the 1970s and 1980s showed that adding radiation therapy to surgery prolonged the survival of patients with glioma, a type of brain tumor that accounts for approximately 70% of the malignant primary brain tumors diagnosed in adults in the United States each year.

  • Chemotherapy was not a standard treatment for brain tumors because most early chemotherapy drugs could not cross the blood-brain barrier. One class of drugs, the nitrosoureas, was found to cross the blood-brain barrier and was shown in clinical trials to produce a small but clear improvement in the length of patient survival when combined with surgery and radiation therapy.

Today

  • In 2007, the latest year for which we have updated statistics, the U.S. incidence rate of brain and other CNS cancers among adults was 6.4 new cases per 100,000 persons; among children aged 19 years or younger, it was 2.9 new cases per 100,000 persons. The higher incidence rates observed today are likely due, in part, to an improved ability to diagnose brain and other CNS tumors with advanced imaging technologies.

  • MRI is now an accepted standard technology for imaging brain and other CNS tumors. A newer technology called functional MRI, which measures changes in blood flow that accompany brain activity, can be helpful in determining how well brain regions are working, in assessing potential risk from surgery, and in planning treatment. New intraoperative MRI machines can be used to monitor the extent of tumor removal during surgery.

  • The orally administered drug temozolomide, which first became available in the United States in 1999, can prolong the survival of patients with glioma when combined with radiation therapy. High-dose chemotherapy regimens for the treatment of some types of childhood brain tumor can delay the need for radiation therapy, possibly reducing harm to the developing brain.

  • Antiangiogenesis agents—drugs that block the growth of new blood vessels to tumors—have shown some promise in the treatment of gliomas. Gliomas are highly vascularized tumors, meaning they have a large number of blood vessels. Drugs that block the development of these blood vessels are being tested in clinical trials of patients with brain tumors. Based on the promising results of two clinical trials, one of which was conducted at the National Institutes of Health (NIH), the Food and Drug Administration gave accelerated approval in May 2009 to the antiangiogenesis agent bevacizumab (Avastin®) for the treatment of recurrent glioblastoma, which is the most common form of glioma. Two phase III clinical trials, including one supported by NIH, are testing the drug in newly diagnosed patients.

  • Advanced radiation therapy techniques that target tumor tissue more precisely and reduce radiation damage to surrounding normal tissue (such as 3-dimensional conformal therapy, stereotactic radiation therapy, and intensity-modulated radiation therapy) are being refined.

  • Researchers are exploring the use of other novel approaches, such as targeted therapy, gene therapy, immunotherapy, and vaccine therapy, for the treatment of brain and other CNS cancers.

  • A new scale developed by NIH, which is based on tumor size, tumor location, and a patient’s ability to perform everyday tasks, can help surgeons identify which patients with glioblastoma will benefit from additional surgery when their tumor recurs.

  • Scientists are beginning to understand the genetic complexity of brain tumors, which will facilitate the design of more effective treatments. An understanding of the genetic changes that drive the growth of brain tumors will allow researchers to choose the best candidate targeted drugs for testing in clinical trials.

  • In 2008, The Cancer Genome Atlas (TCGA) project reported the first results of its large-scale, comprehensive study of gene changes in glioblastoma (a type of glioma). These results identified three previously unrecognized mutations that occur frequently in glioblastoma and three cell-signaling pathways that may help drive tumor growth. The results also shed new light on molecular mechanisms that may make tumors resistant to some chemotherapy drugs. In 2010, additional results from TCGA showed that glioblastoma comprises four different molecular subtypes that have different responses to chemotherapy and radiation therapy.

  • The Glioma Molecular Diagnostic Initiative has already made extensive genetic and related clinical data from more than 800 glioma patients available to researchers worldwide in a public data repository and bioinformatics work space known as REMBRANDT.

