It was a routine annual physical, and everything checked out fine. Blood pressure normal, electrocardiogram normal, weight good, no particular complaints--except one. The patient, 65-year-old Sylvia Zeidner of Potomac, Md., had been having some peculiar dizzy spells, and she laughingly told the doctor, "I must have a brain tumor."
She did. By taking her joking words seriously, the doctor saved her from more devastating symptoms and possibly saved her life. He sent her for an MRI, or magnetic resonance imaging, a noninvasive test approved by the Food and Drug Administration in the early 1980s that is especially valuable in diagnosing brain tumors. The MRI revealed a large baseball-sized tumor sitting on top of Zeidner's brainstem, in the lower back part of the skull.
Surgery was scheduled for a week later. The day before surgery, the radiologist threaded a catheter--a piece of flexible rubber tubing--from an incision in her groin up through her body to the brain and passed a substance through the catheter that blocked the tumor's blood supply, causing it to shrink. During the nine-hour-long operation the next day, the surgeon successfully removed from her brain a meningioma, a type of tumor (usually benign, not cancerous, as it was in this case) that grows from the meninges, the membrane covering the brain and spinal cord. Afterwards, when she inquired how so large a tumor could have caused so few symptoms, the doctor replied that the tumor had grown very slowly, perhaps over 20 years. The brain had gradually accommodated the tumor's increasing size until the pressure became too much and the brain cried out in protest. Since the brainstem controls vital functions, such as blood pressure, breathing and the beating of the heart, she could have died suddenly if the tumor had grown large enough to affect those vital systems.
In the United States, about 100,000 cases of brain tumors are predicted for 1996, almost double the number of just a decade ago. Of these, about 17,000 will originate from brain tissue and are called primary brain tumors. Secondary (metastatic) brain tumors, those seeded by cancer cells floating in the bloodstream from cancer of the breast, lung, kidney, skin, or other organs, will account for the remainder. (Cancer can spread from other parts of the body to the brain, but primary tumor cells rarely travel outside the brain.) The incidence of brain tumors, both primary and metastatic, appears to be increasing worldwide, especially among the elderly, and no one is sure why.
Only Some Causes Known
Brain tumors are abnormal growths of tissues within the skull. They can be benign, like Sylvia's, or can be malignant, meaning cancerous. Even benign brain tumors can be fatal when removal would damage vital brain centers, or if they are inaccessible because they lie buried deep inside the brain. Individuals of any age can develop brain tumors, but they occur more frequently in older adults and in children under the age of 15. (The only form of cancer that causes more childhood deaths is leukemia.) Certain brain tumors occur exclusively in children and adolescents, others in adults.
The causes of primary brain tumors are unknown. Researchers so far have not been successful in establishing a link between brain tumors and viruses, diet, injury, hormones, certain medications, smoking, alcohol, or other factors.
It is known that people who work with certain chemicals are at risk. Studies have shown that some types of brain tumors occur more frequently among workers in the oil refining, rubber manufacturing, and drug industries and among chemists and embalmers.
Many adults treated as children decades ago for scalp ringworm with high doses of ionizing radiation have developed brain tumors years after exposure.
People who have impaired immunity, such as those with AIDS or those who have undergone organ transplants, are also susceptible to brain tumors.
About 5 percent of primary brain tumors appear to be due to hereditary factors. Sometimes, several members of the same family have brain tumors. Certain rare inherited syndromes, such as neurofibromatosis, the "Elephant Man" disease, increase the risk of developing a brain tumor.
Many parents whose children have developed brain tumors--and who live near toxic waste sites or high-tension power lines--claim that exposure to these environmental hazards is responsible for the tumors. But since brain tumors occasionally occur in random "clusters," epidemiologists say that studies have not been able to prove a connection between such exposure and brain tumors.
Vague or Dramatic
Depending on the tumor's size, type and location, symptoms can be as vague as Sylvia's dizziness or as dramatic as the sudden seizure that shook the left side of the body of Lee Atwater, Republican party chairman, while he was addressing a GOP fund-raiser in 1990.
Eventually, all brain tumor symptoms get worse. Because the space inside the skull is limited, as the tumor grows it causes increased pressure on the brain. The tumor may also block the flow of cerebrospinal fluid, the watery cushion that protects the brain and spinal cord from shock. In young children, whose skulls have not yet fused, the head may enlarge in response to this pressure, causing a condition known as hydrocephalus.
Tumors in some locations produce characteristic symptoms. For example, tumors growing in the brain's occipital lobe, which interprets visual images, often cause lack of vision in part of the visual field of each eye. However, many common symptoms of brain tumors are similar to those of other diseases (see "Distinguishing Symptoms") and can result in misdiagnosis.
The neurological examination is one of the most helpful tools in the diagnosis of brain tumors. The neurologist checks eye movement, eye reflexes and pupil reaction, hearing, reflexes, sensation, movement, and balance and coordination.
Some laboratory tests, such as the electroencephalogram (EEG), are also useful in diagnosis. The EEG uses special patches placed on the scalp to record electrical currents. Certain patterns in the brain's electrical activity may suggest a local abnormality. Further investigation may turn up a tumor, stroke or other disorder.
