Metastatic Tumors to the Brain and Spine

All rights reserved. Copyright © 1993 by American Brain Tumor Association ISBN 0-944093-26-4 Reproduction without prior written permission is prohibited.

Printing of this publication was made possible in part by a generous grant in loving memory of Earl H. Segal

• HOW TO USE THIS DOCUMENT
• INTRODUCTION
• 1. ABOUT METASTASIS
• 2. INCIDENCE
• 3. SYMPTOMS
• 4. DIAGNOSIS
• 5. TREATMENT
• 6. COMMON CENTRAL NERVOUS SYSTEM METASTASES BY PRIMARY CANCER
• 7. WHAT YOU CAN DO TO HELP YOURSELF
• 8. CANCER STATISTICS
• GLOSSARY
• ACKNOWLEDGEMENTS

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HOW TO USE THIS BOOKLET

We urge you to read the Introduction and Chapters one through five. Those chapters contain explanations and information that apply to metastases to the brain and spine, regardless of the primary cancer. Chapter six contains information specific to selected primary cancers.

Terms printed in parentheses are technical names for the words used before them.

All definitions in parentheses and explanations are in the glossary . The glossary also contains additional terms.

To obtain copies of our printed publications, or to request any of our patient services, please contact the ABTA.

INTRODUCTION

Cancer patients like you are living longer now because cancer treatment is more effective than in the past. Probably, that is the reason the number of people with spread [metastasis Metastasis is singular; metastases is plural.] to the central nervous system [The Central Nervous System (CNS) is the brain, cranial nerves, and spinal cord.] (CNS) is increasing.

Many, if not most of these metastases, can be controlled or eliminated with aggressive treatment.

If your cancer has spread to the central nervous system, we hope this booklet will help you discuss treatment options with your doctors and nurses.

If you have a metastatic central nervous system tumor but your primary cancer is not yet known, we hope this booklet will help you understand the purpose of the various tests your doctors are requesting.

If your type of cancer has a tendency to spread to the central nervous system, we hope you will find the information in this booklet useful.

1. ABOUT METASTASIS

DEFINITION

Many cancers metastasize. Metastasis is the spread of cancer from one part of the body to another. The original location is called the primary tumor. Metastatic tumors are tumors that arise at sites away from the original location.

Cancer cells from the primary site can break away and enter the body's circulatory system blood stream [arteries and veins], lymph system or spinal fluid [Spinal fluid is the liquid that flows between the layers of the meninges. It circulates around the brain and spinal cord.] and travel to distant locations. Stray cancer cells are often destroyed by the immune system. But, if the number of stray cells is too large, the immune system may be overwhelmed and allow some cancer cells to survive. Those cells will grow at another site. The most common pathway for metastasis to the central nervous system is via the blood stream.

Many variables determine where metastatic tumors grow. Often, the metastatic location is the nearest cluster of small blood vessels found by the circulating cancer cells. Thus lung cancer commonly metastasizes to the brain; colon cancer commonly metastasizes to the liver. Or, the cancer may have a preferred site of metastasis. The brain is a preferred site for melanoma and small cell lung cancer. A metastasis of a metastasis may develop as well a colon cancer may metastasize to the liver which in turn may metastasize to the lung which may in turn metastasize to the brain.

Metastasis to the central nervous system There are three forms of metastasis to the central nervous system:

METASTATIC BRAIN TUMORS

Tumors in the brain are the most common form of central nervous system metastasis. There may be single or multiple tumors. Metastatic brain tumors often have distinct characteristics that can be observed on scans and help distinguish them from primary brain tumors [Primary brain tumors originate in the brain; metastatic brain tumors originate elsewhere in the body]. However, an exact determination of the type of tumor can usually be made only after a sample of the tumor is examined under the microscope.

SPINAL FLUID METASTASES

cancer cells circulating in the spinal fluid [meningeal carcinomatosis or lymphomatosis The widespread presence of cancer cells in the spinal fluid is called meningeal carcinomatosis. An older term for this condition is leptomeningeal metastasis. Another term that may be used is carcinomatous meningitis. Meningeal lymphomatosis is the widespread pressence of lymphoma cells in the spinal fluid.]

Spinal fluid metastases may occur by themselves or in addition to tumors in the brain. Acute lymphocytic leukemia and high-grade non-Hodgkin's lymphomas often spread only to the spinal fluid. Small cell lung cancer, breast cancer and melanoma commonly involve both the brain and spinal fluid. Non-small cell lung cancer usually affects only the brain.

METASTATIC SPINAL TUMORS Metastatic spinal tumors are usually extra-dural they grow outside the dura mater in the bones of the spine. Those tumors affect the spinal cord and spinal nerves by causing pressure

(compression).

About one-third of people with central nervous system metastases have not been previously diagnosed with cancer. Their CNS symptoms are the first indication of cancer. And, in half of those people, the primary site will never be found.

2. INCIDENCE

INTRODUCTION

Central nervous system metastases may be present before cancer is found elsewhere; when you are first diagnosed with cancer; or most commonly, after your cancer has been found and treated. Eighty-one percent of people with central nervous system metastases are diagnosed after their primary cancer has been diagnosed and treated. The thirty-five percent of patients with metastatic brain tumors who have not been previously diagnosed with cancer will undergo tests to determine the primary site.

