Brain and Spinal Cord Tumors — Hope Through Research

Brain and Spinal Cord Tumors, Hope Through Research
Source: National Cancer Institute

Introduction

The diagnosis of a brain or spinal cord tumor often comes as a shock, leaving confusion, uncertainty, fear, or even anger in its wake. After the diagnosis, a physician’s explanation can fall on ears deafened by this blow. Although it cannot substitute for the advice and expertise of a physician, this brochure is designed to convey the latest research information on the diagnosis, course, and possible treatment of various brain and spinal cord tumors, so that patients and their families have the information they need to become active participants in their treatment.

What are Brain and Spinal Cord Tumors?

Brain and spinal cord tumors are abnormal growths of tissue found inside the skull or the bony spinal column. The word tumor is used to describe both abnormal growths that are new (neoplasms) and those present at birth (congenital tumors). This brochure will focus primarily on neoplasms.

No matter where they are located in the body, tumors are usually classed as benign (or non-cancerous) if the cells that make up the growth are similar to other normal cells, grow relatively slowly, and are confined to one location. Tumors are called malignant (or cancerous) when the cells are very different from normal cells, grow relatively quickly, and can spread easily to other locations.

In most parts of the body, benign tumors are not particularly harmful. This is not necessarily true in the brain and spinal cord, which are the primary components of the central nervous system (CNS). Because the CNS is housed within rigid, bony quarters (that is, the skull and spinal column), any abnormal growth can place pressure on sensitive tissues and impair function. Also, any tumor located near vital brain structures or sensitive spinal cord nerves can seriously threaten health. If a benign tumor is found deep inside the brain, surgery to remove it may be very risky because of the chances of damaging vital brain centers. On the other hand, a benign tumor located near the brain’s surface can often be removed surgically.

An important difference between malignant tumors in the CNS and those elsewhere in the body lies with their potential to spread. While malignant cells elsewhere in the body can easily seed tumors inside the brain and spinal cord, malignant CNS tumors rarely spread out to other body parts. Laboratory and clinical investigators are exploring the basis of these unusual characteristics of CNS tumors, because these unique properties may suggest new strategies to prevent or treat them.

What Causes These Tumors?

When newly formed tumors begin within the brain or spinal cord, they are called primary tumors. Primary CNS tumors rarely grow from neurons, nerve cells that perform the nervous system’s important functions, because once neurons are mature they no longer divide and multiply. Instead, most tumors are caused by out-of-control growth among cells that surround and support neurons. Primary CNS tumors, such as gliomas and meningiomas, are named by the types of cells comprising them, their location, or both. The appendix at the end of this brochure describes many types of primary CNS tumors, as well as other tumor-related conditions.

In a small number of individuals, primary tumors may result from specific genetic diseases, such as neurofibromatosis and tuberous sclerosis, or exposure to radiation or cancer-causing chemicals. Although smoking, alcohol consumption, and certain dietary habits are associated with some types of cancers, they have not been linked to primary brain and spinal cord tumors.

In fact, the cause of most primary brain and spinal cord tumors, and most cancers, remains a mystery. Scientists do not know exactly why and how cells in the nervous system or elsewhere in the body lose their normal identity as nerve, blood, skin, or other cell types and grow uncontrollably. Research scientists are looking for clues to this process with the goals of learning why and how cancer begins and developing new tools to stop it. Some of the possible causes under investigation include viruses, defective genes, and chemicals.

Metastatic tumors are caused by cancerous cells that shed from tumors in other parts of the body, travel through the bloodstream, burrow through the blood vessel walls, latch onto tissue, and spawn new tumors inside the brain or spinal cord.

For every four people who have cancer that has spread within the body, one develops metastasis within the CNS. The top two culprits that lead to these secondary CNS tumors are lung and breast cancer. Other, less frequent causes of CNS metastases include kidney (renal) cancer, lymphoma (a cancer affecting immune cells), prostate cancer, and melanoma, a form of skin cancer.

Brain and spinal cord tumors are not contagious or, at this time, preventable.

How Many People Have These Tumors?