For years, doctors diagnosed brain tumors with a technique called angiography. A series of x-ray images is made of the brain after a "dye" (a radiographic contrast material opaque to x-rays) is injected into a major blood vessel. The pictures make the brain's blood vessels visible.
If angiography is not much used today, it's because the diagnosis of brain tumors has been revolutionized in the last two decades by the development of special imaging techniques, such as computed tomography, or CAT scan. This test is especially useful in showing the tumor's location. A CAT scan is made by sending x-rays through the body at various angles and then assembling these images by computer to give cross-sectional views. This test is often used with contrast material injected into the patient. The dye helps outline certain parts of the brain and sometimes makes it easier for the doctor to see abnormal tissue, such as tumors.
Magnetic resonance imaging, or MRI, does not use x-rays, but rather subjects tissues to a strong, but harmless and painless, magnetic field. Unlike the CAT scan, which produces an image that depends on x-ray absorption, MRI produces an image that reflects magnetic properties of the body. One advantage of MRI is that the examination can be tailored to highlight different types of diseases. MRI used in conjunction with contrast materials containing magnetic substances (unlike those used in CAT scans) has been found to be very effective in imaging brain tumors.
Positron emission tomography (PET) is used less often than either CAT scanning or MRI because the equipment is more expensive. PET measures the brain's activity using positron-emitting radiopharmaceuticals, which are injected into the patient before the test. PET scans can be especially useful in detecting recurrent tumors.
To make a definitive diagnosis, doctors often take a small amount of tissue from a suspected tumor, which a pathologist examines under a microscope. This technique, called a biopsy, can reveal whether the cells are benign or malignant and can identify the type of tumor (there are many different types).
Standard treatments for brain tumors include surgery, radiation therapy, chemotherapy, or a combination of these approaches. Many benign tumors are treated by surgery alone, resulting in a complete cure. A highly malignant tumor, such as glioblastoma multiforme, also called high-grade astrocytoma, may require all three types of treatment.
The surgeon's aim is to remove the tumor completely without damaging normal brain tissue. To achieve this goal, a whole array of surgical tools has been developed in recent years.
Among the most important are exquisitely miniaturized devices such as the surgical microscope and microsurgical instruments, all regulated by FDA. Microsurgical techniques have made it possible for the neurosurgeon to remove tumors that were once considered inoperable.
"Surgical microscopes are continually being refined," says Steven Brem, M.D., Chief of Neurosurgery, at the H. Lee Moffitt Cancer Center, Tampa, Fla. "They're more flexible, more powerful, provide greater illumination, and are easier to use. They have definitely shortened surgical time." Magnification of the operating area has also made it easier for the surgeon to differentiate between tumor tissue and normal tissue.
Another tool used extensively by neurosurgeons is the ultrasonic aspirator, a device that uses high-frequency sound waves to break up tumors and an aspirator to "vacuum" tumor pieces. "The ultrasonic aspirator is a safe tool that has enabled the cure of benign tumors, especially those that are fibrous, or difficult to remove, or stuck to a nerve," says Brem.
Lasers release a beam of concentrated light energy that can destroy small areas of tumors and can help control bleeding. Those approved for use on brain tumors include carbon dioxide lasers and YAG lasers (Nd:YAG and frequency double Nd:YAG).
Radiation therapy is the use of high-energy beams of either x-rays or gamma rays to stop cancer cells from growing and multiplying. Radiation is used after surgery when the surgeon has not been able to remove every bit of cancerous tissue, or is used instead of surgery when a tumor is in a brain area where removal would harm the patient. Certain drugs called radiosensitizers--HU (hydroxyurea), BUdR (bromodeoxyuridine), and IUdR (5-iodo-2-deoxyuridine)--are sometimes given during radiation therapy. These drugs are still being tested. It is hoped that they will make tumor cells more sensitive to radiation therapy.
Another type of radiation treatment currently being used is interstitial brachytherapy. Radioactive "seeds" are planted directly into the brain tumor where they can remain for a period of time. This technique is useful for treating small tumors that cannot be removed surgically.
Radiation destroys cancer cells, but it can also damage adjacent healthy cells. To minimize this damage, doctors may use a special type of radiation treatment called stereotactic radiosurgery or radiotherapy to destroy tumors. One technique combines computer-based treatment planning and a therapy device called the Gamma Knife. Despite its name, this device is not a knife.
The patient is placed on a couch and is fitted with a curved steel helmet, much like a hair dryer, but with 201 small holes. The couch slides into a globe that beams 201 precisely focused gamma rays from radioactive cobalt through the holes to the targeted tumor. One session usually lasts from 15 to 45 minutes and can be repeated, if necessary.
The Gamma Knife is especially effective in shrinking or destroying small, well-circumscribed tumors (less than one and one-quarter inches in diameter) and tumors deep in the brainstem or in other inoperable sites. Radiosurgery can also be used after conventional radiation therapy to boost its effects. More than 41,000 people worldwide were treated with the gamma knife between 1968 and 1995.