Some people will have central nervous system metastases without their primary site developing. Those patients may have a very effective immune system which has destroyed the cancer at its original location.

Certain cancers tend to metastasize earlier than others. Lung cancer and renal (kidney) cancer tend to spread sooner; breast, melanoma and colon cancer metastases to the central nervous system occur later.

METASTATIC BRAIN TUMORS

Lung, colon and renal cancers account for eighty percent of metastatic brain tumors in men. Breast, lung, colon and melanoma cancers account for eighty percent of metastatic brain tumors in women.

SPINAL FLUID METASTASES

Four percent of people whose cancer has spread to the central nervous system have cancer cells circulating in their spinal fluid. Non-Hodgkin's lymphoma, small cell lung cancer, breast cancer, leukemia, lymphoma and melanoma most frequently spread to the spinal fluid. Fewer than ten percent of acute lymphocytic leukemia patients have metastases at the time of their initial diagnosis.

METASTATIC SPINAL TUMORS

Spinal metastases occur in five percent of cancer patients, most commonly in those with breast cancer, prostate cancer and multiple myeloma. Tumors growing in the bones of the spine (vertebrae) may press on or displace the adjacent spinal cord if they are large.

3. SYMPTOMS

INTRODUCTION

There are three causes of symptoms of central nervous system metastasis: those caused by mass effect [Mass effect is caused by blockage of spinal fluid, space taken up in the skull by a growing tumor, or swelling due to excess fluid (edema). Mass effect results in increased intracranial pressure.]; those caused by irritation or destruction of brain cells; and those caused by local pressure or displacement due to a tumor growing outside the brain or spinal cord.

ABOUT EDEMA

Metastatic brain tumors commonly cause widespread swelling (edema). Edema is an increase in the amount of water in the brain. Vasogenic edema, the type caused by metastatic tumors, is due to damaged blood vessel linings. That damage allows substances to enter the brain which would normally be prevented. The water content increases to dilute those substances. That results in increased intracranial pressure, because the bony skull cannot expand to accommodate the enlarged size of its contents. The excess fluid may travel to distant sites in the brain, far away from the site of the tumor and the damaged blood vessels.

While specific signs and symptoms [Signs are what the doctor can observe, either directly or as the result of various tests; symptoms are the sensations and feelings you describe. We use symptoms for both signs and symptoms.] may indicate a brain tumor, a definite diagnosis cannot be made based on those indications alone because many other conditions have similar symptoms. Tests used to confirm the diagnosis are described in the next section of this booklet.

SYMPTOMS OF METASTATIC BRAIN TUMORS HEADACHE:

Headache is caused by stretching of sensitive structures such as blood vessels or nerves due to edema, spinal fluid obstruction or tumor growth, or by injury to the brain caused by the tumor. Initially, the headache comes and goes, and is usually more common in the morning, just after awakening. It gradually increases in duration and frequency.

MUSCLE WEAKNESS:

Localized (focal) weakness or weakness on one side of the body (hemiparesis) may occur. That is caused by irritation or injury to specific areas of the brain by the tumor.

BEHAVIORAL CHANGES:

Common behavioral changes include changes in judgment, reasoning, behavior; impaired memory; emotional changes such as rapid mood shifts; and confusion. Those symptoms are caused by edema and increased intracranial pressure.

PHYSICAL CHANGES:

Physical changes include changes in vision, language disturbances (dysphasia [Dysphasia is the impairment of the ability to speak or write, to understand speech or written words. Dysphasia may be moderate or severe.]), sensory loss, and gait disorders (ataxia [Ataxia refers to a clumsy, uncoordinated walk and problems with balance.]). Those changes are due to increased intracranial pressure or brain irritation. Ataxia is more common in people with spinal fluid obstruction, or with tumors involving the cerebellum. Cerebellar tumors often cause dizziness and vomiting.

Seizures [Seizures are convulsions. They are due to temporary disruption in the electrical activity of the brain.] Seizures are caused by brain irritation or increased intracranial pressure. They may be the first indication of brain metastases, particularly in people with melanoma.

Papilledema (swelling of the optic nerve)

Papilledema is due to increased intracranial pressure.

SYMPTOMS OF INCREASED INTRACRANIAL PRESSURE The common symptoms of increased intracranial pressure are listlessness, confusion, and headache.

The most common symptoms of brain metastasis are headache, muscle weakness and behavioral disturbances. These problems indicate to your doctor the need to test for metastatic brain tumors, particularly if you have already been diagnosed with cancer.

SYMPTOMS OF SPINAL FLUID METASTASES Spinal fluid metastases may occur by themselves, or in addition to brain tumors. Common symptoms of cancer cells circulating in the spinal fluid are: pain, particularly in the neck and back; headache; progressive muscle weakness and loss of sensation due to spinal and cranial nerve impairments. The specific areas of your body affected by weakness and sensory loss depend on which nerves are affected. Other common symptoms include changes in behavior confusion, listlessness, impaired memory and judgment, and frequent mood changes. Seizures may also occur. Hydrocephalus [Hydrocephalus is excess water in the brain due to blockage of spinal fluid pathways.] occurs in half the people with spinal fluid metastases.

