Brain Tumors: Primary

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Brain Tumors: Primary

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WHAT ARE BRAIN TUMORS?

Brain tumors are composed of cells that exhibit unrestrained growth in the brain. They can be benign (noncancerous, meaning that they do not spread elsewhere or invade surrounding tissue) or malignant (cancerous).

Malignant brain tumors are further classified as either primary or secondary tumors. Primary tumors start in the brain, whereas secondary tumors spread to the brain from another site such as the breast or lung. (in this report, the term "brain tumor" will refer mainly to primary malignant tumors, unless they are specifically defined as benign or secondary.)

Benign Tumors

Benign tumors represent half of all primary brain tumors. Their cells look normal, grow slowly, and do not spread (metastasize) to other sites in the body. Benign tumors can still be serious and even life-threatening if they are situated in vital areas in the brain where they exert pressure on sensitive nerve tissue or if they increase pressure within the brain. While some benign brain tumors may pose a health risk, including risk of disability and death, most are usually successfully treated with techniques such as surgery.

Secondary (Metastatic) Malignant Brain Tumors

A secondary (metastatic) brain tumor occurs when cancer cells spread to the brain from a primary cancer in another part of the body. Secondary tumors are about three times more common than primary tumors of the brain. Usually, multiple tumors develop. Solitary metastasized brain cancers may occur but are less common. Most often, cancers that spread to the brain to cause secondary brain tumors originate in the lung, breast, kidney, or from melanomas in the skin.

Primary Malignant Brain Tumors

A primary malignant brain tumor is one that originates in the brain itself. Although primary brain tumors often shed cancerous cells to other sites in the central nervous system (the brain or spine), they rarely spread to other parts of the body.

Brain tumors are generally named and classified according to the following:

the normal brain cells from which they originate, or
the location in which the cancer develops.

The biologic diversity of these tumors, however, makes classification difficult, and some experts believe that more specific categories are needed. [For a description of these tumors, see table, Common Brain Tumors .]

Categories of Primary Glioma Brain Tumors by Cell Types

About half of all primary brain tumors are known collectively as gliomas. They are cancerous forms of glial cells, which are the building-block cells of the connective, or supportive, tissue in the central nervous system. There are several glial cells types from which gliomas form and are named:

Astrocytomas are primary brain tumors derived from astrocytes, which are star-shaped glial cells. Astrocytes provide nutrients, support, and insulation for nerve cells and are one of the primary neurologic cells in the body.
Oligodendrogliomas develop from oligodendrocyte glial cells. These tissues form the protective coatings around nerve cells. Although these tumors were thought to represent about 5% of all gliomas, more recent evidence suggests they may comprise about 20% of gliomas. Pure oligodendrogliomas, however, are rare and in most cases they occur in mixed gliomas. ( See below ).
Ependymomas are derived from ependymal cells. These cells line the ventricles (fluid-filled cavities) in the lower part of the brain and the central canal of the spinal cord. They constitute about 6% of all gliomas.
Mixed Gliomas contain a mixture of malignant gliomas. About half of these tumors contain both cancerous oligodendrocytes and astrocytes.

It should be noted that gliomas may also contain cancer cells derived from brain cells other than glial cells. [For a description of these tumors, see table, Common Brain Tumors .]

Categories of Brain Tumors by Location

Some brain tumors are categorized by their location in the brain. Such tumors often contain gliomas but are also frequently a mixture of different cell types. [For a description of these tumors, see table, Common Brain Tumors .]

Meningiomas. Meningiomas are usually benign tumors that develop in the membranes that cover the brain and spinal cord (the meninges). They are not technically classified as brain tumors but they have similar symptoms and develop within the brain, and so in practical terms, they are considered to be brain tumors. In fact, they comprise 20% of all primary brain tumors. They occur more often in women than in men. Most grow very slowly, and the majority of people who have them never know they are present. Malignant forms called anaplastic meningiomas and hemangioperictyomas are less common and are difficult to remove surgically.

Cerebellar Astrocytomas. Gliomas that develop inside the brain usually occur in the cerebral hemispheres (the right and left sides of the brain). In such cases, they are referred to by their location, cerebellar astrocytomas.

Brain Stem Gliomas. Brain stem gliomas develop in the lowest portion of the brain. The brain stem connects the cerebrum (the higher centers of the brain) to the spinal cord. The brain stem is thought to be the primitive brain because it controls the most basic functions. It consists of three primary parts:

The medulla, which regulates breathing, swallowing, blood pressure, and heart rate.
The pons (meaning "bridge") that links the cerebellum to the cerebrum.
The midbrain, which helps control vision and hearing.

Medulloblastomas. Medulloblastomas are always located in the cerebellum, which is at the base and toward the back of the brain. They represent about 3% of all brain tumors.

Pituitary Tumors. Pituitary tumors comprise about 10% of primary brain tumors and are benign, slow-growing masses in the pituitary gland.

Other Brain Tumor Locations. Optic nerve gliomas occur in the optic nerve, which is located behind the eye. Acoustic neuromas make up 7.5% of brain tumors.

COMMON BRAIN TUMORS

Some Common Brain Tumors
Brain Tumor	Grade and Subtype (if relevant)	Description	Usual Treatment
Cell Types
Astrocytomas Derived from star-shaped glial cells called astrocytes.	Low-Grade (Usually I) Astrocytomas. Pilocytic gliomas.	Tumors are well differentiated. Cells are relatively normal and rarely metastasize. They grow relatively slowly. Pilocytic astrocytomas have the highest 5-year survival rates (greater than 70%). However, even well differentiated astrocytomas are life threatening if they are inaccessible. Pilocytic gliomas occur mostly in children.	Cancer may sometimes be completely removed through surgery, particularly if it occurs in the cerebellum. For recurrence or residual tumors, reoperation or radiotherapy may be given. Repeat surgery for cerebellar astrocytoma is often very successful. For those who fail radiotherapy and chemotherapy, investigative drugs are used.
	Low-Grade (II) Astrocytomas . Fibrillary, protoplasmic, and protoplasmic astrocytomas. Some pleomorphic xanthoastrocytomas.	Tumors are well differentiated. Cells are relatively normal and less malignant than those in higher grades. They grow relatively slowly but can spread. Survival rates average five years but people can survive for a decade or more. Pleomorphic xanthoastrocytomas have a relatively favorable prognosis, but can recur and demonstrate aggressive clinical behavior. Low-grade astrocytomas generally occur in young adulthood, with a peak incidence in 30s and 40s.	Surgery, if possible, plus radiotherapy. Surgery alone in certain children, if possible. Trials on following: Radiotherapy with or without chemotherapy; Low-versus-high radiotherapy doses (studies suggest results are the same and high-dose causes more side effects); Deferring radiotherapy until tumor progresses and symptoms occur (studies suggest survival rates are the same).
	Malignant (High-grade III and IV) Astrocytomas. Anaplastic astrocytoma (gemistocytic and some pleomorphic xanthoastrocytomas). Usually mid-grade (III).	Tumors grow more rapidly than lower grades and infiltrate other nearby healthy cells. Not well-differentiated. Five year survival rates are about 30%.	Treatment same for all malignant astrocytomas. Surgery, with removal of as much of tumor as possible followed by radiotherapy, with or without chemotherapy. (Chemotherapy appears to improve survival rates. Carmustine most effective agent at this time.) For recurrence, surgery, if possible, stereotactic radiosurgery, investigative chemotherapy agents. Trials include: Advanced radiotherapy techniques. New drugs such as temozolomide, monoclonal antibodies; Intraarterial chemotherapy.
	Glioblastoma multiforme (also called GBM or glioblastomas). High-grade (IV and V).	Very rapidly growing, tumors; spread quickly. Median survival times are 17 to 157 weeks depending on grade and treatments. Represents about 30% of all primary brain tumors. Most common in older adults (over 55) and affect more men than women.

