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In This Report

•	Highlights
•	Introduction
•	Symptoms
•	Risk Factors
•	Causes
•	Prognosis
•	Diagnosis
•	Common Brain Tumors
•	Treatment
•	Surgery
•	Radiotherapy
•	Chemotherapy
•	Other Treatments
•	Treatment for Complications...
•	Resources
•	References

Encyclopedia

•	Acoustic neuroma
•	Posterior fossa tumor
•	Brain tumor - children

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Brain Tumors: Primary

Highlights

Temozolomide (Temodar) for Glioblastoma

• In 2005, the FDA approved temozolomide for treating glioblastoma multiforme. Temozolomide was previously approved only for anaplastic astrocytoma. A 2005 study found that patients with glioblastoma who received temozolomide and radiation had better survival outcomes than patients who received only radiation. Temozolomide is taken by mouth and has relatively few side effects.

Chemotherapy for Medulloblastoma

• Medulloblastoma, the most common form of childhood brain tumor, is usually treated with surgery and radiation therapy. However, radiation therapy has severe side effects. A 2005 landmark study investigated a combination chemotherapy regimen instead of radiation for very young children (under 3 years). Most children with non-metastasized medulloblastoma had an excellent outcome and were able to avoid radiation.

Brain Tumor Care and Recommended Guidelines

Patients with brain tumors do not always receive the care recommended by national guidelines, according to a 2005 Journal of the American Medical Association study. The study evaluated nearly 800 patients with grade III or grade IV glioma who were treated at academic and community hospitals. Researchers discovered:

• Nearly 90% of patients were treated with antiepileptic drugs, although only 32% of the patients had seizures. These drugs do not prevent first seizures and guidelines recommend against giving them to patients with newly diagnosed brain tumors.
• Only 8% of patients received antidepressant medication even though over 90% reported depressive symptoms.
• Only 7% of patients received the blood-thinning drug heparin at the time of surgery. Blood clots can occur in many patients who have brain tumor surgery.
• Only 15% of patients participated in clinical trials, although most patients were treated at academic medical centers.
• Only half of patients received chemotherapy in addition to radiation and surgery.
• As recommended, most patients did receive an MRI at diagnosis, surgical resection, and radiation following surgery.

Introduction

Brain tumors are composed of cells that exhibit unrestrained growth in the brain.

The major areas of the brain have one or more specific functions.

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 otherwise specified.)

Benign Tumors

Benign tumors represent half of all primary brain tumors. Their cells look relatively 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.

Click the icon to see an image of a primary brain tumor.

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.

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. Normal astrocytes provide nutrients, support, and insulation for nerve cells and are one of the primary neurologic cells in the body. The malignant astrocytomas called glioblastomas account for 23% of brain tumors and are the most common ones.
• Oligodendrogliomas develop from oligodendrocyte glial cells, which form the protective coatings around nerve cells. Although oligodendrogliomas 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.
• Ependymomas are derived from ependymal cells, which 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 primary tumors in the central nervous system. About 30% of these tumors occur in the spinal cord.
• Mixed Gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

It should be noted that gliomas may also contain cancer cells derived from brain cells other than glial cells.

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.

Meningiomas. Meningiomas are usually benign tumors that develop in the membranes that cover the brain and spinal cord (the meninges).

Click the icon to see an image of 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 hemangiopericytomas are less common and are difficult to remove surgically.

Cerebral Astrocytomas. Gliomas that develop inside the brain often occur in the cerebral hemispheres (the right and left sides of the brain). In such cases, they are referred to as cerebral astrocytomas. Gliomas sometimes occur in another part of the brain called the cerebellum, which is responsible for balance and coordination. In such cases, the term cerebellar astrocytoma is used.

Click the icon to see an image of the function of the left cerebral hemisphere.

Click the icon to see an image of the function of the right cerebral hemisphere.

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.

Click the icon to see an image of the function of the brainstem.

The brain stem consists of three primary parts.

• The medulla regulates breathing, swallowing, blood pressure, and heart rate.
• The pons links the cerebellum to the cerebrum.
• The midbrain helps control vision and hearing.

Click the icon to see an image of the structures of the brain.

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.

Click the icon to see an image of the function of the cerebellum.

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

Click the icon to see an image of 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.

Click the icon to see an image of the optic nerve.