Research studies suggest that new brain tumors arise in more than 40,000 Americans each year. About half of these tumors are primary, and the remainder are metastatic.

Individuals of any age can develop a brain tumor. In fact, they are the second most common cause of cancer-related death in people up to the age of 35, with a slight peak in occurrence among children between the ages of 6 and 9. However, brain tumors are most common among middle-aged and older adults. People in their 60s face the highest risk, each year 1 of every 5,000 people in this age group develops a brain tumor.

Spinal cord tumors are less common than brain tumors. About 10,000 Americans develop primary or metastatic spinal cord tumors each year. Although spinal cord tumors affect people of all ages, they are most common in young and middle-aged adults.

By studying the epidemiology of CNS tumors, scientists can learn if different tumors are more common at certain ages or in certain people. This information, in turn, may reveal environmental factors that are linked to tumors, connections between tumors and other disorders, or patterns of tumor occurrence, all of which offer clues about why tumors develop.

What Are the Symptoms?

Brain and spinal cord tumors cause many diverse symptoms, which can make detection tricky. Whatever specific symptoms a patient has, the symptoms generally develop slowly and worsen over time.

A 3.5-pound wrinkled mass of tissue, the brain orchestrates behavior, movement, feeling, and sensation. It controls automatic functions like breathing and heartbeat. Many of these important functions are controlled by specialized brain areas. For example, the brain’s left and right hemispheres jointly control hearing and vision; the front part of each hemisphere controls voluntary movements, like writing, for the opposite side of the body; and the brain stem is responsible for basic life-sustaining functions, including blood pressure, heartbeat, and breathing.

As a result, brain tumors can cause a bewildering array of symptoms depending on their size, type, and location. Certain symptoms are quite specific because they result from damage to particular brain areas. Other, more general symptoms are triggered by increased pressure within the skull as the growing tumor encroaches on the brain’s limited space or blocks the flow of cerebrospinal fluid (fluid that bathes the brain and spinal cord). Some of the more common symptoms of a brain tumor include:

Headaches. More than half of people with brain tumors experience headaches. Because the skull cannot expand, the growing mass places pressure on pain-sensitive areas. The headaches recur, often at irregular periods, and can last several minutes or hours. They may worsen when coughing, changing posture, or straining. As the tumor grows, headaches often last longer, become more frequent, and grow more severe.
Seizures. The abnormal tissue found in a brain tumor can disrupt the normal flow of electricity through which brain cells communicate. The resulting bursts of electrical activity cause seizures with a variety of symptoms, such as convulsions, loss of consciousness, or loss of bladder control. Seizures that first start in adulthood (in a patient who has not been in an accident or had an illness that causes seizures) are a key warning sign of brain tumors. Sometimes, seizures are the only sign of a slowly growing brain tumor.
Nausea and vomiting. Increased pressure within the skull can cause nausea and vomiting. These symptoms sometimes accompany headaches.
Vision or hearing problems. Increased intracranial pressure can also decrease blood flow in the eye and trigger swelling of the optic nerve, which in turn causes blurred vision, double vision, or partial visual loss. Tumors growing on or near sensory nerves often trigger visual or hearing disturbances, such as ringing or buzzing sounds, abnormal eye movements or crossed eyes, and partial or total loss of vision or hearing. Tumors that grow in the brain’s occipital lobe, which interprets visual images, may also cause partial vision loss.
Behavioral and cognitive symptoms. Because they strike at the core of the individual’s identity, changes in behavior and personality can be the most frightening and devastating symptoms of a brain tumor. These symptoms usually occur when the tumor is located in the brain’s cerebral hemispheres, which are responsible, in part, for personality, communication, thinking, behavior, and other vital functions. Examples include problems with speech, language, thinking, and memory, or psychotic episodes and changes in personality.
Motor problems. When tumors affect brain areas responsible for command of body movement, they can cause motor symptoms, including weakness or paralysis, lack of coordination, or trouble with walking. Often, muscle weakness or paralysis affects only one side of the body.
Balance problems. Brain tumors that disrupt the normal control of equilibrium can cause dizziness or difficulty with balance.