Brain Tumor	Grade and Subtype (if relevant)	Descriptions	Usual Treatment
Cell Types
Ependymomas Derived from glial cells that line the ventricles (fluid-filled brain cavities) and spinal cord central canal. Do not usually spread into normal brain tissue. Can block exits for cerebrospinal fluid and cause hydrocephalus. Ependymomas in general comprise 10% of all childhood brain tumors. Can also affects adults.	Myxopapillary ependymoma (found in the spine). Subependymoma (found in one of the ventricles). Grade depends on location of the tumor and whether it is in the spinal fluid. Low-grade (I).	No or very slow growth. In addition to grade, risk is also based on location of the tumor. Tumors on the spinal cord are more accessible than those in the fourth ventricle or in the middle of the lower back portion of the brain.	Can often be removed and cured with surgery, particularly those on spinal cord. Radiation may be needed.
	Papillary, cellular, and clear cell ependymomas. Low-grade (II). s.	Slow growth. Usually affect adults.	Surgery alone or followed by radiotherapy. For those who fail radiotherapy, possible use of nitrosourea-based chemotherapies or investigative drugs.
	Anaplastic ependymomas. Grade III.	Spread to the spinal fluid.	Surgery followed by radiotherapy to brain and spinal cord. Possible shunt.
	Primitive neuroecto-dermal Tumor (PNET). Composed of malignant forms of early, undeveloped nerve cells called neuroblasts. Grade IV.	Primitive nerve cells that grow very rapidly. Usually occur in cerebellum. Very rare, but more common in children.	Surgery followed by radiotherapy to brain and spinal cord. Chemotherapy in young children.

Brain Tumor	Grade (if relevant)	Description	Usual Treatment
Cell Types
Oligodendrogliomas Pure cell types are rare. Most often occur in mixed gliomas.	Categorized as either low- or high-grade. Most are low grade II	Low grade difficult to tell from astrocytomas, although they are usually calcified. Very likely to bleed. Usually spread along nerve pathways of the brain and spine and rarely outside this area. In spite of difficulty in removing surgically, in some patients survival can be 30 to 40 years. Usually have better prognosis than astrocytomas of equal grade. Occur mostly in middle-aged adults, although there is also a small peak in incidence in children.	Treatment usually delayed until progression causes symptoms. Surgery followed by radiotherapy for well-differentiated tumors, but surgery usually difficult. These tumors are very responsive to chemotherapy, particularly a regimen called PCV. Radiotherapy equally effective but has more side effects. Sustained remissions averaging 16 years often achieved. Trials of additional chemotherapy for less well-differentiated tumors or for residual tumors after surgery.
		High-grade, anaplastic oligodendrogliomas	Immediate treatment. Surgery, if possible. Same chemotherapy treatments as for low-grade tumors followed by radiotherapy. Possible additional agents include melphalan, thiotepa, temozolomide, carboplatin, cisplatin, and etoposide.
Mixed Gliomas Oligo-astrocytoma, anaplastic olig-astrocytoma, and others.	Grade determined by the highest-grade cell present in the tumor.		Same as for oligodendroglioma.

Some Common Brain Tumors
Brain Tumors By Location	Description	Usual Treatment
Meningiomas	They are usually benign and are rarely invasive. In such cases long-term outlook is very favorable. (Malignant forms, anaplastic meningiomas and hemangioperictyomas are uncommon and occur in about 2% of cases.)	Usually watchful waiting. Surgery the treatment of choice, if possible, although 20% recur after 10 years. Malignant forms and those at the base of the skull difficult to impossible to remove surgically. Stereotactic radiosurgery or fractionated external beam radiotherapy showing promising results for some patients.
Cerebellar astrocytomas (located in cerebellum)	Located in the cerebellum. Usually low-grade but depends on cell type. If surgical removal is complete, up to 90% survival rates. More common in children than adults.	Surgery primary treatment. Radiotherapy if removal is incomplete.
Brain Stem Gliomas	About 60% and 70% of brain stem tumors are diffuse, which are likely to spread and have a rapid onset of symptoms. Focal tumors tend to be solid or cyst-like; they generally develop gradually. Occurs in both children and young adults.	Tumors in this area are rarely removed surgically since the nerve tissue in this area is responsible for vital life functions. Slow-growing tumors may only require watchful waiting. Trials using advanced radiotherapy techniques, gene therapy, immunotherapy, and other experimental drugs.
Medulloblastomas	Usually fast-growing aggressive cells. Often spreads to other parts of central nervous system or meninges (membranes around the brain and spinal column). In children, with aggressive therapy, 5-year survival rates between 60% and 80% have been reported. In patients who survive for two years after diagnosis, long-term survival rate is nearly 80%. Most common in children and young adults. Cause between 15% and 20% of brain tumors in this patient population.	Treatment is usually surgery and radiotherapy with or without chemotherapy.
Optic Tract Gliomas	Spread along the optic nerve. Usually slow growing. Most often in children under 10. Children with these tumors often have vision and hormonal problems.	Usually surgery if one eye is involved. Possible chemotherapy or radiation.

WHAT ARE THE SYMPTOMS OF BRAIN TUMORS?

Brain tumors produce a variety of symptoms ranging from headache to stroke. They are great mimics of other neurologic disorders. Symptoms occur if the tumor directly damages the nerves in the brain or central nervous system or if its growth imposes pressure on the brain. Some gliomas develop gradually and symptoms may be subtle for a long time, making an early diagnosis difficult.

Headache

Headache is probably the most common symptom of a brain tumor. It should be strongly emphasized, however, that most headaches do not represent an underlying brain tumor Headaches caused by brain tumors may vary depending on the location, and can include some of the following features:

Steady and worse upon waking in the morning and clears up within a few hours.
Persistent non-migraine headache that occurs while sleeping and is also accompanied by at least one other symptom (eg, vomiting, confusion).
May or may not be throbbing, depending on location of the tumor.
Accompanied by double vision, weakness, or numbness.
May worsen with coughing or exercise or with a change in body position.
Sometimes accompanied by neck pain.

Gastrointestinal Symptoms

Gastrointestinal symptoms, including nausea, are also common. Nausea and vomiting, in fact, often occur in children with brain tumors and in all people with brain stem cell tumors.

Seizures

Seizures occur in between 15% and 95% of patients, depending on the location of the tumor.

Tumors are more likely to be localized and affect one area of the brain. In such cases they can cause partial seizures . In this case, a person does not lose consciousness but may experience confusion, jerking movements, tingling, or odd mental and emotional events.
Generalized seizures , which can cause loss of consciousness, are less common, since they are caused by disturbances of nerve cells in diffuse areas of the brain.

