Brain Cancer Overview

Cancers of the brain are the consequence of abnormal growths of cells in the brain. Brain cancers can arise from primary brain cells, from the cells that form other brain components (for example, membranes, blood vessels), or from the growth of cancer cells from other organs that have spread to the brain by the bloodstream (metastatic brain cancer).

• Although many growths in the brain are popularly called brain tumors, not all brain tumors are cancerous. Cancer is a term reserved for malignant tumors.



• Malignant tumors grow and spread aggressively, overpowering healthy cells by taking their space, blood, and nutrients. (Like all cells of the body, tumor cells need blood and nutrients to survive.) This is especially a problem in the brain, as the added growth within the closed confines of the skull can lead to an increase in intracranial pressure or the distortion of surrounding vital structures, causing their malfunction.



• Tumors that do not grow aggressively are called benign. Almost all tumors that begin in the brain do not spread to other parts of the body. The major differences between benign and malignant tumors is that malignant tumors can invade the brain tissues and grow rapidly.



• In general, a benign tumor is less serious than a malignant tumor. However, a benign tumor can still cause many problems in the brain.

Primary brain tumors

The brain is made up of many different types of cells.

• Cancers occur when one type of cell transforms and loses its normal characteristics. Once transformed, the cells grow and multiply in abnormal ways.



• As these abnormal cells grow, they become a mass of cells, or tumor.



• Brain tumors that result from this transformation and abnormal growth of brain cells are called primary brain tumors because they originate in the brain.



• The most common primary brain tumors are gliomas, meningiomas, pituitary adenomas, vestibular schwannomas, primary CNS lymphomas, and primitive neuroectodermal tumors (medulloblastomas). The term glioma is an expansive one since it includes numerous subtypes, including astrocytomas, oligodendrogliomas, ependymomas, and choroid plexus papillomas.



• These primary tumors are named after the part of the brain or the type of brain cell from which they arise.

Brain tumors vary in their growth rate and ability to cause symptoms. The cells in fast growing, aggressive tumors usually appear abnormal microscopically. The National Cancer Institute (NCI) uses a grading system to classify tumors. The NCI lists the following grades:

• Grade I: The tissue is benign. The cells look nearly like normal brain cells, and cell growth is slow.



• Grade II: The tissue is malignant. The cells look less like normal cells than do the cells in a grade I tumor.



• Grade III: The malignant tissue has cells that look very different from normal cells. The abnormal cells are actively growing. These cells are termed anaplastic.



• Grade IV: The malignant tissue has cells that look most abnormal and tend to grow very fast.

Metastatic brain tumors

Metastatic brain tumors are made of cancerous cells that spread through the bloodstream from a tumor located elsewhere in the body. The most common cancers that spread to the brain are those arising from the lung, breast, and kidney as well as malignant melanoma. The cells spread to the brain from another tumor in a process called metastasis. The process metastasis occurs when cancer cells leave the primary cancer tissue and enter either the lymphatic system to reach the blood or the bloodstream directly. These cancer cells eventually reach the brain tissue through the bloodstream where they develop into tumors.

Metastatic brain tumors are the most common type of tumor found in the brain and are much more common than primary brain tumors. Metastatic tumors are usually named after the type of tissue from which the original cancer cells arose (for example, metastatic lung or breast cancer). Brain blood flow usually determines where the metastatic cancer cells will lodge in the brain; about 85% locate in the cerebrum (the largest portion of the brain, located in the upper part of the skull cavity). Unfortunately, the majority of metastatic brain tumors occur at more than one site in the brain tissue.

In the United States, brain tumors are estimated to develop in about 22,000 people in 2009.

Brain Cancer Causes

As with tumors elsewhere in the body, the exact cause of most brain tumors is unknown.

The following factors have been proposed as possible risk factors for primary brain tumors, but whether these factors actually increase an individual's risk of a brain tumor is not known for sure.

• Radiation to the head



• An inherited (genetic) risk



• HIV infection



• Cigarette smoking



• Environmental toxins (for example, chemicals used in oil refineries, embalming chemicals, rubber industry chemicals)

Brain Cancer Symptoms

Not all brain tumors cause symptoms, and some (such as tumors of the pituitary gland that cause no symptoms) are found mainly after death. The symptoms of brain tumors are numerous and not specific to brain tumors, meaning they can be caused by many other illnesses as well. The only way to know for sure what is causing the symptoms is to undergo diagnostic testing.

• The symptoms are caused by the tumor pressing on or encroaching on other parts of the brain and keeping them from functioning normally.



• Some symptoms are caused by swelling in the brain caused by the tumor or surrounding inflammation.