Symptoms of spinal fluid metastases are caused by irritation or compression of the brain and/or spinal cord and increased intracranial pressure.

This type of metastasis is more common in people with leukemia and lymphoma.

SYMPTOMS OF METASTATIC SPINAL TUMORS The usual indication of metastasis to the spine is pain directly over the area of metastasis or radiating along the nerve. The pain often precedes other symptoms by days or even weeks. The pain may be worsened by standing, by lifting heavy objects, or any movement. Bed rest may relieve the pain initially, but it usually progresses. Later symptoms are progressive muscle weakness, loss of sensation and loss of bladder or bowel control.

4. DIAGNOSIS

INTRODUCTION

The initial diagnosis of central nervous system metastasis is based on your medical history, a neurologic examination, and a range of tests. Those tests may include x-rays, blood, urine and stool tests, spinal fluid tests, and CT or MRI scans with contrast enhancement.

Various conditions may imitate the symptoms of central nervous system metastases. These include primary brain tumors, infections, cysts, stroke, and complications from medications. A correct diagnosis is important because treatment depends on it.

The exact location of the metastasis must be determined during the diagnostic process. Treatment recommendations are based on the location of the tumor and if cancer cells have entered the spinal fluid. The radiation therapist needs location information for treatment planning; the surgeon needs it to plan the operative approach and technique.

About one-third of the people with symptoms of central nervous system metastases have not been previously diagnosed with cancer. If there is no history of cancer, it is necessary to undergo more extensive testing to determine the primary cancer. A chest x-ray, bone or liver scans, an abdominal CT scan and mammography may be indicated, depending on the symptoms. Even after thorough testing, it is not always possible to determine the original cancer. The primary cancer site is never found in fifteen percent of people with central nervous system metastases.

DIAGNOSIS OF METASTATIC BRAIN TUMORS The doctor suspects a metastatic brain tumor rather than a primary brain tumor if there has been a prior diagnosis of cancer. That suspicion is furthered by the nature of the symptoms. The MRI [MRI is Magnetic Resonance Imaging. MRI is a scanning device that uses a magnetic field, radio waves and a computer. Signals emitted by normal and diseased tissue during the scan are assembled into an image. Contrast enhancement is the use of an agent such as Gadolinium-DTPA, administered shortly before the MRI is performed, to enhance the images obtained so that tumors are more readily detected and their characteristics are move obvious.] scan with contrast enhancement is the primary diagnostic tool for metastatic brain tumors.

Metastatic brain tumors have distinctive characteristics that can be observed on scans. Those characteristics suggest a metastatic rather than a primary brain tumor.

CHARACTERISTICS OF METASTATIC BRAIN TUMORS:

They most frequently occur in the cerebrum (80%), the cerebellum (13-16%), and the brain stem (3%).

They are usually solid and spherical in shape with well-defined margins, their center is often soft and filled with dead cells, and they have a zone of active tumor cells that frequently appear as a ringlike structure on the scan.

They commonly grow in the junction between the white and grey matter, the area with the most blood vessels.

Fifty percent of the time multiple tumors are present, particularly in people with non-small cell lung cancer, breast cancer or melanoma. Renal and colon cancers are more likely to give rise to single tumors.

They are usually accompanied by widespread edema.

An exact diagnosis of brain metastasis requires microscopic examination of a sample of the tumor tissue. A biopsy [Biopsy is the process of removing a sample of tumor tissue to establish an exact diagnosis. The tumor sample is obtained during a surgical procedure and then examined under a microscope in the laboratory. Biopsies may either by open or needle and often are performed using stereotactic techniques.] is sometimes recommended to eliminate the chance of misdiagnosis.

DIAGNOSIS OF SPINAL FLUID METASTASES A lumbar puncture [Lumbar puncture, also called spinal tap, is the insertion of a hollow needle into the subarachnoid space of the lumbar spine to withdraw a sample of spinal fluid for examination in the laboratory. A local anesthetic is administered prior to the procedure.]

(LP) is performed to obtain a sample of spinal fluid. The sample is examined in the laboratory for the presence of cancer cells, protein, sugar and tumor markers. (Tumor markers are substances that identify the presence of a tumor, and possibly the tumor type.) Two or more samplings of spinal fluid may be required for definitive results. LP is routinely performed if spinal fluid metastasis is suspected. LP is not routinely performed in other circumstances as it may be risky in people with increased intracranial pressure.

Myelography [Myelography is a specialized x-ray technique. A radio-opaque substance injected into the subarachnoid space followed by x-rays may depict blockage or growths.] also may be required for diagnosis if meningeal metastases are suspected.

DIAGNOSIS OF METASTATIC SPINAL TUMORS Spinal tumors occur most commonly in the vertebrae of the thoracic region of the spine (60%), followed by the cervical and lumbar regions (20% each). Symptoms are due to compression of the spinal cord and nerve roots.