Mental Changes

Sometimes the only symptoms are mental changes, which may include the following:

memory loss,
impaired concentration,
problems with speech and reasoning, and
increased sleep.

Other Significant Symptoms

Other important symptoms include the following:

Gradual loss of movement or sensation in an arm or leg.
Unsteadiness.
Unexpected visual disturbance (especially if it is associated with headache), including vision loss (usually of peripheral vision) in one or both eyes or double vision.
Hearing loss with or without dizziness.
Speech difficulty.

Symptoms Associated with Specific Tumors

Specific symptom syndromes may help identify the tumor. The following are some examples.

Symptoms of Brain Stem Gliomas. Sudden onset of symptoms that include vomiting (usually just after waking), a clumsy walk, muscle weakness on one side of the face, difficulty in swallowing, slurred or nasal speech, as well as impaired hearing or vision.

Symptoms of Glioblastoma Multiforme. Rapid onset and worsening of symptoms that include headaches, seizures, memory loss, and changes in behavior.

Life-Threatening Syndromes

Symptoms of brain tumors that indicate an emergency condition requiring prompt intervention include the following:

Pupil dilation.
A fixed gaze.
Paralysis on one or both sides of the body.
Blindness or defective vision in one eye.

WHO GETS BRAIN TUMORS?

General Risk Factors

Primary brain tumors are very uncommon and are expected to develop in about 17,000 Americans over the course of a year. Primary malignant brain tumors represent only 1.3% of all cancers diagnosed in the United States and 2.4% of all deaths due to cancer. Men are at higher risk for most brain tumors than women are.

Primary brain cancers are rare, occuring in slightly more than 11 people per 100,000 per year. There has been some evidence of a growing incidence of brain cancer among the elderly since the 1980s. This increase is most likely due to the fact that people are surviving more common illnesses and some are living long enough to develop these relatively rare cancers.

Age

Although about 90% of primary brain tumors occur in adults, they can develop at all ages, usually peaking in two age groups:

In adults between the ages of 55 and 65.
In children between the ages of three and 12.

Risk Factors in Children. Tumors in the central nervous system are now the most common cancers in children, but they are still rare. About 1,500 children are diagnosed with brain tumors each year, although half are benign. Brain tumors in children are more likely to occur in the cerebellum, the midbrain, or the optic nerve.

The incidence has increased over the past years, but there is some evidence that this increase is only due to better diagnostic procedures. The mortality rate has actually decreased. Researchers have attempted to uncover risk factors for childhood brain cancer. Some association between a higher risk and the following conditions have been observed:

Having well-educated parents.
Having older fathers. (Older fathers may have more genetic mutations in their sperm than younger fathers. Older fathers are also associated with higher socioeconomic groups, which may partly explain the higher incidence of these cancers in children of well-educated parents.)
Children treated with radiation to the head for leukemia and who have a specific genetic defect may face a high risk for brain cancer. (It should be noted that for children without this defect, the risk is very small.)
Having parents with specific cancers. (According to a 2000 study, having parents with nervous system cancers, colon cancer, or cancer in the salivary glands increased the risk of specific brain tumors in their children.)

Environmental or Occupational Risk Factors

Radiation. The only proven risk factor for brain tumors to date is radiation from ions (such as with radiation treatment.)

Studies on the effects of electromagnetic fields are still unclear. One reported that men whose jobs exposed them to magnetic fields had higher rates for brain cancer, although a more recent one found no risk among workers in the electric utility industry. Cellular phones and other wireless radiofrequency devices have been implicated as well, although, studies in both 2000 and 2001 found no evidence to suggest a higher risk.

Chemical Suspects in Brain Tumors. High exposure to a number of chemicals have been associated with brain tumors, although causal relationships are still not proven:

Vinyl chloride has been associated with brain tumors.
High levels of lead exposure in such occupations as lead smelting, lead-battery manufacturing, printing, and the chemical industry may also increase the risk for brain cancers.
A major study of pesticides is underway, but results are not in yet.

Diseases Associated with Brain Tumors

Epilepsy. Some evidence exists that people with epilepsy are at higher risk for gliomas. This increased risk may be due to both the disease and the treatments for it.

Inherited Disorders. About 5% of primary brain tumors are associated with hereditary disorders. They include the following:

Li-Fraumeni cancer family syndrome.
Tuberous sclerosis.
Von Recklinghausen's disease (neurofibromatosis).
Von Hippel Lindau disease.
Familial polyposis (Turcot's syndrome).
Osler-Weber-Rendu syndrome.

Chicken Pox. Some studies suggest that varicella zoster, the virus that causes chicken pox, is associated with a lower risk for gliomas.

WHAT CAUSES BRAIN TUMORS?

Genetic Factors

A number of genes that cause cancer proliferation (oncogenes) and defects in those that suppress tumors (tumor suppressor genes) may play separate roles in a step-by-step process leading to primary brain cancer. Several avenues of investigation are in progress to determine both basic causes and the triggers for genetic defects.

Specific Genetic Abnormalities. A number of specific brain tumors, including glioblastomas, anaplastic astrocytomas, and medulloblastomas, are the result of abnormal or missing genes:

For example, researchers have discovered a defective gene MMAC1 (Mutated Multiple Advanced Cancers) in the majority of the glioblastomas (although not low-grade gliomas). The MMAC1 gene determines how aggressive a tumor will be.
Another defective gene, known as the Patched 2 gene, which appears to promote tumor growth, has been found in about half of all medulloblastomas.

[For description of these tumors, see table Common Brain Tumors .]

Inherited Genetic Factors. A large population study reported that family clusters of brain cancer occurred in a small fraction of astrocytomas, indicating that inherited factors may play a direct role in some cases.

Acquired Genetic Defects. Genetic abnormalities that cause brain tumors are not usually inherited but mostly occur as a result of environmental insults or other factors that affect genetic materials (DNA) in the cells. Researchers are studying a number of environmental assaults that might trigger brain tumors in susceptible individuals. Among them are the following:

Abnormal development in the womb.
Viruses.
Hormones.
Chemicals.
Ionizing radiation.
Electromagnetic fields.

HOW SERIOUS ARE BRAIN TUMORS?

General Outlook

Primary brain tumors account for only 1.5% of all cancers, but they are the third leading cause of cancer deaths among young male adults (ages 15 through 54) and the fourth cause of cancer deaths among women ages 15 through 34. They are also the second leading cause of cancer deaths in children. It should be strongly noted, however, that they are very rare in people of all ages. Recent advances in surgical and radiation treatments have significantly extended average survival times and can reduce the size and progression of malignant gliomas. Unfortunately, the majority of primary brain tumors, anaplastic astrocytomas and glioblastoma multiforme, are only rarely curable.

The best progress over the recent decades has been made specifically in the following:

Medulloblastomas in both children and adults. Long-term survival rates are now about 60% in children after treatment for medulloblastomas, the most common malignant brain tumor in this age group. (New treatments, however, may significantly improve these rates.)
Nonmalignant astrocytomas and oligodendrogliomas in adults.

In general, studies are reporting that patients who survive the first two years after a diagnosis of a brain tumor have at least a 70% chance of surviving for at least five years.