• The symptoms of primary and metastatic brain cancers are similar.

The following symptoms are most common:

• Headache



• Weakness



• Clumsiness



• Difficulty walking



• Seizures

Other nonspecific symptoms and signs include the following:

• Altered mental status: changes in concentration, memory, attention, or alertness



• Nausea, vomiting: especially early in the morning



• Abnormalities in vision



• Difficulty with speech



• Gradual changes in intellectual or emotional capacity

In many people, the onset of these symptoms is very gradual and may be overlooked by both the person with the brain tumor and the person's family members, even for long time periods. Occasionally, however, these symptoms appear more rapidly. In some instances, the person acts as if he or she is having a stroke.

When to Seek Medical Care

See your health-care provider right away if you have any of the following symptoms:

• Unexplained, persistent vomiting



• Double vision or unexplained blurring of vision, especially on only one side



• Lethargy or increased sleepiness



• New seizures



• New pattern or type of headaches, especially early morning headaches

Although headaches are thought to be a common symptom of brain cancer, they may not occur until late in the progression of the disease. If any significant change in a person's headache pattern occurs rapidly, health-care providers may suggest that you go the emergency department. If a person has a known brain tumor, any new symptoms or relatively sudden or rapid worsening of symptoms also warrants a trip to the nearest hospital emergency department. Be on the lookout for the following new symptoms:

• Seizures



• Changes in mental status, such as excessive sleepiness, memory problems, or inability to concentrate



• Visual changes or other sensory problems



• Difficulty with speech or in expressing yourself



• Changes in behavior or personality



• Clumsiness or difficulty walking



• Nausea or vomiting (especially in middle-aged or older people)



• Sudden onset of fever, especially after chemotherapy

Exams and Tests

If findings of a medical interview and physical examination suggest to the health-care provider that a person may have a problem in the brain or brain stem, additional tests may be done.

• Many people will have a CT scan of the brain.



• This test is like an X-ray but shows more detail in three dimensions.



• Usually, a harmless dye is injected into the bloodstream to highlight abnormalities on the scan.

People with brain cancer often have other medical problems; therefore, routine laboratory tests may be performed.

• These include analysis of blood, electrolytes, liver function tests, and a blood coagulation profile.



• If the person has mental-status change as the main symptom, blood or urine tests may be done to rule out drug use.

The standard way of evaluating the nature and extent of a brain tumor is an MRI scan.

• This is because MRI has a higher sensitivity for detecting the presence and characteristics of a tumor. Specifically, the relationship of the tumor to the surrounding brain, the brain coverings, cerebrospinal fluid spaces, and vascular structures is assessed to come up with a provisional diagnosis of the nature of the tumor.



• Currently, however, many institutions still use the CT scan as a screening test for tumors.

If CT or MRI scans indicate the presence of a brain tumor, the person will be referred to a specialist in brain surgery (a neurosurgeon). If one is available in the area, the person may also be referred to a specialist in the chemotherapeutic treatment of brain tumors (a neuro-oncologist).

The next step in diagnosis is confirmation that the person has cancer in the brain. A small sample of the tumor (a biopsy) is taken to identify the type of tumor.

• The most widely used technique for obtaining a biopsy is a surgical procedure called a craniotomy. The skull is opened, usually with the intention of removing the whole tumor if possible. A biopsy is then taken from the tumor.



• If the surgeon is unable to remove the entire tumor, a small piece of the tumor is removed.



• In some cases, it is possible to collect a biopsy without opening the skull. The exact location of the tumor in the brain is determined stereotactically, that is, by using CT or MRI scans while the head is held still in a frame. A small hole is then made in the skull and a needle guided through the hole to the tumor. The needle collects the biopsy and is removed. This technique is called stereotaxis, or stereotactic biopsy. This process does not treat the tumor and is generally reserved for situations in which the tumor is either inaccessible or is thought to be sensitive to radiation therapy (such as CNS lymphoma or pineal germ cell tumor).



• The biopsy is examined under a microscope by a pathologist (a physician who specializes in diagnosing diseases by looking at cells and tissues) and usually assigned a NCI grade.

Brain Cancer Treatment

Treatment for brain cancer should be individualized for each patient. Treatment regimens are based on the patient's age and general health status as well as the size, location, type, and grade of the tumor. In most cases of brain cancer, surgery, radiation, and chemotherapy are the main types of treatment. Often, more than one treatment type is used. The treatment types are further described below.

The patient, family, and friends will have many questions about the tumor, the treatment, how treatment will affect the person, and the person's long-term outlook. Members of the person's health-care team are the best source of this information. Don't hesitate to ask them any questions.