Spinal Cord Tumors

The spinal cord is, in part, like a living telephone cable. Lying protected inside the bony spine, it contains bundles of nerves that carry messages between the brain and the body’s nerves, such as instructions from the brain to move an arm or information from the skin that signals pain.

A tumor that forms on or near the spinal cord can disrupt this communication. Often, these tumors exert pressure on the spinal cord or the nerves that exit from it; sometimes, they restrict the cord’s supply of blood. Common symptoms that result from this include: Pain. Normally, the spinal cord carries important warnings about pain from the body’s nerves to the brain. By putting pressure on the spinal cord, a tumor can trigger these circuits and cause pain that feels as if it is coming from various parts of the body. This pain is often constant, sometimes severe, and can have a burning or aching quality.
Sensory changes. Many people with spinal cord tumors suffer a loss of sensation. This usually takes the form of numbness and decreased skin sensitivity to temperature.
Motor problems. Since the nerves control the muscles, tumors that affect nerve communication can trigger a number of muscle-related symptoms. Early symptoms include muscle weakness; spasticity in which the muscles stay stiffly contracted; and impaired bladder and/or bowel control. If untreated, symptoms may worsen to include muscle wasting and paralysis. In addition, some people develop an abnormal walking rhythm known as ataxia.

The parts of the body affected by these symptoms vary with tumor location along the spinal cord. In general, symptoms strike body areas at the same level or at a level below that of the tumor. For example, a tumor midway along the spinal cord (in the thoracic spine) can cause pain that spreads over the chest in a girdle-shaped pattern and gets worse when the individual coughs, sneezes, or lies down. A tumor that grows in the top fourth of the spinal column (or cervical spine) can cause pain that seems to come from the neck or arms. And a tumor that grows in the lower spine (or lumbar spine) can trigger back or leg pain.

In some cases, one or more tumors extend over several sections of the spinal cord. This results in symptoms that are spread over various parts of the body. Sometimes sensory symptoms occur in a patchy, confusing pattern in which some parts of the body are unaffected even though they lie between affected areas.

Doctors divide spinal cord tumors into three major groups based on where they are found. Extradural tumors grow between the bony spinal canal and the tough membrane called dura mater that protects the spinal cord. Tumors inside the dura (intradural tumors) are further divided into those outside the spinal cord (extramedullary tumors) and those inside the spinal cord (intramedullary tumors).

How Are CNS Tumors Diagnosed?

Research has made major strides in the ability to detect and diagnose CNS tumors. When a doctor suspects a brain or spinal cord tumor because of a patient’s medical history and symptoms, he or she can turn to a number of specialized tests and techniques to confirm the diagnosis. However, the first test is often a traditional neurological exam. A neurological exam checks:

Eye movement, eye reflexes, and pupil reaction. For example, the doctor can shine a pen light into the eye to see if the pupil contracts normally or ask the patient to follow a moving object, such as a finger. Reflexes. Tests like tapping below the knee with a rubber hammer can identify changes in reflexes. Hearing. Using a tuning fork, the physician can check for changes in hearing. Sensation. The doctor can use something sharp like a pin to test the sense of touch. Movement. Problems with movement are often tested by asking the patient to move his or her tongue, head, or facial muscles . as in smiling . and to perform tasks with the arms and legs. Balance and coordination. Typical tests include maintaining balance with the eyes closed, walking heel-to-toe in a straight line, or touching the nose with the eyes closed.

The next step in diagnosing brain tumors often involves X-rays or special imaging techniques and laboratory tests that can detect the presence of a tumor and provide clues about its location and type.

Imaging and X-rays

Special imaging techniques developed through recent research, especially computed tomography (CT) and magnetic resonance imaging (MRI), have dramatically improved the diagnosis of CNS tumors in recent years. In many cases, these scans can detect the presence of a tumor even if it is less than half-an-inch across.