Specific Effects of Tumors on Function

The specific effects of tumors on the brain can causes seizures, mental changes, and mood, personality, and emotional changes. Such effects can be devastating to the patient and the caregivers. A number of treatments are available that help alleviate these complications, and patients and family members should discuss these with their physician. [ See also What Are Some Treatments for Complications of Brain Tumors?]

HOW ARE BRAIN TUMORS DIAGNOSED?

Neurological Exam

A neurological exam is usually the first test given when a patient complains of symptoms that suggest a brain tumor. The exam includes checking eye movements, hearing, sensation, muscle movement, sense of smell, and balance and coordination. The physician will also test mental state and memory.

Imaging Techniques

X-rays of the skull were once standard diagnostic tools but are now performed only when more advanced procedures are not available. Advanced imaging techniques have dramatically improved the diagnosis of brain tumors in recent years.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is the gold standard for diagnosing a brain tumor. It does not use radiation and provides pictures from various angles that can enable doctors to construct a three-dimensional image of the tumor. It gives a clear picture of tumors near bones, smaller tumors, brainstem tumors, and low-grade tumors. MRI is also useful during surgery to show tumor bulk, for accurately mapping the brain and for detecting response to therapy.

A variant called magnetic resonance spectroscopy (MRS) is capable of providing information on the activity of the brain using magnetic resonance imaging. MRS is proving to be accurate for distinguishing dead (necrotic) tissue caused by previous radiation treatments from recurring tumor cells in the brain, a difficult diagnostic issue.

Computed Tomography. Computed tomography (CT) uses a sophisticated x-ray machine and a computer to create a detailed picture of the body's tissues and structures. It is not as accurate as an MRI and does not detect about half of low-grade gliomas. It is useful in certain situations, however. Often, doctors will inject the patient with an iodine dye, called contrast material, to make it easier to see abnormal tissues. A CT scan helps locate the tumor and can sometimes help determine its type. It can also help detect swelling, bleeding, and associated conditions. In addition, computed tomography is used to check the effectiveness of treatments and watch for tumor recurrence.

Positron Emission Tomography. Positron emission tomography (PET) provides a picture of the brain's activity rather than its structure by tracking substances that have been labeled with a radioactive tracer. PET is not routinely used for diagnosis, but it may supplement MRIs to help determine tumor grade after a diagnosis. As with magnetic resonance spectroscopy (MRS), it is also able to distinguish between recurrent tumor cells from dead cells or scar tissue, although MRS is more widely available.

Other Imaging Techniques. A number of other advanced imaging techniques may be used for specific purposes, if available or under investigation.

Single photon emission tomography (SPECT) is similar to PET but is not as effective in distinguishing tumor cells from destroyed tissue after treatments.
Magnetoencephalography (MEG) scans measure the magnetic fields created by nerve cells as they produce electrical currents.
Cerebral angiography involves x-rays of blood vessels in the brain. A long, thin tube (catheter) is threaded through blood vessels from a distant site to the brain, and a radiopaque substance (a substance that is impenetrable to x-rays) is injected through it. The role of angiography in glioma is usually limited to planning surgical removal of a tumor suspected of having a large blood supply.
Radionuclide brain scintigraphy uses a radioactive substance that is administered and absorbed by capillaries in the tumor, which are then viewed using imaging techniques.
Digital holography, a new technique that provides full three-dimensional mapping, is under investigation.

Lumbar Puncture (Spinal Tap)

A lumbar puncture is used to obtain a sample of spinal fluid, which is examined for the presence of tumor cells. A CT scan or MRI should generally be performed before a lumbar procedure to be sure that the procedure will be safe.

Biopsy

A biopsy is a surgical procedure in which a small sample of tissue is taken from the suspected tumor and examined under a microscope for malignancy. The results of the biopsy also provide information on the cancer cell type.

In some cases, such as brain stem gliomas, a biopsy might be too hazardous because removing any healthy tissue from this area can effect vital functions. In such cases, diagnosis must rely on less invasive and possibly less accurate measures. Of promise is the stereotactic technique (also called stereotaxy), which uses computers to provide three-dimensional views of very small areas. This may allow precise biopsies of cancer cells without affecting healthy brain tissue. Expertise in this technique is extremely important, however, and the technique is not widely available. [For a description of the stereotactic technique, see Surgery under What are the Treatments for Brain Tumors? , below. ]

Determining a Prognosis

The survival rates in people with brain tumors depend on many different variables:

Whether the tumor is malignant or benign.
Cancer cell type and location. (Location affects whether the tumor can be removed surgically or not.) [For description of specific tumors by cell type and location, see table Common Brain Tumors.]
Tumor grade. (This is the tendency to spread and the growth rate.) [ See Grading Tumors below.]
Patient's age. (The outlook is poorer in the very youngest and very oldest patients, although younger patients who survive two years after diagnosis have a much better outlook than older patients.)
Patient's ability to function.
Duration of symptoms.

Grading Tumors. Malignant primary brain tumors are classified according to tumor grade. Grade I is the least malignant and Grades IV and V are the most dangerous. Grading a tumor attempts to predict its tendency to spread and its growth rate. It is based on the appearance of the tumor cells as seen under a microscope.

Lower-grade (I and II) tumor cells are well defined and almost normal-shaped. (Some primary low-grade brain tumors are curable by surgery alone, and some are curable by surgery and radiotherapy. Low-grade tumors tend to have the most favorably survival rates and high-grade the least. However, this is not always the case. For example, some low-grade II gliomas are at very high risk for progression.)
Higher-grade (III and IV) tumor cells are abnormally shaped and more diffuse, which indicates more aggressive behavior. (High-grade brain tumors usually require surgery, radiotherapy, chemotherapy, and possibly investigational treatments.)
In tumors that contain a mixture of different-grade cells, the tumor is graded using the highest-grade cells in the mixture, even when there are very few of them. [ See also Table below.]

Molecular Markers. Elevated levels of certain cancer-associated molecules may be correlated with poor or positive prognosis in patients with specific types of brain cancer cells. Such markers include genetically mutated p53 and PTEN proteins and elevated levels of epidermal growth factor receptor (EGFR).

Genetic Profiles of Cancer Cells. Analyses that identify genetic types may soon help clinicians determine if patients with specific brain tumor cells might response to one treatment more than another. For example, specific genetic profiles of oligodendrogliomas have been associated with predictable responses to certain agents called nitrosourea alkylating agents (especially carmustine).

WHAT ARE THE GENERAL GUIDELINES FOR TREATING BRAIN TUMORS?

Treatment Options

The approach for treating brain tumors is to reduce the tumor as much as possible using surgery, radiation treatment (also called radiotherapy), chemotherapy, or investigative procedures. Such treatments are used alone or, more commonly, in combinations. With some very slow-growing cancers, such as those that occur in the midbrain or optic nerve pathway, patients may be closely observed and not treated until the tumor shows signs of growth. The intensity, combination, and sequence of these treatments depends on the glioma subtype, its size and location, and patient age, health status, and medical history.

Recent advances in surgical and radiation treatments have significantly extended average survival times compared to those of standard therapy. Investigative treatments, such as monoclonal antibodies, are also showing promise. Patients or their caretakers should discuss all options thoroughly with a specialist in brain cancer. Different specialists may be needed to help manage symptoms.