Symptoms

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 everyone has headache, and they rarely represent an underlying brain tumor. Headaches caused by brain tumors may vary depending on the location, and many different 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 (such as vomiting or 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 - 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
• Increased sleep

Other Significant Symptoms

• 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

They symptoms below indicate an emergency condition and require immediate medical attention.

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

Risk Factors

Nearly 360,000 people in the US are currently living with brain cancer. Men are at higher risk for most brain tumors than women. Primary malignant brain tumors are still uncommon and represent only 1.3% of all cancers diagnosed in the United States and 2.4% of all deaths due to cancer.

Primary brain cancers are rare, occurring 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. The increase, however, is most likely due to the rise in incidence of non-Hodgkin's lymphomas--which can occur in the brain. When this malignancy is eliminated, any increase in other tumors is not significant.

Age

The average age of diagnosis for brain tumors is 57, and 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 3 and 12

Risk Factors in Children. Tumors in the central nervous system are now the most common primary cancers in children, but they are still rare. An estimated 3,110 benign or malignant brain tumors are expected to be diagnosed in children each year. 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:

• 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.)

Click the icon to see an illustrated series detailing colon cancer surgery.

Ethnicity

The risk for primary brain tumors in Caucasians is higher--as much as twofold depending on type--than in African Americans.

Environmental or Occupational Risk Factors

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

Studies on the effects of lower-energy radiation, such as microwaves and electromagnetic fields, have been uncertain. One study reported that men whose jobs exposed them to electromagnetic fields had higher rates for brain cancer, although a more recent study found a higher risk only in men who were also exposed to chemicals (petroleum, solvents, lead, pesticides and herbicides).

A 2002 study on Korean War veterans highly exposed to microwaves from radar equipment reported no excess risk for brain cancer--or any other malignancy--over a 40-year period. Studies in both 2000 and 2001 found no evidence to suggest a higher risk with cellular phones and other wireless devices that use radiofrequency.

Chemical and Metals in Brain Tumors. High exposure to a number of metals and chemicals have been associated with brain tumors, such as the following:

• High exposure to certain chemicals, including vinyl chloride and petroleum products, has been associated with brain tumors.
• High levels of lead, arsenic, or mercury exposure have been linked to a higher risk. One study suggested that lead exposure was particularly associated with meningiomas. It is unknown whether these associations are real, and confirmatory studies are needed.
• There has been some suggestion of a higher risk with exposure to pesticides.A major study of pesticides is underway, but results are not in yet. A 2003 study indicated that parental exposure to pesticides or herbicides did not appear to be important in increasing risk for brain cancer in their children.

Brain cancer is uncommon, and, over the course of their lifetime, many people are exposed to these chemicals, many of which are very common. To date, there has been no clear evidence that implicates any specific industrial chemical or metal.

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 disease (neurofibromatosis)
• Von Hippel Lindau disease
• Familial polyposis (Turcot's syndrome)
• Osler-Weber-Rendu syndrome

Organ Transplantation

A 2002 study reported a higher risk for brain cancers in patients who had undergone organ transplantations. Researchers believed that the drugs used to suppress the immune response after the procedures may increase the risk.

Medical Conditions Associated with a Lower Risk for Brain Tumors

A 2002 study reported lower risks for brain cancers in individuals with allergies and autoimmune diseases (such as type 1 diabetes). Autoimmune diseases were also associated with a lower risk for meningiomas. The cause of this possible association remains unknown.

Studies have also found an association between lower risk for gliomas and a history of infection with varicella zoster, the virus that causes chicken pox and shingles.

Click the icon to see an image of the chicken pox.

Causes

A number of defective genes are involved in the cancer process. Genes that cause cancer proliferation (called oncogenes) and those that normally suppress tumors but are defective (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 such 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.

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.

Prognosis

Currently estimated 13,100 people die from malignant brain tumors a year.Recent advances in surgical and radiation treatments have significantly extended average survival times and can reduce the size and progression of malignant gliomas. In general, survival rates are highest in younger people and lowest in the elderly.

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. 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.

Unfortunately, the majority of primary brain tumors, notably anaplastic astrocytomas and glioblastoma multiforme, are only rarely curable.

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 doctor.

Diagnosis

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 doctor 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.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI creates a three-dimensional picture of the brain, which allows doctors to more precisely locate problems such as tumors or aneuryms.

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.

Click the icon to see an image of a CT scan of the brain.