CT uses a sophisticated X-ray machine and a computer to create a detailed picture of the body’s tissues and structures. Often, doctors will inject a special dye into the patient before performing a CT scan. The dye, also called contrast material, makes it easier to see abnormal tissue. A CT scan often gives doctors a good idea of where the tumor is located in the brain or spinal cord and can sometimes help them determine the tumor’s type. It can also help doctors detect swelling, bleeding, and other associated conditions. In addition, CT scans can help doctors check the results of treatment and watch for tumor recurrence.

MRI uses a magnetic field and radio waves, rather than X-rays, and can often distinguish accurately between healthy and diseased tissue. MRI gives better pictures of tumors located near bone than CT, does not use radiation as CT does, and provides pictures from various angles that can enable doctors to construct a three-dimensional image of the tumor.

A third imaging technique called positron emission tomography (PET) provides a picture of brain activity rather than structure by measuring levels of injected glucose (sugar) that has been labelled with a radioactive tracer. Glucose is used by the brain for energy. Detectors placed around the head can spot the labelled glucose, and a computer uses the pattern of glucose distribution to form an image of the brain. Since malignant tissue uses more glucose than normal, it usually shows up on the scan as brighter or lighter than surrounding tissue. Currently, PET is not widely used in tumor diagnosis, in part because the technique requires very elaborate, expensive equipment, including a cyclotron to create the radioactive glucose.

Although it is not widely used for diagnosis now that CT and MRI scans are possible, angiography continues to help doctors distinguish certain types of brain tumors and make decisions about surgery. In angiography, doctors inject dye into a major blood vessel, usually one of the large arteries in the neck. This dye deflects X-rays and makes it possible for doctors to see the network of blood vessels by taking a series of X-ray pictures as the dye flows through the brain. Since some tumors have a characteristic pattern of blood vessels and blood flow, the pictures can provide clues about the tumor’s type. Information from angiography can also tell physicians if a tumor is located close to important, normal blood vessels that must be avoided during surgery.

Widespread use of CT and MRI has largely displaced use of traditional X-rays for diagnosis of brain and spinal cord tumors, since X-rays do not provide very useful images of brain tissue. They are occasionally helpful when tumors cause changes in the skull or spinal cord or when they contain tiny deposits of bone-like material made of calcium.

Physicians may also use a specialized X-ray technique, called a myelogram, when diagnosing spinal cord tumors. In myelography, a special dye that absorbs X-rays is injected into the spinal cord. This dye outlines the spinal cord but will not pass through a tumor. The resulting X-ray picture shows a dark area or narrowing that reveals the tumor’s location.

Laboratory Tests

Laboratory tests commonly used include the electroencephalogram (or EEG) in patients whose tumors cause epilepsy and lumbar puncture, also known as the spinal tap. The EEG uses special patches placed on the scalp or fine needles placed in the brain to record abnormal electrical currents inside the brain.

In lumbar puncture, doctors obtain a small sample of cerebrospinal fluid. This fluid can be examined for abnormal cells or unusual levels of various compounds that suggest a brain or spinal cord tumor.

In the future, diagnosis of brain tumors should grow more accurate as additional techniques, including new ways to image the CNS and advanced laboratory tests, are developed through basic laboratory studies and clinical research.

What is a Biopsy and How is it Used?

A biopsy is a surgical procedure in which a small sample of tissue is taken from the suspected tumor, often during surgery aimed at removing as much tumor as possible.

A biopsy gives doctors the clues they need to specifically diagnose the type of tumor. By examining the sample under a microscope, the pathologist, a physician who specializes in understanding how disease affects the body’s tissues, can tell what kinds of cells are in a tumor. Pathologists also look carefully for certain changes that signal cancer. These signs include abnormal growths or changes in the cell membranes and telltale problems in the cell nuclei, which normally control cell characteristics and growth. For example, cancerous cells may grow small finger-like projections on their normally smooth surface or have extra nuclei.

Using this information, the pathologist provides a diagnosis of the tumor type. The tumor may also be classified as benign or malignant and given a numbered score that reflects how malignant it is. This score can help doctors determine how to treat a tumor and predict the likely outcome, or prognosis, for the patient.

Although biopsy has long been a mainstay of brain tumor diagnosis, it is still an important research area. Scientists continue to look for better ways to identify and classify types of abnormal cells in order to improve the accuracy of prognosis and provide the best possible information for treatment decisions.