Specific Approaches for Children

Although the three options (surgery, radiation, and chemotherapy) are available for both adults and children, the approach for children differs from adults. Generally, in children with common brain tumors, therapy consisting of surgery, radiation, and a "tried and true" combination of the drugs vincristine, CCNU, and prednisone still yields the best chances of survival. In children under six, however, physicians try to use chemotherapy alone, if possible, and avoid radiation to prevent harm to the developing brain.

Emotional Support

Because of the low-curability rates of most malignant brain tumors, support for the patients and their families is a critical component of treatment and management. In response to one survey of patients with gliomas, experts made a number of recommendations to help both patients and caregivers:

Any physical impairment that could benefit from home equipment or physical therapy should be identified and treated.
Patients should discuss emotional as well as physical issues with their physicians. Depression, for instance, can be medically treated.
Relaxation techniques, meditation, and spiritual resources can be extremely helpful. Support groups are beneficial, but experts recommend separate groups for patients and their families.

A 1999 study gave some comfort by reporting that children with cancer have no more emotional or social problems than their healthy peers. In fact, teachers and students reported that, on average, such children tended to be less aggressive and more likable than their peers. It is more likely that the parents and caregivers suffer more emotionally. Caregivers themselves must seek help for the inevitable stress, depression, and tension arising from their difficult role.

WHAT ARE THE SURGICAL TREATMENTS FOR BRAIN TUMORS?

Surgery is usually the first step in treating most brain tumors, although in some cases, such as most brain stem gliomas, it may be too dangerous. The object of most brain tumor surgeries is to remove or reduce as much of its bulk as possible. By reducing the size, other therapies, particularly radiotherapy, can be more effective. (Some experts argue that in high-grade gliomas such extensive surgery may not improve survival rates at all and patients are best served by radiation therapy.)

Craniotomy

The standard procedure is called craniotomy:

The neurosurgeon removes a piece of skull bone to expose the area of brain over the tumor.
The tumor is located and then removed.

The surgeon has various surgical options for breaking down and removing the tumor. They include:

Standard surgical procedures.
Laser microsurgery (which produces great heat and vaporizes tumor cells).
Ultrasonic aspiration (which uses ultrasound to break the glioma tumor into small pieces, which are then suctioned out).

Relatively benign, grade I gliomas may be treated only by surgery. Some controversy exists over whether surgery for low-grade astrocytomas improves survival, although insufficient research has been conducted to prove its benefits or lack of them for these gliomas. Most malignant tumors require additional treatments, including repeat surgery.

The surgeon's skill in removing the tumor as completely as possible is critical to survival. No one should be shy about requesting the number of similar procedures a surgeon has performed. (Asking for complication rates may not be useful, since a very experienced surgeon might operate on many high-risk patients.)

Additional Procedures to Enhance Brain Surgery

In most cancers outside the brain, surgical removal of a tumor usually involves taking out surrounding healthy tissue to be sure all cancer cells are gone. In the brain, however, removing healthy nearby nerve tissue can be as disastrous for the patient as the cancer itself. Special techniques have been developed to allow maximum removal of tumor while protecting healthy brain cells.

Stereotaxy. Stereotaxy has become a useful adjunct to both surgery (stereotactic surgery) and radiotherapy (stereotactic radiotherapy). [ See Stereotactic Radiosurgery under How Is Radiotherapy Used in the Treatment of Brain Tumors?]

Cortical Localization. Cortical localization, or stimulation, uses a probe that passes a tiny electrical current to delicately stimulate a specific area of the brain. This produces a visible response of the body part (such as a twitch in a leg), which the stimulated region of the brain controls. The surgeon then knows to avoid those areas during the operation.

Image-Guided Surgery. Image guided surgery uses a three-dimensional picture of the patients' brain derived from computed tomography (CT) or magnetic resonance imaging (MRI) scans. The image, with various views of the brain, is displayed on a monitor in the operating room. During surgery, as the surgeon's instrument touches a part of the brain, a camera sends the image to a computer, which calculates the position of the surgical tool and displays it in its proper location on the 3-D image. The surgeon then can look at the monitor and see what structures to avoid.

Magnetic-Tipped Catheters. Neurosurgeons are investigating the use of a technique in which external magnetic fields direct a magnet-tipped flexible catheter to the tumor site through a path that avoids areas of the brain that could cause harm.

HOW IS RADIOTHERAPY USED FOR TREATING BRAIN TUMORS?

Role of Radiotherapy in Brain Tumors

Radiotherapy plays a central role in the treatment of most brain tumors, whether benign or malignant.

Radiotherapy after Surgery. Even when it appears that the entire tumor has been surgically removed, microscopic cancer cells often remain in the surrounding brain tissue. Radiation targets the residual tumor with the goal of reducing its size or stopping its progression. If the entire tumor cannot be removed safely, postoperative radiotherapy is often recommended. Even some benign gliomas may require radiation, since they may be life-threatening if their growth is not controlled.

Radiotherapy when Surgery Is not Appropriate. Radiotherapy may be used instead of surgery for inaccessible tumors or for tumors that have properties that are particularly responsive to radiotherapy.

Radiotherapy and Chemotherapy. Combining chemotherapy with radiotherapy is beneficial in some patients with high-grade tumors. In one study of children with medulloblastomas, reduced-dose radiation along with chemotherapy before and after this treatment was effective and resulted in a nearly 80% survival rate at five years.

Specific Radiation Treatments

Various radiation treatments are now available.

Conventional radiotherapy uses external beams aimed directly at the tumor and is usually recommended for large or infiltrating tumors. It begins about a week after surgery and continues five days per week for six weeks.

For tumors that are highly localized, the radiation therapist has a choice of other radiation treatments:

• Brachytherapy (also called interstitial radiation) uses radioactive "seeds" implanted directly in the tumor site. It is used as a booster to external beam radiation for patients with malignant astrocytoma. Brachytherapy appears to prolong survival in some aggressive gliomas. It may also be a safe and effective treatment for some children.

Conformal radiation uses high-dose radiation beams shaped to match the shape of the glioma. This technique is highly targeted and, in certain cases, may even be used for patients who have had previous radiotherapy.
Hyperfractionated radiation uses many small radiation doses to deliver a high total dosage of radiation.
A balloon catheter that delivers radiation to the tumor cavity after surgery is showing promise.

Stereotactic Radiosurgery

Stereotactic radiosurgery has been developed to allow highly targeted radiation to be delivered directly to the small tumors while avoiding healthy brain tissue. The term radiosurgery is used because the destruction is so precise that it acts almost like a surgical knife. Some studies are finding that stereotactic radiosurgery improves survival, even in patients with the highly aggressive glioblastoma multiforme brain cancer. The procedure is being tested to boost standard radiotherapy.

Benefits of Stereotaxy. There are a number of benefits for stereotaxy:

Stereotaxy allows precisely focused, high dose beams to be delivered to gliomas less than 1.25 inch in diameter.
Investigators have found that stereotactic radiosurgery can help them reach small tumors located deep in the brain that were previously considered inoperable.
Sometimes with stereotaxy only a single treatment may be needed.
Unlike traditional radiotherapy, stereotactic radiotherapy can be repeated, so it is useful for recurrent tumors when a patient has already received standard radiation treatments.
Combining stereotaxy with techniques that gauge speech and other mental functions in patients who are awake during the procedure can allow removal of brain tissue with a lower risk for complications in areas that affect such functioning.