5. TREATMENT

INTRODUCTION

Treatment goals vary depending on the patient and other factors. The goal may be cure, improvement, or relief of symptoms (palliation).

FACTORS CONSIDERED BEFORE TREATMENT IS RECOMMENDED

The recommended treatment is based on answers to the following questions:

Are there single or multiple tumors? Where is the tumor located? Surgery is often preferred for single, accessible [Accessible tumors can be approached surgically without causing undue neurological damage.] tumors if other factors are favorable.

Is the primary cancer under control? If it is not, there is a chance that new metastatic tumors will form. Radiation therapy may be more practical in this instance.

What is the primary cancer? Some metastases, such as those from small cell lung cancer or lymphoma, are very responsive to radiation therapy and surgery is often not considered. Other types of metastases may respond to systemic [Systemic chemotherapy is delivered in the bloodstream or orally as opposed to delivery to the central nervous system directly.] chemotherapy.

What is the patient's age and general health?

There are different classification systems used to evaluate general health. One of these is the Karnofsky Performance Scale.

• 100 Normal; no complaints; no evidence of disease
• 90 Able to carry on normal activity; minor signs or symptoms of disease
• 80 Normal activity with effort; some signs or symptoms of disease
• 70 Cares for self; unable to carry on normal activity or to do active work
• 60 Requires occasional assistance but is able to care for most of needs

Generally, if the Karnofsky score is greater than 60 or 70, surgery could be considered, if other factors are favorable.

Other performance scales are used by various institutions. They are all similar, however.

How long is it since the primary cancer was diagnosed? If it has been a long time, aggressive treatment of your brain tumor in the form of both surgery and radiation may result in long term control of the disease because the cancer is probably somewhat slow growing.

Are cancer cells present in the spinal fluid? Chemotherapy followed by radiation therapy may be beneficial in that situation.

TREATMENT

Treatment modalities [Modalities is plural for modality. Modality is the treatment method: surgery; irradiation; hormone therapy; chemotherapy; immunotherapy; etc.] for central nervous system metastases

Steroids

Steroids act rapidly to decrease the symptoms of increased intracranial pressure due to the edema that accompanies metastatic brain tumors. Although steroids do not kill cancer cells, they can decrease the amount of leakage from damaged blood vessel linings, decrease the production of spinal fluid, and increase blood flow in the brain. Improvement is noticeable within six to twenty-four hours relief of headache, confusion and other behavioral problems. This therapy is effective in sixty to eighty percent of people with metastatic brain tumors. Dexamethasone (Decadron),

methylprednisolone, and prednisone are steroids. Steroid use is monitored by the doctor because of its potential side effects.

Steroids are frequently prescribed during the course of radiation therapy, to reduce the swelling caused by that therapy.

Osmotherapy

Mannitol and glycerol are agents used to treat edema and intracranial pressure by removing water from the brain. Glycerol is given orally; mannitol is administered into a vein. Osmotics have high concentrations of substances that the body seeks to dilute thus drawing water out of the brain in the exact opposite way the edema was formed originally.

Conventional radiation therapy Radiation kills cancer cells directly, or interferes with their growth. The tumor shrinks as cells die and are disposed of. Radiation therapy is the most common treatment for CNS metastases. It may also be the only treatment used. It is the treatment of choice for patients with small cell lung cancer and lymphoma metastases, because those tumors are very radiosensitive [Radiosensitive tumors usually respond positively to radiation therapy the tumors shrink.]. Sixty to eighty-five percent of all patients respond to irradiation of their metastases by experiencing immediate relief of their symptoms.

METASTATIC BRAIN TUMORS In general, conventional, external irradiation for brain metastases is a total dose of 3000 cGy [cGy is the standard measurement of ionizing radiation, and stands for centiGray.], to the entire brain. It is delivered in 300 cGy portions five days a week, for two weeks. This may be followed by a booster dose of 900 cGy to the tumor. There are slight variations of this dosage plan in use. Radiation therapy often follows brain surgery for those people who have surgery.

SPINAL FLUID METASTASES

If there are cancer cells in the spinal fluid and there is no brain tumor, treatment will usually consist of a total dose of 2400 cGy, divided into eight portions, together with intrathecal [Intrathecal drug administration into the spinal fluid. An Ommaya reservoir or a ventricular access device may be used to delivery the drug into a ventricle. This is called intraventricular delivery. The drug then circulates from the ventricle throughout the spinal fluid.] chemotherapy.

METASTATIC SPINAL TUMORS The usual treatment for spinal metastases is radiation, followed by systemic chemotherapy. Surgery is also advised for some people. Hormone therapy may be administered, depending on the primary cancer.

NEWER FORMS OF RADIATION THERAPY Several newer forms of radiation therapy are under investigation. These include:

STEREOTACTIC RADIOSURGERY

Stereotactic radiosurgery uses a large number of narrow, precisely aimed, highly focused beams of ionizing radiation to destroy brain tumors. The beams are aimed from many directions circling the head, and all converge at a specific point the tumor. That method necessitates knowledge of the exact location of the tumor and of any critical brain structures between the tumor and the scalp. This treatment is planned so that each part of the brain through which the beams pass receives only a small amount of the total dose. At the same time, it allows for a large dose to be delivered to the tumor itself. Conventional, external radiation to the entire brain often follows the radiosurgery.