  • Despite tremendous advances in our understanding of brain cancer biology, substantial progress in brain tumor diagnosis and treatment, and marked improvements in the quality of life of brain tumor patients, the mortality rate for brain and other CNS cancers has remained largely unchanged over the past 30 to 40 years.

Tomorrow

  • We will continue to explore the use of new imaging technologies in the diagnosis, treatment, and follow-up care of brain and other CNS cancers. For example, magnetic resonance perfusion imaging is a technology that enables measurement of the volume of blood flowing through the brain. This information will allow better estimates of tumor grade, size, and location before surgery and permit recurrent tumor tissue to be distinguished from damage to brain tissue caused by radiation therapy, thereby reducing the need for follow-up surgical biopsies. In addition, imaging technologies such as positron emission tomography, single photon emission computed tomography, and diffusion-weighted MRI can help measure tumor metabolic activity, tumor cell proliferation, and the amount of oxygen that reaches tumor cells.

  • We will refine methods of delivering chemotherapy drugs and other agents to the brain and CNS, including the development of drugs that have the ability to penetrate the blood-brain barrier. Other delivery techniques, such as convection-enhanced delivery, in which drugs or other anticancer agents are delivered under pressure (convection) through a catheter inserted directly into or near a tumor, may prove valuable.

  • We will continue to explore the potential of new antiangiogenesis agents in controlling tumor growth.

  • Intensive research into the genetic changes that lead to the formation of brain and other CNS cancers, through TCGA and other collaborative projects, will yield new opportunities for developing therapies that target these changes.

  • We will expand our understanding of the role that tumor stem cells play in the formation of brain and other CNS tumors and their resistance to treatment and will use that knowledge to develop new therapies that target tumor stem cell-signaling pathways. First discovered in 2003, brain tumor stem cells make up only a small proportion of the cells in human brain tumors, but they may drive tumor growth and metastasis and contribute to resistance to treatment.