The Planning Procedure. Stereotactic radiosurgery usually begins with a series of steps designed to plan the radiation target:

First, the patient is given a local anesthetic. The patient's head must be totally immobilized by screwing a device known as a stereotactic frame into the patient's skull. (The frame procedure is effective only on brain tumors that have regular margins.) The frame is removed as soon as the whole procedure has been completed (about three to four hours.)
A three-dimensional map, usually using magnetic resonance imaging scans (MRI), is made of the patient's brain.
A computer program calculates dosage levels and specific areas for radiation targeting.

So-called frameless stereotaxy has been developed to eliminate the frame and may be effective on more tumors. One frameless technique uses computing techniques based on cruise-missile technology to calculate the slightest variations in movements of the head and the location of the tumor relative to these movements. These calculations are then used to target the radiation beams directly on the tumor, even if the patient's head is moving slightly.

Delivery of Radiation Beams. Once the preliminary planning stage has been completed, treatment begins. A number of advanced machines, such as the Gamma Knife , adapted linear accelerator (LINAC) , and cyclotron, are being used with stereotaxy and can deliver very focused beams of radiation. Actual treatment takes 10 minutes to an hour.

The gamma knife uses gamma rays that are sent from multiple points to converge at a single point on the tumor. Although each gamma-ray beam is very low dosage, when the beams converge, the intensity and destructive power is very high. The gamma knife is limited to very small tumors and so is generally useful as booster after standard radiation, surgery, chemotherapy, or combinations.
The linear accelerator (LINAC) produces photons (positively-charged atomic particles) in patterns that are matched to the tumor shape. The patient is positioned on a bed that can be moved to allow flexible positioning. It allows treatment over multiple sessions of small doses (fractionated sterotactic radiotherapy), instead of a single session. This means that larger tumors can be treated.
The cyclotron is basically an atom smasher, which produces protons that can be directed toward the tumor. As part of this procedure, some researchers are using boron neutron capture therapy (BNCT). BNCT employs intravenous administration of a boron compound, which is picked up more selectively by tumor cells than by normal brain tissue. The cyclotron delivers a single dose of radiation which triggers the release of high-energy particles from the boron that destroy nearby tumor cells. The cyclotron is available only in a very few locations.

Drugs Used With Radiation

A number of drugs may be used along with radiation that may increase the effectiveness of the treatment:

Radioprotectors. They protect healthy cells during radiation
Radiosensitizers. These agents make cancerous cells more sensitive to radiation. For example, combinations of the radiosensitive drugs iododeoxyuridine, 5-FU, RSR 13, and hydroxyurea are promising. Such treatments usually require aggressive use of other, protective agents to prevent severe side effects.
Radioenhancers. These drugs, such as topotecan, increase the effects of radiation.

Side Effects of Radiation

Common Side Effects. Side effects of radiotherapy include hair loss, nausea and vomiting, and fatigue. In some cases, it may worsen some existing symptoms of brain tumors, seizures, difficulty in swallowing, and movement problems. Fluid build-up (edema) may occur. Such side effects are usually temporary and treatable with steroids. It is sometimes difficult to tell symptoms of the disease from those of the treatments.

Tissue Injury. Radiation necrosis (total destruction of nearby healthy tissue) occurs in about 25% of patients treated with radiation. This condition is highly associated with reduction in mental functions. In nearly half the cases of standard radiation therapy, additional surgeries are needed on areas injured by radiation. Other treatments that are showing promise for treating necrotic tissue include administration of oxygen and pentoxifylline (an agent that improves blood flow).

Specific Issues in Small Children. In small children, radiation therapy can impair growth and learning. Growth hormone is often used after radiotherapy and is effective in restoring growth in many of these children. Although there has been some concern that growth hormone may increase the risk of relapse, a 2000 study reported that, in fact, these children had a lower rate of recurrence than those who did not take growth hormone.

HOW IS CHEMOTHERAPY USED IN TREATING BRAIN TUMORS?

Chemotherapy involves the use of toxic drugs to kill cancer cells. They may be given orally, intravenously, or administered directly into the central nervous system. Chemotherapy is not an effective initial treatment for low-grade brain tumors, mostly because standard drugs cannot pass through the blood brain barrier. Recently, however, researchers have identified certain genetic arrangements in specific brain tumors that make them sensitive to the effects of chemotherapy. In general, however, chemotherapy is usually administered in brain cancer as salvage therapy for recurrent or slowly progressing cancers in patients who have previously been treated.

Drugs Used in Chemotherapy

Carmustine (also called BCNU). Carmustine is known as a nitrosourea alkylating agent. The response of gliomas to these agents appears to depend upon certain genetic factors. About 70% of gliomas have an enzyme (MGMT) that protects against their actions. The other 30%, however, are sensitive to it. As this time, it is commonly used for glioblastoma multiforme and to date, no agent has proved to be superior for these tumors.

PCV. The drug regimen called PCV (procarbazine, lomustine, and vincristine) is effective treatment for many common brain tumors. (CCNU is more commonly referred to as lomustine.) PCV has significant benefits against a subset of patients with oligodendroglioma. It has produced improvements in patients with anaplastic astrocytoma and glioblastoma multiforme, but to date does not appear to be any more effective than carmustine for these tumors. This regimen has significant toxicity and patients must adhere to certain dietary restrictions.

Each of these drugs is also used separately and in other combinations. Examples include the following:

Procarbazine is a particularly effective agent. Procarbazine is commonly used for recurring tumors. Adding tamoxifen may provide modest benefits for patients with recurring high-grade gliomas.
Carboplatin with or without vincristine is being studied for low-grade progressive gliomas, which are difficult to treat with surgery or radiation.

Temozolomide. Temozolomide (Temodal) is the first drug to be approved for brain tumors in 20 years. This oral agent improves both survival and quality of life for many patients with brain tumors. It has been specifically indicated for adult patients with anaplastic astrocytoma that does not respond to other treatments. It is showing promise for recurrent high-grade gliomas, in anaplastic oligodendrogliomas, and in low-grade astrocytomas. Studies have suggested that it may be more effective for certain tumors than procarbazine.

Other Chemotherapy Agents Used for Recurring or High-Grade Cancers

A number of drugs and treatments are being tested or used for primary and recurring tumors.