Two other machines used in stereotactic radiosurgery--the cyclotron, used to accelerate particles, and a modified linear accelerator--also operate on the same principle as the gamma knife: the delivery of concentrated doses of radiation while sparing normal tissue.
Chemotherapy uses drugs to kill tumor cells. Drugs can be given by mouth, injected into a blood vessel or muscle, injected directly into the cerebrospinal fluid, or infused through a catheter to arteries supplying the brain with blood.
One stumbling block to the effectiveness of chemotherapy is the blood-brain barrier, an elaborate network of fine blood vessels and cells that keeps damaging substances in the blood from reaching the brain, but can keep out beneficial drugs as well.
"An important development in the treatment of malignant brain tumors has been the advent of intra-operative interstitial chemotherapy, which circumvents that old bugbear, the blood-brain barrier," says Brem. "This represents a new technology that I and many others in 45 major centers participated in. The study, completed in 1994, was a prospective, randomized, double-blind study [no one knew who received the placebo, or who received the drug] in which biodegradable slow-release polymers [Gliadel wafers] were implanted into the tumor bed after surgery. The surgeon can remove all the gross disease, but 90 percent [of tumors] recur within 2 centimeters. These slow-release wafers, which are impregnated with chemotherapy--BCNU [carmustine]--have been shown to prolong survival." Gliadel wafers are now approved for use in patients who undergo surgery for recurrence of glioblastoma multiforme.
Doctors can treat patients who have certain types of malignant primary brain tumors (and some benign tumors that progress despite surgery and radiation) with chemotherapy before, during or after surgery or radiation. Chemotherapy has been successful in young children and is preferred in many cases to radiation, which can injure developing brains.
The doctor must maintain a delicate balance between giving enough chemotherapy to kill cancer cells, but not so much as to destroy healthy cells. Drugs can be used alone, but are also used in combinations, which are often more effective against the tumor. Other medications that do not affect the tumor but relieve symptoms are corticosteroids to reduce brain swelling and anticonvulsants to prevent seizures.
Cancerous tumor cells, which divide rapidly, can be killed by chemotherapy, but some normal rapidly dividing cells, such as blood, hair follicles, skin, and the cells lining the digestive tract, can also be affected. That's why chemotherapy sometimes causes hair loss and other side effects, such as nausea and vomiting, loss of appetite, diarrhea, anemia, mouth sores, and lowered resistance to infection.
Early Diagnosis Makes a Difference
About half of all primary brain tumors are relatively benign tumors that can be successfully treated, according to the American Brain Tumor Association. Many malignant tumors, including malignant primary brain tumors, such as medulloblastoma in children, are curable by surgery, radiation therapy, and chemotherapy. The most important predictors of a successful outcome are early diagnosis--based on the physician's awareness of common symptoms, as in Sylvia Zeidner's case--and proper management of the disease by a multidisciplinary team of doctors skilled in all phases of diagnosis and treatment.
Zeidner has been having mild headaches since her surgery a year ago, but a recent MRI did not show any recurrence of her meningioma. The neurosurgeon explained that the tumor's removal had left a large cavity in her brain, which has been filling with more fluid than the brain could absorb, thus causing the headaches.
If the headaches get worse, the excess fluid could be drained by a shunt, a tube that is inserted into the head and then threaded under the skin to another body cavity, most commonly the abdomen, where the fluid drains and is absorbed.
Though implanting a shunt is a relatively minor procedure, Zeidner feels she is not that much bothered by her headaches and has opted to treat them with over-the-counter painkillers, which are effective, rather than undergo another round of surgery.
Brain tumor symptoms may resemble symptoms of so many other disorders, including stroke and less life-threatening diseases, that it may be difficult for the doctor to make a diagnosis. For example, headaches--the most common symptom--may be caused by sinus infections or migraine, nausea may be due to gallbladder disease, and dizziness may be a symptom of Menière's disease.
A CAT scan or MRI can help establish the presence of a brain tumor that may be responsible for any of these symptoms:
- Headaches. Meriting a visit to the doctor include headaches that are: worse in the morning and then improve during the day; persistent and accompanied by nausea and vomiting, especially sudden vomiting; and accompanied by double vision, weakness or numbness.
- seizures (convulsions), especially in an adult
- gradual loss of movement or feeling in an arm or leg
- stumbling, unsteadiness or imbalance
- vision or hearing loss
- speech difficulty
- personality changes
- drowsiness or confusion
- loss of memory or concentration.
More information on brain tumors is available from:
National Cancer Institute
Office of Cancer Communications
Room 10A-24, Building 31
Bethesda, MD 20892
(1-800) 4-CANCER [(1-800) 422-6237]
TTY: (1-800) 332-8615
World Wide Web: http://www.nci.nih.gov/
(information on nonmalignant tumors)
National Institute of Neurological Disorders and Stroke
Room 8A-06, Building 31
31 Center Drive
Bethesda, MD 20892-2540
World Wide Web: http://www.ninds.nih.gov/
FDA / FDA Consumer