How Are Brain and Spinal Cord Tumors Treated?

The three most commonly used treatments, surgery, radiation, and chemotherapy, are largely the result of recent research. For some patients, doctors may suggest a new treatment still being tested. In any case, the doctor will recommend a treatment or a combination of treatments based on the tumor’s location and type, any previous treatment the patient may have received, and the patient’s medical history and general health.

Surgery

Surgery to remove as much tumor as possible is usually the first step in treating an accessible tumor, that is, a tumor that can be removed without unacceptable risk of neurological damage. Fortunately, research has led to advances in neurosurgery that make it possible for doctors to reach many tumors that were previously considered inaccessible. These new techniques and tools equip neurosurgeons to operate in the tight, vulnerable confines of the CNS. Some recently developed approaches in use in the operating room include: Microsurgery. In this widely used technique, the surgeon looks through a high-powered microscope to get a magnified view of the operating area. This makes it easier to seeand removetumor tissue while sparing surrounding healthy tissue.
Stereotaxic procedures. In these procedures, a computer uses information from CT or MRI to create a three-dimensional map of the operation site. The computer uses the map to help the surgeon guide special, computer-assisted tools. This makes it possible for surgeons to approach certain difficult-to-reach tumors with greater precision. Many procedures can be performed using this approach, including biopsy, certain types of surgery, and planting radiation pellets in a tumor.
Ultrasonic aspirators. Ultrasonic aspirators use sound waves to vibrate tumors and break them up. Like a vacuum, the aspirator then sucks up the tumor fragments.
Evoked potentials. Doctors use this test during surgery to determine the role of specific nerves and thus avoid damage. In this technique, small electrodes are used to stimulate a nerve so its electrical response, or evoked potential, can be measured.
Shunts. Shunts are flexible tubes used to reroute and drain fluid. Doctors sometimes insert a shunt into the brain when a tumor blocks the flow of cerebrospinal fluid and causes hydrocephalus. Shunting of the fluid can relieve headaches, nausea, and other symptoms caused by too much pressure inside the skull.

Surgery may be the beginning and end of treatment if the biopsy shows a benign tumor. If the tumor is malignant, however, doctors often recommend additional treatment following surgery, including radiation, chemotherapy, or experimental treatments.

An inaccessible or inoperable tumor is one that cannot be removed surgically because of the risk of severe nervous system damage. These tumors are frequently located deep within the brain or near vital structures such as the brain stem, the part of the brain that controls many crucial functions including breathing and heart rate. Malignant, multiple tumors may also be inoperable. Doctors treat most malignant, inaccessible, or inoperable CNS tumors with radiation and/or chemotherapy.

Among patients who have metastatic CNS tumors, doctors usually focus on treating the original cancer first. However, when a metastatic tumor causes serious disability or pain, doctors may recommend surgery or other treatments to reduce symptoms even if the original cancer has not been controlled.

Radiation Therapy

In radiation therapy, the tumor is bombarded with beams of energy that kill tumor cells. Traditional radiation therapy delivers radiation from outside the patient’s body, usually begins a week or two after surgery, and continues for about 6 weeks. The dosage is fairly uniform throughout the treated areas, making it especially useful for tumors that are large or have infiltrated into surrounding tissue.

However, when traditional radiation therapy is given to the brain, it may also cause damage to healthy tissue. Depending on the type of tumor, doctors may be able to choose a modified form of radiation therapy to help prevent this and to improve the effectiveness of treatment. Modifying therapy can be as simple as changing the dosage schedule and amount of radiation that a patient receives. For example, an approach called hyperfractionation uses smaller, more frequent doses. Neurological investigators are also testing several other, more complex techniques to improve radiation therapy.

Chemotherapy

Chemotherapy uses tumor-killing drugs that are given orally or injected into the bloodstream. Because not all tumors are vulnerable to the same anticancer drugs, doctors often use a combination of drugs for chemotherapy.