Types of Treatments for Brain Cancer

Treatment of brain cancer is usually complex. Most treatment plans involve several consulting doctors.

• The team of doctors includes neurosurgeons (surgical specialists in the brain and nervous system), oncologists, radiation oncologists (doctors who practice radiation therapy), and of course, your primary health-care provider. A patient's team may include a dietitian, a social worker, a physical therapist, and probably other specialists.



• The treatment protocols vary widely according to the location of the tumor, its size, grade, and type, the patient's age, and any additional medical problems that the person may have.



• The most widely used treatments are surgery, radiation therapy, and chemotherapy. In some cases, more than one of these treatment types are used.

Most people with a brain tumor undergo surgery.

• The purposes of surgery are to confirm that the abnormality seen on the brain scan is indeed a tumor, to assign a grade to the tumor, and to remove the tumor. If the tumor cannot be removed, the surgeon will take a sample of the tumor to identify its type and grade.



• In some cases, mostly in benign tumors, symptoms can be completely cured by surgical removal of the tumor. A neurosurgeon will attempt to remove the tumor when possible.

Patients may undergo several treatments and procedures before surgery.

• They may be given a steroid drug, such as dexamethasone (Decadron), to relieve swelling.



• They may be treated with an anticonvulsant drug, such as levetiracetam (Keppra), phenytoin (Dilantin), or carbamazepine (Tegretol), to relieve or prevent seizures.

Overview of surgery for resection of brain tumor

The intent of surgery for tumors is to remove as much of the tumor as is safely possible with the minimal possible loss in brain function. The large majority of patients undergo this procedure under general anesthesia. Some surgeries are done awake or under light sedation for the purpose of mapping language function. For surgery done under general anesthesia, an endotracheal tube is placed, while for those done awake, a laryngeal mask airway (or no airway) is placed and the patient is deeply sedated. The head is appropriately positioned using a clamp system that holds the skull motionless. An image-guided navigation system is often used to help determine the precise location of the incision. The scalp is prepped, after the hair is clipped, the planned incision line is infiltrated with local anesthesia, and the scalp is then incised and pushed aside to expose the skull bone. A portion of the skull is temporarily cut away and the lining tissues of the brain are opened. If it is necessary to determine whether brain function is compromised, the patient is awakened from sedation in order to respond as mapping procedures are carried out.

In either case, tumor resection is then carried out. A portion of the tumor is usually sent to the pathologist for analysis. The surgeon may also decide to place biodegradable polymer wafers that deliver chemotherapy drugs (Gliadel wafers) into the tumor cavity. Once the tumor resection is complete, the membranes surrounding the brain are closed and the skull is closed, often with the use of titanium plates and screws that help hold it rigidly in its desired position. The scalp is closed; some surgeons use drains placed under the scalp for a day or two after surgery to minimize the accumulation of blood or fluid.

• Stereotactic radiosurgery is a newer "knifeless" technique that destroys a brain tumor without opening the skull. CT or MRI scan is used to pinpoint the exact location of the tumor in the brain. High-energy radiation beams are trained on the tumor from different angles. The radiation destroys the tumor. Equipment used to do radiosurgery varies in its radiation source; a gamma knife uses focused gamma rays, and a linear accelerator uses photons, while heavy-charged particle radiosurgery uses a proton beam.



• The advantages of knifeless procedures are that they have fewer complications and the recovery time is much shorter. Disadvantages include the lack of tissue available to send to a pathologist for diagnosis and brain swelling that can occur after the radiation therapy.



• If patients have excess cerebrospinal fluid buildup, a thin plastic tube called a shunt may be placed to drain the fluid. One end of the shunt is placed in the cavity where fluid collects, and the other is threaded under the skin to another part of the body. The fluid drains from the brain to a site from which the fluid can be easily eliminated.

Radiation therapy (also called radiotherapy) is the use of high-energy rays to kill tumor cells and stop them from growing and multiplying.

• Radiation therapy is sometimes used for people who cannot undergo surgery. In other cases, it is used after surgery to kill any tumor cells that may remain.



• Radiation therapy is a local therapy. This means that it affects only cells in its path. It does not harm cells elsewhere in the body or even elsewhere in the brain.

Radiation can be administered in either of two ways.

• External radiation uses a high-energy beam of radiation targeted at the tumor. The beam travels through the skin, the skull, healthy brain tissue, and other tissues to get at the tumor. The treatments are usually given five days a week for about four to six weeks. Each treatment takes only a few minutes.