There are three methods of delivering stereotactic radiosurgery: Gamma Unit, adapted linear accelerators and cyclotrons.

The size of the tumor is a determining factor in deciding whether stereotactic radiosurgery is appropriate. Is the tumor small having a diameter of about one inch or less (three centimeters)? If so, radiosurgery may be appropriate. Larger tumors require more beams of radiation. That results in a greater effect on normal brain tissue. Other factors need to be considered to determine if this form of treatment is appropriate. Are there multiple tumors? If so, what is their size and location? It may be possible to treat as many as three or four tumors, depending on their locations. Has the diagnosis of metastatic brain tumor been confirmed by biopsy? If there was prior radiation, is there an increased risk of side-effects with this modality?

Stereotactic radiosurgery requires minimal hospitalization. There is no risk of infection, and it requires only a short period of time for recuperation. However, the results of treatment are not immediate and there is some risk of damage due to the radiation.

Stereotactic radiosurgery does not offer the opportunity for confirmation of the diagnosis.

Stereotactic radiosurgery may be useful as a boost to other forms of radiation therapy for metastatic brain tumors. The characteristics of those tumors appear to be ideal for that type of focused treatment. Investigational studies are still ongoing since radiosurgery has been used for metastatic brain tumors for only a few years.

INTERSTITIAL RADIATION THERAPY Interstitial radiation therapy is accomplished by surgically implanting radioactive seeds (sources of radiation energy) directly into a tumor. This technique delivers a large dose of radiation while reducing the effect on normal tissue. Small tumors less than five centimeters, about 2 inches in diameter that are surgically accessible may be considered for this treatment. Since surgery is required, only single tumors can be treated with this technique.

Interstitial radiation therapy may be beneficial to patients with radioresistant brain tumors such as metastatic melanoma, since larger doses of radiation can be delivered. It can be used with patients who have been treated with external radiation previously. However, this technique is a local therapy and does not address possible undetected cancer cells elsewhere in the brain. A second surgery may be required later to remove the mass of dead tumor cells.

DIFFERING SCHEDULES AND DOSAGES OF RADIATION THERAPY

Hyperfractionation

This is more than one radiation treatment per day, of traditional portions, usually with higher total doses.

Rapid fractionation

This is larger portions delivered over fewer days, usually with traditional total dosage.

Surgery

In general, surgery (resection) is recommended if the patient's general health is good, the primary cancer is under control, there are no systemic metastases, and there is a single, accessible tumor. Although metastatic brain tumors are malignant, they usually have well-defined margins and often can be totally removed if favorably located. Surgery is rarely recommended to lymphoma patients, because metastases from this cancer are extremely sensitive to radiation. Resection followed by whole-brain irradiation is recommended to approximately twenty-five percent of people with brain metastases. The remaining seventy-five percent are treated only with radiation therapy.

Other types of surgery are:

Biopsy to confirm the exact nature of the tumor, or to help diagnose the primary cancer if not yet determined.

Placement of a chemotherapy delivery device such as an Ommaya reservoir

Interstitial radiation therapy

Surgery for spinal metastases may be advised. The surgery involves resecting the affected vertebra (laminectomy). Indications for surgery include partial paralysis due to compression of the spinal cord, previous spinal irradiation, and patients with undiagnosed primary cancer.

Chemotherapy

Chemotherapy is recommended for spinal fluid metastases, but is still under investigation for use against metastatic brain tumors. The chemotherapy given is that which is effective against the primary cancer.

METASTATIC BRAIN TUMORS

Generally, chemotherapy that does not pass the blood brain barrier is of no value in the treatment of metastatic brain tumors. The blood brain barrier is a natural protective mechanism that restricts the entry of substances into the brain. There have been a few studies that demonstrated the effectiveness of some drugs. Some forms of chemotherapy can be effective against metastatic brain tumors from breast cancer including cyclophosphamide, 5-FU, and methotrexate. Tamoxifen may also be effective.

Currently, clinical trials are testing a variety of drugs. Intra-arterial chemotherapy is being tested for the treatment of lung cancer metastases to the brain. Manipulating the blood brain barrier so that drugs can enter the brain is also being studied. The ultimate role of chemotherapy, alone or in addition to radiation and surgery, remains to be determined.

SPINAL FLUID METASTASIS

The standard treatment for spinal fluid metastases is intraventricular [Intraventricular is drug delivery into a ventricle in the brain. An Ommaya reservoir is often used to insert the drug.] or intrathecal chemotherapy with methotrexate or cytarabine during and following radiation therapy. Thiotepa may be used with patients who do not respond to the above agents. Intrathecal chemotherapy consisting of methotrexate or thiotepa is especially effective against spinal fluid metastases from breast cancer. Cytosine arabinoside has also been used for breast metastases. Additional drugs are under clinical investigation cytarabine,

mercaptopurine, and diaziquone alone and in combination with methotrexate, in varying dosages.