Chemotherapeutic drugs generally kill cells that are growing or dividing. This property makes them more deadly to malignant tissue, which contains a high proportion of growing and dividing cells, than to most normal cells. It also causes some of the side effects that can accompany chemotherapy, such as skin reactions, hair loss, or digestive problems, because a high proportion of these normal cell types are also growing and dividing at any given time. The drugs most commonly used for CNS tumors are known by the initials BCNU (sometimes called carmustine) and CCNU (or lomustine). Research scientists are also testing many promising drugs to learn if they can improve treatment for brain and spinal cord tumors and reduce side effects.

Other Drugs

Tumors, surgery, and radiation therapy can all result in swelling inside the CNS. Doctors may prescribe steroids for short or long periods to reduce this swelling. Examples of such drugs include dexamethasone, methylprednisolone, and prednisone.

Whether new treatment approaches involve surgery, radiation therapy, chemotherapy, or completely new avenues to treating CNS tumors, carefully planned clinical trials of new and experimental therapies are vital for identifying promising treatments and learning the best applications of current therapies. Experimental treatments, in turn, would not be possible without research by basic and clinical scientists who identify new approaches.

Where Should Patients Go For Treatment?

Brain and spinal cord tumors are often difficult to diagnose, and surgery to remove them demands great skill. Experience, therefore, is probably the most important factor in choosing among physicians. Brain and spinal cord tumors are also relatively rare. Many physicians see only a few patients with CNS tumors each year. Others, however, have made treating brain and spinal cord tumors their specialty. Patients should consider how many patients a physician treats each year. Because many patients are understandably perplexed or frightened by a CNS tumor diagnosis, it is also important that they choose a physician who will answer questions and describe treatment options clearly and fully.

Patients should also learn what techniques and tools are available at the physician’s hospital. Teaching hospitals affiliated with a medical college or university are more likely to be involved in research and, thus, have the equipment and specialists necessary to offer experimental treatments. Finally, if a patient is dissatisfied with a physician or a physician’s recommendations, he or she may wish to seek another opinion.

The voluntary organizations listed on the pocket card at the back of this publication may be able to help in locating physicians who specialize in treating brain tumors, as well as provide information about CNS tumors.

What Research is Being Done?

Scientists are attacking CNS tumors through biomedical research to improve medical understanding and treatment. CNS tumor research ranges from bench-side studies on the origins and characteristics of tumors to bed-side studies that test new tumor-killing drugs and other innovative treatments. Much of this work is supported by the National Institute of Neurological Disorders and Stroke (NINDS) and by the National Cancer Institute (NCI), as well as other agencies within the Federal Government, non-profit groups, and private institutions.

Some key areas of brain tumor research include:

Radiosurgery. In radiosurgery computerized localization techniques permit delivery of a very large dose of radiation to a well-defined, precisely targeted region. This technique can deliver a large dose of radiation to the tumor while minimizing radiation of normal tissue. Through research, scientists thus far have found that radiosurgery is most useful for small tumors that do not invade the brain and that are difficult to remove surgically. Research scientists continue to examine whether this technique can help patients with other tumor types as well.

Drugs and techniques for chemotherapy. Dozens of new chemotherapeutic drugs are in various stages of development. Scientists are testing these drugs in animals and patients to determine what side effects they cause, what doses are appropriate, and whether they can improve survival and recovery. Patients interested in up-to-date information on current trials are encouraged to contact the resources listed on the pocket card at the end of the brochure.

Scientists are also working to overcome an obstacle to effective chemotherapy for brain and spinal cord tumors, the blood-brain barrier. The blood-brain barrier, an elaborate meshwork of fine blood vessels and cells that filters blood reaching the CNS, normally helps protect the sensitive tissues of the CNS from potentially dangerous compounds in the bloodstream and changes in its environment. But the blood-brain barrier also stymies many efforts to deliver anticancer drugs that may help patients with CNS tumors. Investigators are testing drugs that may help open the barrier. If these drugs prove useful and safe in animal models and humans, then physicians would be equipped to test promising anticancer drugs that normally cannot cross the blood-brain barrier.