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. 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. PET is not routinely used for diagnosis, but it may supplement MRIs to help determine tumor grade after a diagnosis. Data from PET may also help improve the accuracy of newer radiosurgery techniques.

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.

Click the icon to see an image of a lumbar puncture.

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.

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)
• The tendency to spread and the growth rate (tumor grade)
• Patient's age
• Patient's ability to function
• Duration of symptoms

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.

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 are 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.

Biologic Markers. Elevated levels of certain cancer-associated molecules or compounds may be correlated with prognosis. For example, evidence of genetically mutated p53 indicates a poorer prognosis in younger patients with glioblastoma multiforme.

Elevations of epidermal growth factors (EGF) or vascular endothelial growth factors (VEGF) suggest aggressive tumors. High levels of the receptor for EGF (EGFR), in fact, are found in 70% of glioblastoma specimens.

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).

Common Brain Tumors

Treatment

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.

Emotional Support

Because of the low-cure 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 doctors. 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.

Lifestyle Measures

Although there is little evidence that dietary measures have any effect on brain cancer, some studies suggest the following might be helpful.

Dietary Restriction. Calorie restriction has been associated with cancer protection in some animal studies. One study reported brain tumor regression in mice that were put on a restrictive diet (calories are reduced but without causing nutritional deficiencies). Limiting calories appeared to help slow down tumor angiogenesis (blood vessel growth, which feeds the tumor). Not all animal studies support these results, however, and there are no human studies on this approach.

Soy. One study suggested that compounds in soy, such as genistein, suppresses invasiveness and growth of some cancers, including gliomas. It is not known whether this approach is beneficial to patients with brain tumors, however.

Surgery

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. (Although there have been significant advances in brain surgeries, some experts argue that in high-grade gliomas 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.

Click the icon to see an illustrated series detailing craniotomy surgery.

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 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).

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 patient's brain derived from computed tomography (CT) or magnetic resonance imaging (MRI) scans. An advanced technique called high-field interventional MR imaging (iMRI) is particularly accurate in identifying the tumor, but it is not widely available. 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.

Radiotherapy

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 (Radiochemotherapy). Combining chemotherapy with radiotherapy is beneficial in some patients with high-grade tumors.

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. It should be noted that older adults have a more limited response to external-beam radiation therapy than younger people.

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 three-dimensional 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 with some success 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 (GliaSite) 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. In the standard operation, 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.

Advanced imaging techniques are now allowing frameless stereotaxy, which eliminates the frame and may be effective on more tumors. For example, high-field interventional MR imaging (iMRI) uses a guidance system 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 1 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 stereotactic 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 that 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 and there have been few trials to date.

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, 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. Topotecan combined with other drugs, such as thiotepa and carboplatin, may help children with neuroblastoma and brain tumors. A 2002 study using topotecan for glioblastoma multiforme was disappointing, but different methods of administration or other similar drugs may be useful. Efaproxiral, an investigative agent that increases oxygen in the brain, is showing promise as a radioenhancer.

Side Effects of Radiation

Common Side Effects. Side effects of radiotherapy include hair loss, nausea and vomiting, and fatigue. In some cases, radiation 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. Patients often develop problems in thinking and concentration after radiation treatments. One study suggested that administering oxygen under pressure, called hyperbaric oxygen, may provide some small benefits. 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).

Secondary Tumors. Of concern is a study reporting a few cases of second tumors developing in the areas treated with radiosurgery. The incidence appears to be very low, but experts suggest continued surveillance may be appropriate.

Specific Issues in Radiation Therapy for Small Children. In small children, radiation therapy can impair growth and learning. Precise radiation techniques, such as three-dimensional conformal radiation therapy, may help some children while limiting the injury to healthy brain tissue. 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.

Chemotherapy

Chemotherapy involves the use of drugs to kill cancer cells. They may be given by mouth, injected into an IV, or injected 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. Of some promise, 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. The role of chemotherapy with brain cancers is constantly under investigation and there are some promising studies.

Drugs Used in Chemotherapy

Carmustine (also called BCNU). Carmustine is known as a nitrosourea. 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% are sensitive to it. At this time, it is commonly used for glioblastoma multiforme and to date, no agent has proved to be superior for these tumors. Unfortunately, most patients quickly develop resistance to the drug, so there have been few improvements in survival rates with its use.

