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The following is from the American Brain Tumor Association

(please note, it is basic information, for new breakthroughs on treatment- please see Constantine's thorough and complete up to the minute report on Brain Mets HERE.)



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.


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.

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.

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.

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.


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.

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.




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