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Glossary Terms

3-dimensional conformal radiation therapy (3-dih-MEN-shuh-nul kun-FOR-mul RAY-dee-AY-shun THAYR-uh-pee)
A procedure that uses a computer to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. Also called 3-dimensional radiation therapy and 3D-CRT.
antiangiogenesis (AN-tee-AN-jee-oh-JEH-neh-sis)
Prevention of the growth of new blood vessels.
bevacizumab (beh-vuh-SIH-zoo-mab)
A drug used to treat glioblastoma (a type of brain cancer) and certain types of colorectal cancer, lung cancer, and kidney cancer. It is also being studied in the treatment of other types of cancer. Bevacizumab binds to a protein called vascular endothelial growth factor (VEGF). This may prevent the growth of new blood vessels that tumors need to grow. It is a type of antiangiogenesis agent and a type of monoclonal antibody. Also called Avastin.
bioinformatics (BY-oh-in-for-MA-tix)
The science of using computers, databases, and math to organize and analyze large amounts of biological, medical, and health information. Information may come from many sources, including patient statistics, tissue specimens, genetics research, and clinical trials.
blood-brain barrier (blud-brayn BAYR-ee-er)
A network of blood vessels and tissue that is made up of closely spaced cells and helps keep harmful substances from reaching the brain. The blood-brain barrier lets some substances, such as water, oxygen, carbon dioxide, and general anesthetics, pass into the brain. It also keeps out bacteria and other substances, such as many anticancer drugs. Also called BBB.
brain tumor (brayn TOO-mer)
The growth of abnormal cells in the tissues of the brain. Brain tumors can be benign (not cancer) or malignant (cancer).
central nervous system (SEN-trul NER-vus SIS-tem)
The brain and spinal cord. Also called CNS.
chemotherapy (KEE-moh-THAYR-uh-pee)
Treatment with drugs that kill cancer cells.
clinical trial (KLIH-nih-kul TRY-ul)
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.
computed tomography scan (kum-PYOO-ted toh-MAH-gruh-fee skan)
A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computerized axial tomography scan, computerized tomography, and CT scan.
gene therapy (jeen THAYR-uh-pee)
A type of experimental treatment in which foreign genetic material (DNA or RNA) is inserted into a person's cells to prevent or fight disease. Gene therapy is being studied in the treatment of certain types of cancer.
glioblastoma (GLEE-oh-blas-TOH-muh)
A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more often than the spinal cord. Also called GBM, glioblastoma multiforme, and grade IV astrocytoma.
glioma (glee-OH-muh)
A cancer of the brain that begins in glial cells (cells that surround and support nerve cells).
immunotherapy (IH-myoo-noh-THAYR-uh-pee)
Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in immunotherapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biological therapy, biotherapy, and BRM therapy.
incidence (IN-sih-dents)
The number of new cases of a disease diagnosed each year.
intensity-modulated radiation therapy (in-TEN-sih-tee-MAH-juh-LAY-tid RAY-dee-AY-shun THAYR-uh-pee)
A type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Also called IMRT.
magnetic resonance imaging (mag-NEH-tik REH-zuh-nunts IH-muh-jing)
A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. Magnetic resonance imaging makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. Magnetic resonance imaging is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called MRI, NMRI, and nuclear magnetic resonance imaging.
magnetic resonance perfusion imaging (mag-NEH-tik REH-zuh-nunts per-FYOO-zhun IH-muh-jing)
A special type of magnetic resonance imaging (MRI) that uses an injected dye in order to see blood flow through tissues. Also called perfusion magnetic resonance imaging.
mortality (mor-TA-lih-tee)
The state of being mortal (destined to die). Mortality also refers to the death rate, or the number of deaths in a certain group of people in a certain period of time. Mortality may be reported for people who have a certain disease, live in one area of the country, or who are of a certain gender, age, or ethnic group.
nitrosourea (ny-TROH-soh-YOO-ree-uh)
An anticancer drug that can cross the blood-brain barrier. Carmustine and lomustine are nitrosoureas.
positron emission tomography scan (PAH-zih-tron ee-MIH-shun toh-MAH-gruh-fee skan)
A procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is used. Because cancer cells often use more glucose than normal cells, the pictures can be used to find cancer cells in the body. Also called PET scan.
radiation therapy (RAY-dee-AY-shun THAYR-uh-pee)
The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.
recurrent cancer (ree-KER-ent KAN-ser)
Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrence.
spinal cord (SPY-nul kord)
A column of nerve tissue that runs from the base of the skull down the back. It is surrounded by three protective membranes, and is enclosed within the vertebrae (back bones). The spinal cord and the brain make up the central nervous system, and spinal cord nerves carry most messages between the brain and the rest of the body.
stem cell (stem sel)
A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.
stereotactic radiation therapy (STAYR-ee-oh-TAK-tik RAY-dee-AY-shun THAYR-uh-pee)
A type of external radiation therapy that uses special equipment to position the patient and precisely deliver radiation to a tumor. The total dose of radiation is divided into several smaller doses given over several days. Stereotactic radiation therapy is used to treat brain tumors and other brain disorders. It is also being studied in the treatment of other types of cancer, such as lung cancer. Also called stereotactic external-beam radiation therapy and stereotaxic radiation therapy.
surgery (SER-juh-ree)
A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.
targeted therapy (TAR-geh-ted THAYR-uh-pee)
A type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells. Targeted therapy may have fewer side effects than other types of cancer treatments.
temozolomide (teh-moh-ZOH-loh-mide)
A drug that is used to treat certain types of brain tumors in adults and is being studied in the treatment of other types of cancer. It belongs to the family of drugs called alkylating agents. Also called Temodar.
vaccine therapy (vak-SEEN THAYR-uh-pee)
A type of treatment that uses a substance or group of substances to stimulate the immune system to destroy a tumor or infectious microorganisms such as bacteria or viruses.

Table of Links

1http://www.cancer.gov/cancertopics/cancer-advances-in-focus