PCV and its Agents. The drug regimen called PCV (procarbazine, CCNU, and vincristine) is effective treatment for many common brain tumors. (CCNU is also referred to as lomustine and, like carmustine above, is a nitrosourea.) PCV has significant benefits for about two-thirds of patients with oligodendrogliomas. 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, including suppression of red blood cell production and cause nausea, vomiting, and weight loss. Patients must adhere to certain dietary restrictions. Each of these drugs is also used separately and in other combinations.

Temozolomide (Temodar). Temozolomide, the first new drug approved for brain tumors in several decades, may improve quality of life and increase the time to progression for many patients with malignant gliomas. Temozolomide is taken by mouth and has relatively few side effects. In 1999, it was approved for adult patients with anaplastic astrocytoma that did not respond to other treatments. In 2005, it was approved for use during and after radiation therapy for patients newly diagnosed with glioblastoma multiforme. It is showing promise for recurrent high-grade gliomas, anaplastic oligodendrogliomas, and low-grade astrocytomas. It has only modest and short-lived effects on recurrent gliomas. Clinical trial results presented at the 2004 American Society of Clinical Oncology (ASCO) meeting confirm that temozolomide administered during and/or after radiation is a first-line treatment for glioblastoma multiforme. A 2005 study, published in the New England Journal of Medicine, reported that adults with newly diagnosed glioblastoma who received temozolomide during and after radiation therapy had a higher rate of 2-year survival than patients who received radiation alone.

Other Chemotherapy Agents Used or Investigated 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 a minority of patients with glioma when administered continuously at high doses. More research is needed to determine which patients may benefit.
• 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.
• 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 block topoisomerase I, an enzyme involved in cell replication. Clinical studies have shown that the Topo I inhibitors topotecan and irinotecan injure brain tumor cells. Combinations of Topo I inhibitors with standard chemotherapy drugs, such as BCNU, is proving to be effective for some patients. Some studies suggest it may help some children with gliomas. They may also be important agents in radiochemotherapy. Less positive studies on irinotecan report that combinations with anti-seizure medications reduce its effectiveness.
• 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), however, employs a microsphere containing the drug that is implanted in the tissue. Early studies are promising. Investigators are also looking at genetic therapies to deliver the drug directly to the tumor.
• Carboplatin with or without vincristine is being studied for low-grade progressive gliomas, which are difficult to treat with surgery or radiation.

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.

Approaches to Enhance 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.
• Interstitial chemotherapy uses disc-shaped wafers (known as Gliadel wafers) soaked with carmustine, the standard chemotherapeutic drug for brain cancer. The doctor places the wafer directly into the surgical cavity after a tumor is removed. Studies suggest that this approach can improve survival in some patients. 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.

Other Treatments

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.

Radioimmunotherapy with Monoclonal Antibodies. Radioimmunotherapy is showing special promise as a treatment approach to brain tumors. It typically uses monoclonal antibodies (MAbs), which are genetically engineered drugs designed to work against a specific target. MAbs are bound with radioactive substances 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 substances destroy the cell. The approach is essentially mini-radiation therapy without the damage or severe side effects of standard radiation treatments. A number of different radioimmunotherapies are being investigated, and trials of some are reporting improved survival rates in high-grade gliomas. Some experts believe this approach could prove to be the most effective therapy against these cancers.

Interleukins. Interleukins are natural proteins created by the immune system. Certain tumor cells carry receptors for specific interleukins, which are being investigated for a possible therapeutic role. For example, some drugs combine an interleukin with an agent that is toxic to cancer cells. The interleukin locks onto the receptor on the cancer cell and the toxic chemical enters the tumor with the intent to kill it. Some interleukins are also being investigated alone for their own tumor-cell killing properties.

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.

Cell Growth and Angiogenesis Inhibitors

Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Such agents, when effective, would starve tumors of vital nutrients and oxygen.Angiogenesis is particularly important in the growth of glioblastomas, the most malignant brain tumors. Of particular promise are agents that inhibit enzymes called tyrosine kinase, farnesyl protein transferase, and matrix metalloproteinase, which play critical roles in angiogenesis.

Farnesyl Protein Transferase Inhibitors. Farnesyl protein transferase inhibitors, such as tipifarnib, also called R115777 (Zarnestra) and lonafarnib (Sarasar), are drugs in a new class that block a mutated gene called the Ras gene, which is responsible for about 30% of cancers. Lonafarnib is in early trials in combination with temozolomide. Tipifarnib is also currently in early trials and may prove be effective as radiosensitizer.