• Internal or implant radiation uses a tiny radioactive capsule that is placed inside the tumor itself. The radiation emitted from the capsule destroys the tumor. The radioactivity of the capsule decreases a little bit each day; the amount of radioactivity of the capsule is carefully calculated to run out when the optimal dose has been given. You need to stay in the hospital for several days while receiving this treatment.

Chemotherapy is the use of powerful drugs to kill tumor cells.

• A single drug or a combination may be used.



• The drugs are given by mouth or through an IV line. Two drugs, temozolomide (Temodar) and bevacizumab (Avastin), have recently been approved for the treatment of malignant gliomas. They are more effective, and fewer adverse effects when compared with older drugs. Temozolomide has another advantage in that it is administered orally, eliminating the need for intravenous lines and hospital stays for chemotherapy.



• Chemotherapy is usually given in cycles. A cycle consists of a short period of intensive treatment followed by a period of rest and recovery. Each cycle lasts a few weeks.



• Most regimens are designed so that two to four cycles are completed. There is then a break in the treatment to see how the tumor has responded to the therapy.



• The side effects of chemotherapy are well known and are very difficult to tolerate for some people. They include nausea and vomiting, mouth sores, loss of appetite, loss of hair, and many others. Some of these side effects can be relieved or improved by medication.

New therapies for cancer are being developed all the time. When a therapy shows promise, it is studied in laboratories and improved as much as possible. It is then tested on people with cancer; these tests are called clinical trials.

• Clinical trials are available for virtually every kind of cancer.



• The advantage of clinical trials is that they offer new therapies that may be more effective than existing therapies or have fewer side effects.



• The disadvantage is that the therapy has not been proven to work or does not work in everyone.



• Many people with cancer are eligible for participation in clinical trials.



• To find out more, ask your health-care provider. A list of clinical trials is available at the web site of the National Cancer Institute.

Side Effects of Brain Cancer Treatments

Treatment plans try to limit or reduce side effects associated with brain cancer treatment. However, most patients will experience some side effects; some side effects can be severe. People who undergo brain cancer treatment should ask about the potential side effects and help decide if the proposed treatment(s) will be worth the benefits and what to do if side effects appear.

Side effects of chemotherapy may include nausea, vomiting, hair loss, and weakness. The immune system is usually suppressed, which makes the person more susceptible to infections. Other organ systems such as the kidneys or reproductive organs may be damaged. Although these side effects usually decline as treatment ends, some may not, especially if other organ systems are damaged.

Radiation therapy has side effects similar to those listed above for chemotherapy, but because some organ systems do not obtain a direct radiation dose, the side effects can be less than those of chemotherapy. However, skin damage (reddish or darkened) and skin sensitivity may occur. Hair loss can also occur, especially in areas where the radiation enters the body; some hair loss is permanent.

Surgery can cause both temporary and permanent changes. Side effects such as brain swelling, damage to normal tissue, mental-status changes, muscle weakness, or changes in any brain-controlled function may occur. Although such side effects usually decline over time, some may become permanent.

Patients and brain cancer team members should carefully consider side effects; often some of them can be reduced by medical treatment and may not be permanent. Brain cancer patients who are candidates for treatment should understand that without either surgery, chemotherapy, or radiation therapy (or combinations of them) the prognosis or outlook for most patients is poor.

Prevention

In general, there is no known way to prevent brain cancers. However, early diagnosis and treatment of tumors that tend to metastasize to the brain may reduce the risk of metastatic brain tumors. Avoiding or reducing contact with radiation (especially to the head) and avoiding toxic chemicals associated with the oil and rubber industry, embalming chemicals, and other environmental toxins may help prevent brain cancers. Avoiding HIV infection is also suggested. The popular press and some web sites suggest that avoiding cell phone use and using a macrobiotic diet will help avoid brain cancer. Currently, there is no good evidence for these claims. However, for those who want to minimize any radiation dose from cell phones, the reader can consult the web for a list of phones that produce the highest and lowest radiation levels.

Prognosis

The major factors that influence survival seem to be the type of cancer, its location, whether it can be surgically removed or reduced, and the age and overall health status of the patient.

• The long-term survival rate (greater than five years) for people with primary brain cancer varies from less than 10% to about 32%, despite aggressive surgery, radiation, and chemotherapy treatments.



• Treatments do prolong survival over the short term and, perhaps more importantly, improve quality of life.

Most people with metastatic brain cancer die from their primary cancer rather than from the brain lesions.

• Radiation and chemotherapy can increase life expectancy modestly.



• People who have seizures generally do poorly over the following six months.

Despite seemingly dismal chances of long-term survival, these chances are clearly greater with treatment than without. Treatment options and best-estimated prognosis should be discussed with the patient's cancer team.