Another experimental path aimed at improving drug delivery into the CNS is called interstitial chemotherapy. With this technique a slow infusion into the interstitial spaces of the tumor permits delivery of large molecules to the tumor. In another technique, doctors place disc-shaped specially designed polymers, wafers soaked with chemotherapeutic drugs, directly into tumor tissue. These techniques may help physicians increase the dose of life-prolonging drugs while limiting side effects, since less of the drug spreads elsewhere in the body. Most trials of these technique currently involve patients with recurrent gliomas.

Drugs to improve radiation therapy. Many scientists are testing the usefulness of drugs known as radiosensitizers that make tumor tissue more vulnerable to radiation. Early results with the two most commonly studied radiosensitizers, metronidazole and misonidazole, have been mixed; some trials suggest these drugs may improve survival in certain patients, while other trials have shown little benefit.

Gamma knife. The gamma knife, used for a procedure known technically as stereotactic gamma knife radiosurgery, combines precise stereotactic guidance and a sharply focused beam of radiation energy to deliver a single, precise dose of radiation. Despite its name, the gamma knife does not require a surgical incision. Investigators using this tool have found it can help them reach and treat some small tumors that are not accessible through surgery.

Gene therapy. Gene therapy, an innovative approach to treating CNS cancer, is in the early stages of research in laboratories around the country. Genes are the blueprints the body’s cells use to make proteins and other vital substances. In gene therapy, scientists insert a new gene into specific cells. In the case of gene therapy for brain tumors, this inserted gene could make the tumor cells sensitive to certain drugs, program the cancerous cells to self-destruct, or instruct them to manufacture substances that would slow their growth. Scientists are using tumor cells and animal models to learn how various genes, once introduced, hinder cancer growth and to identify the best methods for inserting new genes into tumor cells.

Hyperthermia. Tumors are more sensitive to heat than normal tissue, partly because they have less blood flow to cool them. Research scientists testing hyperthermia take advantage of this sensitivity by placing special heat-producing antennae into the tumor region after surgery. Most often, these antennae send out microwaves that raise the temperature in nearby tissues. Hyperthermia is a new treatment for tumors in the brain, and scientists are still testing its effectiveness. They are also looking at heat sources that may be more effective than microwaves, including electromagnetic energy and radiofrequencies.

Immunotherapy. The body’s immune system normally seeks out and destroys foreign tissue such as cancerous cells by detecting antigens, telltale proteins found on foreign cells that alert the body to the foreign cells’ presence. Stimulated by the antigens, the body manufactures a variety of immune cells and special proteins called antibodies. These antibodies then latch onto the antigens, working as tiny flags that alert immune cells to attack and destroy the foreign cells. In immunotherapy, an exciting and very new field of CNS tumor research, scientists are looking for ways to duplicate or enhance the body’s immune response to fight against brain and spinal cord cancer.

Some scientists are testing the effectiveness of giving the body’s immune system a general boost. Much like the way coffee can stimulate the nervous system, certain naturally occurring body chemicals trigger immune cells to grow and divide. In numerous studies, researchers have supplied patients with extra amounts of immune stimulants, such as interleukin-2, in the hope that they will improve the body’s ability to fight CNS cancer. However, this technique has produced mixed results. A second type of general immunotherapy involves removing immune cells from a patient, growing and activating these cells and then returning them to the patient where they can work against the cancer. This approach has also yielded mixed results.

Another, still more recent approach in immunotherapy research specifically targets tumor cells using monoclonal antibodies. Like duplicate keys for the same lock, monoclonal antibodies are multiple copies of a single antibody; they fit one, and only one, antigen. Scientists are now producing monoclonal antibodies against tumor cell antigens and testing their usefulness. For example, scientists at the NINDS and elsewhere are linking these antibodies to toxins that can kill tumor cells. The armed monoclonal antibodies then function like guided missiles; they seek out the tumor cells with a matching antigen, bind to these tumor cells, and deliver their toxin. Early experiments with this therapy suggest it has more promise for treating widespread cancer cells than solid tumors. Studies are underway to corroborate these early results and to learn if this therapy has promise for other types of CNS tumors. Monoclonal antibodies may also prove helpful in improving brain tumor diagnosis, because they can be attached to special tracers to make tumor cells more visible.