METASTATIC SPINAL TUMORS

Treatment for spinal metastases consists of chemotherapy and radiation therapy. In addition, surgery or hormone therapy may be advised for some patients. The choice of drugs depends on the primary cancer. Hormone therapy may help patients with breast or prostate cancers.

Spinal metastases are not uncommon in women with breast cancer. Chemotherapy is given to women with bone pain who have no indication of spinal cord compression. Radiation therapy may follow if the chemotherapy is not effective or if spinal cord compression is present. Surgery also may be advised.

Hormone therapy

If the primary tumor is hormone-dependent, hormones or hormone-blocking agents may be prescribed. Breast cancers that are estrogen-receptor positive are treated with tamoxifen, which may also shrink the metastatic tumors. Prostate cancer metastases may also be affected by hormones. Steroids may act as hormones in patients with lymphoma.

Immunotherapy

Immunotherapy is a treatment that uses the body's natural defense mechanism the immune system. The goal is to stimulate the immune system so that it can effectively fight the cancer. Immunotherapy uses immune cells or substances called biological response modifiers (BRMs). BRMs either kill tumor cells directly, or stimulate the immune system to produce substances on its own to restrict tumor growth. BRMs can by produced by the body or manufactured in the laboratory. A number of investigational studies are underway using BRMs to treat spinal fluid metastasis.

Recurrent central nervous system metastases

Re-irradiation may be considered for recurrent central nervous system metastases. A second surgery is also possible for some patients. Chemotherapy for that condition is under

investigation.

6. COMMON CENTRAL NERVOUS SYSTEM METASTASES BY PRIMARY CANCER

Breast cancer

Often, metastatic brain tumors are multiple. There is a long interval between the time the breast cancer is initially diagnosed and the onset of central nervous system metastases. Few women have CNS metastases at the time of their initial diagnosis.

Twenty to twenty-five percent of women with breast cancer may develop central nervous system metastases. Those metastases may occur as brain tumors, spinal tumors, or spinal fluid metastases. Usually, they are associated with extensive edema.

Some women with breast cancer may have a type of benign primary brain tumor called meningioma rather than a metastatic brain tumor. If that is suspected on the basis of a brain scan, surgery often will be recommended to remove the tumor.

Colon cancer (and cancer of the rectum) A single brain tumor is more common than multiple tumors. There is a long interval between the time of initial colon cancer diagnosis and the diagnosis of central nervous system metastases.

Leukemia

Spinal fluid metastasis is more common with acute lymphocytic leukemia (ALL) than acute non-lymphocytic leukemia (ANLL); and more common in children than adults. Approximately five percent of people with ANLL may develop meningeal metastases. Fifteen percent of adults with ALL and up to fifty percent of children with ALL may develop spinal fluid metastases. A diagnostic lumbar puncture is done to obtain a sample of spinal fluid for diagnosis. Prophylactic irradiation [Prophylactic irradiation is radiation therapy administered to prevent the occurrence of metastases. Because of the high incidence of non-detectable leukemia cells in the spinal fluid, prophylaxis is administered to prevent meningeal carcinomatosis.] may be recommended for some children with ALL. The incidence of spinal fluid metastases in children drops to five percent with prophylaxis. The usual recommended prophylactic dose is 1800 cGy.

Headache is the most common symptom of spinal fluid metastasis, and is due to increased intracranial pressure. Cranial nerve paralysis may occur suddenly in a person with ALL, indicating metastasis. The sixth (VI) cranial nerve (the nerve that controls eye movement) and seventh (VII) cranial nerve (the nerve that controls facial movements) are most often affected. Immediate irradiation to the affected area is necessary to preserve use of the nerve.

Lung cancer

Adenocarcinoma

Multiple metastatic brain tumors are more common than single ones. Spinal and meningeal metastases are rare.

Squamous Cell

Fifteen percent of people with squamous cell lung cancer may develop brain metastases. Multiple tumors are more common than single ones. Spinal and meningeal metastases are rare.

Small Cell

Ten percent of people diagnosed with small cell lung cancer have brain metastases at the time of their initial diagnosis. Another twenty to twenty-five percent may develop that form of metastasis later. In general, the interval between initial diagnosis of small cell lung cancer and the diagnosis of central nervous system metastases is short. The likelihood of developing brain metastases increases with time. They may occur in as many as fifty to eighty percent of people after two years. Single brain tumors are more common than multiple tumors.

People with brain metastases are at increased risk to develop spinal and meningeal involvement. Less than two percent of people will have spinal metastases and less than one-half of one percent will have meningeal involvement at the time of initial diagnosis. Five percent of patients may develop metastatic spinal tumors and two and one-half percent may develop spinal fluid metastases.

Prophylactic radiation therapy is recommended only for patients in systemic remission. When radiation is administered, it will generally not be given on the same days as chemotherapy, and the time period between drug and radiation treatment should be as long as possible.

Lymphoma

Spinal tumors and spinal fluid metastases are the most common forms of central nervous system involvement; lymphomas rarely spread to the brain. Two percent of patients may experience spinal cord compression. The incidence of central nervous system metastases is low in Hodgkin's and low-grade non-Hodgkin's lymphomas. Nine to eighteen percent of people with higher grades of lymphoma may experience that form of metastasis. Prophylactic radiation therapy is advised for some forms of lymphoma.