Tyrosine Kinase Inhibitors. Drugs that target growth factors receptors such as tyrosine kinase, interfere with the pathway leading to angiogenesis. Some tyrosine kinase inhibitors, including erlotinib (Tarceva), imatinib (Gleevac), gefitinib (Iressa), and others are being investigated in early trials for brain tumor treatment. Side effects include rash, diarrhea, nausea and vomiting. Some of these drugs may reduce white blood cell count or cause liver damage. Researchers are trying to identify biomarkers that could help predict which patients would best respond to tyrosine kinase inhibitor therapy.

Matrix metalloproteinase Inhibitors. Matrix metalloproteinase is an important enzyme in angiogenesis. Inhibitors of these enzymes, including marimastat, metastat, and prinomastat, are in early trials. Marimastat has been studied and has shown some benefits in early trials for patients with recurrent glioblastoma and anaplastic gliomas, particularly in combination with temozolomide.

Phophoinositide 3-Kinse (Pi3K) Inhibitors. Rapamycin and its analog (CCI-779) inhibit Pi3K, an enzyme involved in cell growth. Early trials using CCI-779 are underway. (Another rapamycin analog, everolimus, has different effects but is also being studied for its actions in inhibiting cell growth.)

Other Drugs that Block Angiogenesis. Thalidomide was one of the first drugs used to inhibit angiogenesis and has undergone several trials. There is some evidence that it may work more effectively for metastasized brain tumors than primary tumors. Other agents in early trials with various effects on tumor growth include suramin, cilengitide, semaxanib, PTK787, and atrasentan.

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. Studies suggest that they have little benefits as single agents. Combination with radiotherapy and other drugs may hold promise.

Inactivated Viruses. Investigators are finding that certain genetically inactivated viruses, such as the poliovirus or herpesvirus, may prove to be valuable fighters of brain cancers. Such viruses can enter cells and destroy them but do not pose any danger for infection. For example one specially designed herpes virus targets the enzyme thymidine kinase (an enzyme that promotes tumor growth). Some researchers believe that a combination of this virus with retinoids may be effective with few serious side effects. Other viruses are being investigated. A drug based on this model is years away, however.

Immunnotoxins. Agents called immunotoxins use natural toxins to kill malignant brain cells.

Agents that employ diphtheria toxins, including TransMID-107R and DAB(389)EGF), are the first immunotoxins to show some promise. Clinical trials are investigating them for gliomas and metastatic brain cancers. Other toxins under investigation include irofulven (a mushroom toxin) and chlorotoxin (a substance derived from scorpions).

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.

Protein-Blocking Drug. 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 HABD (hyaluronan-binding domain), which 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. A 2003 study, for example, reported long-term survival in some patients, but it is not clear if such rates are any better than other treatments. The procedure has serious, sometimes life-threatening, side effects.

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. A 2003 study reported encouraging results, notably with patients with recurring glioblastoma multiforme. In the study, more than half of these patients survived for at least a year.

Treatment for Complications

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.

The ventricles of the brain are hollow chambers filled with cerebrospinal fluid (CSF), which supports the tissues of the brain.

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, irinotecan, interferon, and retinoic acid. Patients should discuss these interactions with their doctor.

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.

Resources

• www.abta.org -- American Brain Tumor Association
• www.cbtf.org -- Children's Brain Tumor Foundation
• www.virtualtrials.com -- Musella Foundation for Brain Tumor Research and Information
• www.braintumor.org -- National Brain Tumor Foundation
• www.neurosurgery.org -- American Association of Neurologic Surgeons
• www.cancer.org -- American Cancer Society
• www.cancer.gov -- National Cancer Institute
• www.asco.org -- American Society for Clinical Oncology
• www.cancer.gov/clinicaltrials -- Find clinical trials

References

Chang SM, Parney IF, Huang W, Anderson FA Jr, Asher AL, Bernstein M, et al; Glioma Outcomes Project Investigators. Patterns of care for adults with newly diagnosed malignant glioma. JAMA. 2005;293(5):557-564.

DeAngelis LM. Chemotherapy for brain tumors--a new beginning. N Engl J Med. 2005 Mar;352(10):1036-1038.

Fisher PG, Buffler PA. Malignant gliomas in 2005: where to GO from here? JAMA. 2005;293(5):615-617.

Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005;352(10):978-986.

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996.

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