Intraoperative ultrasound. This technique, which uses sound waves, provides the surgeon with an image of brain tissues during the operation. Ultrasound is less expensive and complex than other imaging techniques. Some scientists conducting research on intraoperative ultrasound have found the technique makes it easier for the surgeon to locate the outer edges of tumor tissue, which can be hard to find. Thus, this technique may help improve tumor surgery by increasing the amount of tumor that can be safely removed.

Oncogenes. The body contains a number of genes that are important in normal cell growth and development. Changes in some of these genes . which might be triggered by such events as exposure to chemicals or radiation . can transform them into dangerous, cancer-causing oncogenes. A number of oncogenes have already been found, and scientists continue to look for more. They are also working to identify specific events that can create oncogenes and to learn if there may be ways to prevent oncogenes from forming or to impair oncogene function in cancerous cells.

PET. Based on recent research, some scientists believe that PET scans offer important clues for diagnosis of brain tumors. For example, physicians sometimes have trouble detecting recurrent tumors with CT or MRI scans. Recent studies have shown that PET may make it easier to detect recurrent brain tumors. Scientists are also examining whether PET can help physicians tell the difference between benign and malignant tumors before performing a biopsy or surgery.

Physiological mapping. Mapping brain functions has promise for improving the safety and effectiveness of brain tumor surgery, particularly when the tumor lies in or next to in critical brain regions. In physiological mapping, the physician locates brain areas responsible for key functions, such as language or sensation. The surgeon then has a map to help avoid these critical areas, thus reducing the chance of serious complications.

Photodynamic therapy. Photodynamic therapy uses drugs that collect in tumor cells and can be turned on or activated by special light. The drugs may be given by injection or placed directly into the tumor during an initial surgery. In order to activate the tumor-killing drug, the physician must expose the tumor tissue to light during surgery. Thus far, this technique has been found useful only for small amounts of tumor tissue, although researchers continue the search for new light-sensitive drugs and better light sources that can penetrate tumors.

Tumor growth factors. Cancerous tumors are often rich in an array of substances, called growth factors, that enable them to grow and spread rapidly. In recent years, scientists have identified a number of these factors, including one that triggers growth of nerve tissue and another that stimulates blood vessels to grow. Many investigators continue the search for more such factors. Meanwhile, other researchers have begun testing antibodies that can block these factors. Early results in animals have shown that blocking growth factors with antibodies may help slow tumor growth, suggesting this research arena could lead to new therapies for brain tumors.

Although many new approaches to treatment thus appear promising, it is important to remember that all potential therapies must stand the tests of well-designed, carefully controlled clinical trials and long-term follow-up of treated patients before any conclusions can be drawn about their safety or effectiveness.

Past research has led to improved tumor treatments and techniques, providing longer survival and richer lives for many CNS tumor patients. Current research promises to generate further improvements. In the years ahead, physicians and patients can look forward to new forms of therapy developed through an understanding of the unique traits of CNS tumors.

Where Can I Find More Information?

The NINDS is the Federal Government’s leading supporter of biomedical research on nervous system disorders, including brain and spinal cord tumors. The NINDS conducts research on brain tumors in its own laboratories at the National Institutes of Health (NIH) in Bethesda, MD, and supports research at institutions worldwide. The Institute also sponsors an active public information program. Other NINDS publications that may be of interest to those concerned about brain and spinal cord tumors include "Epilepsy: Hope Through Research," and the fact sheets, "Neurofibromatosis" and "Tuberous Sclerosis."
For more information, contact the Institute’s Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 13050
Silver Spring, Maryland 20911
(800) 352-9424

The National Cancer Institute (NCI), also within the NIH, is the Federal Government’s leading supporter of cancer-related biomedical research. NCI offers a variety of publications and a toll-free cancer information service. For more information, write or call:

Office of Cancer Communications
National Cancer Institute
Building 31, Room 10A03
31 Center Drive, MSC 2580
Bethesda, MD 20895-2580
(301) 435-3848


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