The incidence of central nervous system metastasis of lymphoma is increasing because the incidence of that form of cancer is increasing.

Melanoma

More than fifty percent of patients with melanoma develop brain metastases; that type of cancer has the highest brain metastasis incidence rate. Spinal fluid metastasis is also common, often in addition to brain metastases. Metastatic spinal tumors are rare. The interval between initial diagnosis and central nervous system involvement may be long; people with melanoma should see their doctors regularly for follow-up exams. Metastatic brain tumors are most frequently multiple in number (about seventy-five percent of the time), and are associated with a high incidence of seizures (twenty-five to thirty-seven percent of people).

Renal (kidney) cancer Renal metastatic brain tumors are usually single in number.

7. WHAT YOU CAN DO TO HELP YOURSELF

Further reading

You may find it is easier to cope with your illness when you understand the reasons for the doctor's

recommendations, know in advance what to expect, know what symptoms to look for and what to do should they occur. Or, you may want to be assured you are receiving state-of-the-art treatment, and that no possible option has been overlooked. Or you may want to explore investigational treatments. For all those reasons, you may want to read more about your illness.

To obtain a copy of the publications, contact the ABTA. Other organizations that provide information are:

• The Leukemia Society of America Chicago, IL (312) 726-0003
• The American Lung Association. Check your local phone book.
• The American Cancer Society. Check your local phone book.
• Cancer Information Service offices throughout the country can provide you with current information on investigational treatments for your cancer and its metastases. Their telephone number is: (800) 4-CANCER.

Support groups

We maintain a computerized list of brain tumor support groups and clearinghouses. Call us at (800) 886-2282, or if you are in the Chicago area at (847) 827-9910, for a list of groups in your area.

Other support group information is available. Breast cancer patients can contact the local chapter of Y-ME, or their headquarters in Homewood, IL at (800) 221-2141 or (847) 799-8228 (24 hours).

The American Cancer Society sponsors I CAN COPE groups and offers a variety of services. Refer to your telephone directory for the number of the local chapter, or contact their headquarters in Atlanta, Georgia at (800) 227-2345 or (404) 320-3333.

The National Coalition for Cancer Survivorship in Silver Spring, Maryland, (301) 585-2616 is a clearinghouse for information and can direct you to local support groups. The NCCS has prepared a sourcebook: An Almanac of Practical Resources for Cancer Survivors. It is available at your local library, or can be purchased from Consumer Reports Books, Fairfield, Ohio, (513) 860-1178.

Other Resources

The social worker at your hospital can be an excellent resource for services.

The yellow pages of your telephone directory is also a good potential resource. Under the heading Social Service Agencies are many helpful listings.

We may be able to advise you of other agencies that meet your needs. Call us at (800) 886-2282, or if you are in the Chicago area, at (847) 827-9910.

8. CANCER STATISTICS

American Cancer Society, CA-A Cancer Journal for Clinicians, Jan/Feb 1992, Vol. 42, No. 1. Adapted with permission.

According to the American Cancer Society, the estimated number of new cancer cases in the United States, for selected sites, for 1992 was:

Site Total Number of New Cases

All sites 1,130,000

Breast 181,000

Colon-Rectum 156,000

Leukemia 28,200

Lung (all types) 168,000

Lymphoma (all types) 48,400

Melanoma 32,000

Prostate 132,000

Renal (kidney) 26,500

GLOSSARY

accessible

Refers to tumors that can be approached by a surgical procedure without causing undue neurological damage; tumors that are not deep in the brain or beneath vital structures.

arachnoid

One of the three layers of the meninges.

See meninges.

ataxia

A clumsy, uncoordinated walk often associated with balance problems.

benign

Not malignant, not cancerous, slow-growing.

biopsy (open or needle)

Biopsy is the process of removing a sample of tumor tissue to establish an exact diagnosis. The tumor sample is obtained during a surgical procedure and then examined under a microscope in the laboratory. Biopsies may either be open or needle and often are performed using stereotactic techniques.

blood brain barrier

A protective barrier formed by the linings of the blood vessels of the brain. It prevents some substances in the blood from entering brain tissue

carcinomatous meningitis See meningeal carcinomatosis.

catheter

A flexible piece of tubing used in body cavities to insert or remove fluid.

central nervous system

The brain, cranial nerves and spinal cord. The spinal cord is an extension of the brain.

cGy

centiGray. The standard of measurement of ionizing radiation.

contrast enhancement See MRI scan.

cranial nerves

Twelve pairs of nerves originating in the

brain.

CSF Cerebral spinal fluid. See spinal fluid in this glossary.

