Metastatic Tumors to the Brain and Spine

American Brain Tumor Association
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Des Plaines, Illinois 60018
(708) 827-9910
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Typesetting of this publication was made possible in part by a grant from Elekta Instruments, Inc.

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

All rights reserved.
Copyright 1993
by American Brain Tumor Association
ISBN: 0-944093-26-4

Reproduction without prior written
permission is prohibited.

Explanations or discussion of terms
followed by an * or ** are printed at
the bottom of each page throughout this booklet.


HOW TO USE THIS BOOKLET
We urge you to read the Introduction on page 3 and Chapters one through five
beginning on page 5. 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. If the technical
information requires more than a word or two, the explanation is printed at the
bottom of the page.

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

The index contains all references to
primary cancer sites. In addition, the
index lists topics discussed in this
booklet.

To obtain copies of our printed
publications, or to request any of our
patient services, please complete the
request form on pages 57-58.


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.

Spinal tumors are diagnosed using spinal x-rays, bone scans, and MRI scans.
Myelography is required if surgery is
planned.


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.

We offer a wide variety of
publications to provide you with
explanations about the brain and its
functions, the effect of tumors on the
brain, and the various modalities used
to treat central nervous system
metastases. They include:

A Primer of Brain Tumors, A
Patient's Reference Manual

Dictionary for Brain Tumor Patients

Coping With a Brain Tumor

Living With a Brain Tumor, a
Bibliography

Chemotherapy of Brain Tumors

Immunotherapy of Brain Tumors

Radiation Therapy of Brain Tumors
Part I: A Basic Guide

Radiation Therapy of Brain Tumors
Part II: Background and Research Guide

Using a Medical Library

To obtain a copy of the publications,
see the request form on pages 57-58.
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 (708)
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 (708) 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 (708) 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

9. ILLUSTRATIONS

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.