Tamoxifen, a breast-cancer drug, may also be beneficial in some patients with glioma, particularly in making standard drugs more effective. More research is needed.
Temozolomide may improve survival in patients with recurrent anaplastic astrocytoma and possibly even glioblastoma multiforme.
High-dose thiotepa along with bone marrow or stem cell transplantation is being tested for newly diagnosed aggressive oligodendroglioma as an alternative to radiotherapy. Although some patients have prolonged disease-free survival time, thiotepa has very toxic side effects, including encephalopathy (brain damage), liver damage, severe weight loss, and a drop in blood platelet count. High-dose thiotepa along with bone marrow or stem cell transplantation is being investigated for recurrent aggressive oligodendroglioma. [ See Transplantation Procedures , below. ]
Paclitaxel (Taxol), a drug used for breast cancer, is also being investigated for gliomas. It is showing promise for patients with recurrent gliomas. In one study, paclitaxel with stereotactic radiosurgery improved results for patients with glioblastoma multiforme.
Topo I inhibitors, a new class of anti-tumor drugs, are being studied for blocking topoisomerase I (Topo I), an enzyme involved in cell replication. Clinical studies have shown that the Topo I inhibitors topotecan or Irinotecan injure brain tumor cells. Combinations of Topo I inhibitors with standard chemotherapy drugs may prove to be very effective. In one 2001 study, topotecan also was effective in enhancing radiation treatments.
5-fluorouracil (5-FU). 5-fluorouracil (5-FU) is a standard chemotherapy agent for a number of malignancies. It has not, to date, been useful for brain tumors, because like most of these agents, it cannot pass the blood brain barrier. A new form (Ethypharm) now employs a microsphere containing the drug that is implanted in the tissue. Early studies are promising.

Side Effects of Chemotherapy

Because chemotherapeutic drugs may also affect normal cells, side effects are common. To help offset these effects, chemotherapy is given intermittently over a scheduled period that allows normal cells to recover between treatments. Side effects include nausea, vomiting, fatigue, infection, bleeding, and hair loss. In addition, the agents used to treat symptoms (anti-seizure drugs, antidepressants, and corticosteroids) may interfere with standard chemotherapeutic agents. Specific drugs may have different complications; for example, vincristine can cause nerve injury and cisplatin may result in hearing loss. Procarbazine requires dietary restrictions. Side effects are almost always temporary and may be managed with other medications.

Enhancing Drug Access to the Tumor

To make chemotherapy more effective, scientists are working on a number of approaches to overcome an obstacle unique to brain cancer: the blood-brain barrier, a functional barrier that protects the brain and prevents certain molecules from passing through.

Certain drugs, such as mannitol or agents called receptor-mediated permeabilizers, may open the barrier without worsening neurological deficits.
A technique called interstitial chemotherapy may improve delivery of chemotherapeutic agents. The physician places disc-shaped wafers (known as Gliadel wafers) soaked with a chemotherapeutic drug directly into the surgical cavity after a tumor is removed. In one early study, six-month survival rates after the procedure were about 60%. The procedure does not appear to increase the risks of side effects over those of the surgery itself.
Intrathecal infusion delivers chemotherapeutic drugs directly into the spinal fluid.
Intraarterial delivery administers high-dose chemotherapy into arteries in the brain using tiny catheters. In a 2000 study, this approach was used within two weeks of radiotherapy in patients with high-grade astrocytomas, and the survival rates for glioblastoma multiforme tripled (20 months) compared to those who had chemotherapy and radiation at the same time.
Enclosing highly potent anti-cancer drugs, such as anthracyclines, in protective microspheres (called liposomes) may allow the drugs time to enter tumors without unduly increasing the risk for severe toxicity. Such agents are not ordinarily used for brain cancers because of high toxicity and poor penetration of brain tumors.
An investigative technique called electrochemotherapy (ECT) applies high-voltage pulses to deliver drugs across cancerous tissues, including those of the brain.

WHAT ARE SOME INVESTIGATIVE THERAPIES USED FOR BRAIN TUMORS?

A number of drugs that target specific mechanisms associated with brain cancer are being tested. Combinations of some of these drugs with or without standard chemotherapy and radiotherapy may prove to be more effective than the use of any one treatment. It should be noted that none of these drugs at this time are producing cures, although some are improving survival.

Immunotherapy

Immunotherapy aims at using modalities that boost the patient's own immune system's ability to seek out and destroy cancerous cells.

Monoclonal Antibodies. Monoclonal antibodies (MAbs) are genetically engineered antibodies designed to work against a specific target. In one particularly promising approach, MAbs are bound with radioactive iodine and delivered directly into the brain and sometimes into the tumor. The MAbs are specifically designed to lock with the surface of certain cells in the tumor. Once they do so, the radioactive iodine destroys the cell. The approach is essentially mini-radiation therapy without the damage or severe side effects of standard radiation treatments. Some experts believe this could prove to be the most effective therapy against high-grade gliomas. In one study, the treatment extended average survival time to 23 months in these patients (which is normally 11 months).

Interleukin and Interferon. Interleukin and interferon, natural proteins created by the immune system that are toxic to many tumor cells, are under investigation. A promising treatment called IL-4 toxin therapy combines interleukin-4 with Pseudomonas exotoxin, a powerful cancer cell killer that comes from a bacterium. The combination is delivered directly to the tumor and in animal studies has caused tumor regression. Some, but not all, studies have found improved survival rates when interferon was added to a regimen of chemotherapy.

T-Lymphocytes. T-lymphocytes, or T-cells, are white blood cells that fight foreign invaders. A subgroup called killer T-cells are grown in the laboratory and are injected directly into the tumor to boost an immune response. In one very small study of five patients, specially modified killer T-cells were implanted after surgery in the tumor area and patients were given infusions of the agent over a one to two week period. After about 30 months, two patients had no evidence of tumor recurrence, one patient was stable, and two died.

Tumor Vaccines. Tumor vaccines are also being created, in which tumor cells are removed from the patient and inactivated; when they are transferred back to the patient, they are harmless but can elicit a powerful immunologic response against the tumor. For example, a vaccine that combines tumor proteins with the patient's nerve cells is being tested in astrocytomas.

Gene Therapy

Gene therapy involves the transfer of genetic material into a tumor cell to destroy the cell or to stop its growth. Many genes are under investigation:

Genes that signal tumor cells to self-destruct.
Genes that make cells more mature, which slows cell growth.
Genes that can strengthen the immune system's attack on the tumor.
Genes that increase the cell's responsiveness to certain drugs.

To date, results of human trials have been disappointing, although approaches that deliver genetic material by using inactivated adenoviruses are showing some promise.

Angiogenesis Inhibitors

Angiogenesis inhibitors are drugs that interfere with the growth of blood vessels in the tumor, effectively starving tumors of vital nutrients and oxygen. Treatment using these drugs is often called angiostatic therapy. They include the following:

Thalidomide was one of the first drugs being tested, but results were disappointing.
In a 2001 study suramin, another angiostatic agent, produced a delayed response in some patients with high-grade gliomas and was well tolerated. Anti-seizure medication did not effect it. It is now being studied in combination with radiation therapy.

Others under investigation include angiostatin, endostatin, TNP-470 (a derivative of a fungal antibiotic), platelet factor 4 (PF4), contortrostatin (found in copperhead venom), and squalamine (a substance found in shark's liver). (It should be noted that shark cartilage itself appears to have no effect against cancer.)

Other Investigative Agents

Retinoids. Retinoids are vitamin A derivatives and act as differentiating agents in cancer treatments. That is, they can convert immature, dividing tumor cells into mature cells, stopping tumor growth. In one study, retinoic acid appeared to have modest clinical activity against recurrent malignant gliomas with tolerable side effects. Other studies indicate that retinoic acid has no significant effect as a single agent, but combinations with radiotherapy and other drugs may hold promise. For example, one study reported some success in treating high-grade malignant gliomas with radiotherapy and concurrent use of interferon and retinoic acid. Another showed promise against recurrent gliomas using combinations of retinoic acid and arabinoside, a chemotherapeutic drug.