CT scan

Computerized Tomography. An x-ray device linked to a computer that produces an image of a predetermined cross-section of the brain.

dura mater

See meninges.

dysphasia

The impairment or loss of the ability to speak or write, to understand speech or written words. Dysphasia may be moderate or severe.

edema

Swelling due to excess water.

extra-dural

Outside the dura mater. Between the skull or spine and the dura mater. See meninges.

focal

Local; the opposite of widespread.

hemiparesis

Muscle weakness on one side of the body.

herniation

Bulging of tissue through an opening in a membrane, muscle or bone.

hydrocephalus

Excess water in the brain due to the blockage of spinal fluid pathways.

increased intracranial

Increased pressure within the skull. Caused by pressure mass effect.

intra-arterial

Within an artery.

intrathecal

Within the subarachnoid space of the meninges.

intravenous

Within a vein.

intraventricular

Within a ventricle in the brain. Drugs are often delivered intraventricularly using an Ommaya reservoir.

irradiation

Radiation therapy.

leptomeninges

Refers to the arachnoid and pia mater membranes of the meninges.

lesion

Tumor. May also refer to a wound or injury.

lumbar puncture

Also called a spinal tap. The insertion of a hollow needle into the subarachnoid space of the spine to withdraw a sample of spinal fluid for examination in the laboratory.

lymph

A fluid collected throughout the body. It flows through the lymphatic system and

eventually ends up in the veins.

malignant

Cancerous.

mass effect

An effect caused by blockage of spinal fluid, space taken up by a growing tumor, swelling or edema. May result in increased intracranial pressure, herniation.

median

Middle value. Equal quantities appear on either side of the middle value.

meningeal carcinomatosis

The widespread presence of cancer cells in the spinal fluid. An older term for

this condition is lepto meningeal metastasis. Another term used is carcinomatous meningitis.

meningeal lymphomatosis

The widespread presence of lymphoma cells in the spinal fluid.

meninges

The meninges are thin layers of tissue that completely cover the brain and spinal cord. The three layers of meninges are the dura mater, the arachnoid, and the pia mater. Spinal fluid flows in the space between the arachnoid and the pia mater. This is called the subarachnoid space.

metastasis

The spread of cancer cells from one part of the body to another. Metastatic tumors are tumors that arise at sites distant from the original location. Metastasis is singular; metastases is plural.

modality

Treatment method: surgery; irradiation; hormone therapy; chemotherapy; immunotherapy; etc.

MRI scan

MRI is Magnetic Resonance Imaging. MRI is a scanning device that uses a magnetic field, radio waves and a computer. Signals emitted by normal and diseased tissue during the scan

are assembled into an image.

Contrast enhancement is the use of an agent such as Gadolinium-DTPA, administered shortly before the MRI is performed, to enhance the images obtained so that tumors are more readily detected and their characteristics are more obvious.

myelography

A specialized x-ray technique. A radio-opaque substance injected into the subarachnoid space is followed by x-rays.

Ommaya reservoir

A device with a fluid reservoir implanted under the scalp with a catheter to a ventricle. It allows for medication to be given directly into the spinal fluid. See intraventricular.

palliation

Reduction of symptoms, relief.

papilledema

Swelling of the optic nerve, due to increased intracranial pressure.

parenchyma

The brain itself. Excludes the meninges

and spinal fluid.

pia mater

See meninges.

primary brain tumor

A tumor that originates in the brain; metastatic brain tumors originate elsewhere in the body.

prophylactic

Radiation therapy administered to prevent occurrence irradiation rather than to treat that which has already occurred.

radioresistant

Tumors that do not respond well to conventional radiation therapy.

radiosensitive

Tumors that respond positively to conventional radiation therapy the tumors shrink.

renal

Referring to the kidney, part of the

urinary system.

resect

Remove by surgery.

seizure

Convulsions. Due to the temporary disruption in electrical activity of the brain.

signs and symptoms

Signs are what the doctor can observe, either directly or as the result of various tests; symptoms are the sensations and feelings the patient describes.

spinal fluid

The liquid that flows between the layers of the meninges. It circulates around the brain and spinal cord.

spinal tap

See lumbar puncture.

stereotactic

Precise positioning in three dimensional space. Refers to surgery or radiation therapy directed by various scanning devices.

subarachnoid

See meninges.

systemic

Has an effect on the entire body, not just one

organ or system.

ventricle

A hollow space. There are four connected ventricles in the brain. Inside each ventricle are structures that form spinal fluid. Spinal fluid flows from and through the ventricles and the subarachnoid space surrounding the brain and spinal cord.

vertebrae

Bones of the spine. A single bone is a vertebra.

ACKNOWLEDGMENTS

We gratefully acknowledge the volunteer efforts of Gail Segal for the research and writing of this publication. We also extend our appreciation to Raymond Sawaya, M.D., Professor and Chairman, Department of Neurosurgery, U.T.M.D. Anderson Cancer Center, Houston, Texas for technical review.

A WORD ABOUT ABTA

The American Brain Tumor Association is a national, non-profit organization dedicated and committed to funding brain tumor research, providing patient services, and educating people about brain tumors.

This publication is but one in the library of booklets and pamphlets we write and distribute as part of our patient services program. If you find this publication helpful, help us to continue our fight against brain tumors. Your financial support is necessary. Please give as generously as you can we need each other

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To learn more about American Brain Tumor Association, contact the office at 847-827-9910, or the Patient and Family Line: (800) 886-2282, or by email: info@abta.org.