Toxins. Agents are being developed that use toxins to kill malignant brain cells.

One promising agent employs diphtheria (TransMID-107R). This drug is now in late clinical trials for recurring cancer but is also being investigated for newly diagnosed and metastatic brain cancers.
A mushroom toxin (irofulven) is a potent cancer-cell killer and is in second-phase clinical trials

Imatinib (Gleevac). Imatinib inhibits an enzyme called Bcr-Abl kinase, which is produced by certain leukemia cancer cells and has been approved for these leukemias. Although Gleevac is an unproven treatment for brain tumor, early trials on recurrent malignant glioma are under way.

Marimastat. Marimastat is a unique drug that inhibits the enzyme metalloproteinase, which may play a role in brain cancer. The drug is being used in patients with glioblastoma multiforme who have completed treatment with surgery and radiotherapy. It has not proven to prolong survival to date, however.

Taurolidine. Taurolidine is a unique agent that prevents tumor formation and growth in animals. An early clinical trial in patients with high-grade gliomas is under way.

Other Drug Targets. Another development is the discovery of a protein called BEHAB (Brain-Enriched Hyaluronan Binding Protein). BEHAB is produced only by invasive glioma tumor cells, not by normal brain tissue or noninvasive tumor cells. Breakdown of BEHAB releases a substance called hyaluronan-binding domain (HABD) that appears to give glioma cells the ability to invade other areas of the brain. Both BEHAB and HABD represent potential targets for new therapies.

Transplantation Procedures and High-Dose Chemotherapy

Chemotherapy destroys not only cancer cells, but also healthy cells, including special blood cells in the bone marrow called stem cells, which are immature cells from which all blood cells develop. Transplantation procedures using bone marrow or stem cells allow high-dose chemotherapy to be administered while protecting blood cells. The procedures are being tested for patients with brain tumors that are responsive to the effects of chemotherapy.

Photodynamic Therapy

Photodynamic therapy employs a special agent (Photofrin) that is absorbed by the tumor and causes the cancer cells to become fluorescent when a laser is directed at them. It is being investigated in late-stage trials in combination with other treatments.

WHAT ARE TREATMENTS FOR SOME COMPLICATIONS OF BRAIN TUMORS?

Hydrocephalus

Some tumors, particularly medulloblastomas, interfere with the flow of cerebrospinal fluid and cause hydrocephalus. This causes a build-up fluid in the ventricles (the cavities) in the brain. This can cause nausea and vomiting, severe headaches, lethargy, difficulty staying awake, seizures, visual impairment, irritability, and tiredness.

Corticosteroids (commonly called steroids), such as dexamethasone (Decadron), prednisolone, and prednisone are used to treat hydrocephalus (fluid build up in the brain). Side effects include high blood pressure, mood swings, susceptibility to infection, increased appetite, facial swelling, and fluid retention.

Human corticotropin-releasing factor (hCRF), a naturally occurring neurohormone, appears to possess substantial anti-swelling properties and thus has been proposed as an alternative to corticosteroids in brain edema, with potentially fewer side effects.

A shunt procedure may be performed to drain fluid. Shunts are flexible tubes used to reroute and drain the fluid.

Seizures

Seizures are common in brain tumor cases, with younger patients having higher risks than older ones. Anti-epileptic medications, such as carbamazepine or phenobarbital, may used to treat seizures and are helpful in preventing recurrence. These agents are not useful in preventing a first seizure, however. It should also be noted that anti-seizure medications might interact with some of the chemotherapies used to treat the brain cancers, including paclitaxel, interferon, and retinoic acid. Patients should discuss these interactions with their physician. [For more information see the Report # 44, Epilepsy.]

Depression

Antidepressants are very useful for treating the emotional side effects of this disease. Support groups can also have great benefit for both patients and families. [ See Where Else Can Help be Found for Brain Tumors?]

WHERE ELSE CAN HELP BE OBTAINED FOR BRAIN TUMORS?

American Brain Tumor Association, 2720 River Road, Des Plaines, IL 60018-4110. Call (800-886-2282) or (847-827-9910) or on the Internet (http://www.abta.org/). This is an excellent organization that provides good information and resources.

The Brain Tumor Society, 124 Watertown Street, Suite 3-H Watertown, MA 02472 Call (800-770-8287) or on the Internet (http://www.tbts.org)

Musella Foundation For Brain Tumors, Research & Information, 1100 Peninsula Blvd., Hewlett, NY 11557. On the Internet (http://www.virtualtrials.com)

Children's Brain Tumor Foundation, 274 Madison Avenue, Suite 1301, New York, NY 10016. Call (212-448-9494) or on the Internet (http://www.childrensneuronet.org)

National Brain Tumor Foundation, 785 Market Street, Suite 1600, San Francisco, CA 94103. Call (800-934-CURE) or on the Internet (http://www.braintumor.org)

American Association of Neurologic Surgeons, 550 Meadowbrook Drive, Rolling Meadows, Illinois 60008-3845. Call (847-378-0500) or (888-566-AANS (2267) or (http://www.neurosurgery.org/)

American Cancer Society, 1599 Clifton Road, NE, Atlanta, GA 30329. Call (800-ACS-2345) or (404-320-3333) or on the Internet (http://www.cancer.org)

National Cancer Institute.
The NCI has help line open during working hours (call 800-4-CANCER) or (800-422-6237) or on the Internet (http://cis.nci.nih.gov/). The NCI offers free information on all aspects of cancer. The following site lists clinical trials (http://cis.nci.nih.gov/resources/clinical.html)

National Coalition of Cancer Survivors. Call (Phone: (877) NCCS YES (877-622-7937) or on the Internet (http://www.cansearch.org/)

Oncolink from the University of Pennsylvania provides excellent links and in-depth free can information (http://cancer.med.upenn.edu/disease/). 1010 Wayne Avenue Suite 770 Silver Spring, MD 20910-5600

Pediatric Oncology Group, 645 N. Michigan Ave., Suite 910, Chicago, IL 60611. Call (312) 482-9944 (http://www.pog.ufl.edu/) The International Radiosurgery support association

(http://www.braintumor.org/pservices/csbtstereotatic.asp)

On the Internet:

National Association of Physicians for the Environment (http://www.napenet.org)

University of Pennsylvania sponsors an excellent cancer site

at (http://oncolink.upenn.edu/disease/melanoma/)

National Comprehensive Cancer Network (http://www.nccn.org)

American Society for Clinical Oncology (http://www.asco.org/)

Anatomy of the Brain or (http://www.waiting.com/brainanatomy.html)

For family members of patients with neurologic problems (http://www.waiting.com/)

FIND A NEUROLOGIST

http://www.aan.com/rostersearch_f.html 1080 Montreal Avenue, St. Paul, Minnesota 55116

FIND A NEUROSURGEON

http://www.neurosurgery.org/health/findaneurosurgeon.html (also includes neurosurgeons worldwide)

http://www.tbts.org/resorgwl.htm (Brain Cancer Resources)

http://www.virtualtrials.com/

http://cancernet.nci.nih.gov/