multiforme and anaplastic gliomas:
A patient guide
by John W. Henson, M.D., MGH Brain Tumor Center
and oligodendrogliomas are the most common primary tumors
of the adult brain. Both tumors are types of gliomas.
Primary brain tumors arise from cells of the brain itself
rather than traveling, or metastasizing, to the brain
from another location in the body. Gliomas can be slowly
growing (low-grade, grades 1 and 2), or rapidly growing
(high-grade, grades 3 and 4). This material will give
important facts about the diagnosis and treatment of high-grade
gliomas are diagnosed by a biopsy
a brain tumor is detected on a CT or MRI scan, a neurosurgeon
obtains tumor tissue for examination by a neuropathologist
(a biopsy). The neuropathologist then gives the tumor
a name and grade. The exact name and grade of the tumor
determine treatment options, and also give important information
neuropathologists analyze tumor tissue under a microscope,
there are two main questions being asked:
what type of brain cell did the tumor arise from? The
answer to this question gives the tumor a name, for
do the tumor cells show signs of rapid growth? This
involves assigning the tumor a grade, such as grade
3 or 4 (see below).
two pieces of information are then combined, as in "grade
4 astrocytoma". Once a tumor has been given a name
and a grade, brain tumor specialists can give advice about
treatment choices, prognosis, and provide useful health-care
information to brain tumor patients and their families.
name: from what type of brain cell did the tumor arise?
arise from brain cells called astrocytes. Normal astrocytes
are star-shaped cells that give the brain its shape. Astrocytes
are the most common cell type to become tumors. Oligodendrocytes
are brain cells that provide insulation around the electrically-active
neurons. Tumors of oligodendrocytes are less common than
astrocytomas. Many tumors contain a mixture of astrocytoma
and oligodendroglioma cells. Tumors of other cell types
in the brain are less common. For instance, tumors of
neurons are very rare in adults.
grade: how aggressive does the tumor appear under the
and oligodendrogliomas come in four grades, with grade
1 being the most benign and grade 4 being the most malignant.
The neuropathologist looks at the brain tumor tissue under
the microscope for signs that the tumor is growing rapidly.
Examples of these features include cells undergoing division
(mitosis), the presence of newly-formed blood vessels,
and evidence that the tumor is outgrowing its blood supply
(necrosis). The more features that are present, the higher
the grade assigned to the tumor.
have more than one name in everyday usage. The Table gives
the common names of high-grade gliomas:
for high-grade Gliomas
astrocytoma = grade 3 astrocytoma
multiforme = grade 4 astrocytoma
oligodendroglioma = grade 3 oligodendroglioma (oligodendrocytoma)
oligoastrocytoma = grade 3 oligoastrocytoma = anaplastic
do brain tumors occur?
form because of the abnormal, unregulated growth of cells.
After the human brain completes it development soon after
birth, the vast majority of its cells enter a resting
state in which they never divide again. One exception
to this rule is when a brain tumor develops. The abnormal
brain cells re-enter the "cell-cycle" because
of alterations in any of a large number of genes that
control cell division and growth. Although much is known
about the alterations in these genes in brain tumors,
the reason why the gene alterations arise in the first
place is poorly understood. The MGH has a very active
research program in this area.
brain tumors hereditary?
use of the word gene invariably brings up
the important question of whether brain tumors are hereditary.
The answer for almost all patients is no. Although there
are conditions in which brain tumors can occur in families,
these syndromes are very rare and usually known prior
to the development of an individual family members
tumor. Syndromes that include an inherited risk of glial
brain tumors include neurofibromatosis type I, Turcots
syndrome, and Li-Fraumeni syndrome.
are three standard types of treatment for patients with
high-grade gliomas: surgery, radiation therapy, and chemotherapy.
In addition to these standard therapies, major centers
such as the MGH Brain Tumor Center may offer experimental
grade 3 and 4 tumors have a tendency to grow rapidly,
treatment must be started as soon after surgery as is
feasible, allowing time for the surgical incision to heal.
Generally, this means that patients should be undergoing
either radiation therapy or chemotherapy within 2 to 4
weeks after surgery. An algorithm that is commonly used
for treatment of high-grade gliomas is presented on the
therapies for high-grade gliomas are helpful, at present
these treatments cannot cure these tumors. The two major
reasons for this are that tumor cells infiltrate into
surrounding brain and thus cannot be completely removed
by the surgeon, and that most glioma cells are at least
partially resistant to radiation and chemotherapy.
goals of treatment are to:
as many tumor cells as possible (with surgery)
as many as possible of the cells left behind (with radiation
remaining tumor cells into a nondividing, sleeping state
for as long as possible (with radiation and chemotherapy)
glioma cells almost always start to grow again at some
point in time. Patients receive aggressive treatment in
order to delay this regrowth as long as possible. Regrowth
does not necessarily imply loss of control of the tumor,
but it does mean that a new series of treatments should
be considered because the tumor is becoming more aggressive.
first step in therapy is maximal feasible removal of tumor
tissue. Surgeons believe that patients with smaller amounts
of tumor when they start other treatments will have a
better prognosis. Also, radiation therapy is more easily
tolerated when the pressure from the tumor can be reduced.
is great variability in the amount of tumor that can be
safely removed from the brain of a patient. The variability
is based mainly on the location of the tumor. For instance,
tumors in some brain areas can be removed with very low
risk, while in other brain areas surgery is too risky
to contemplate. The decision about the benefit and risk
of surgical removal is one that experienced brain tumor
neurosurgeons make every day. The underlying principle
is that the surgery should not worsen the patients
condition. The goal is for the patient to be the same
or better after recovering from brain tumor removal. When
a tumor is located in a sensitive area of the brain, a
biopsy is performed with a small needle, thereby avoiding
further damage to brain function. It is important to remember
that gliomas infiltrate into surrounding brain, making
complete removal impossible in almost every case.
modern neuro-imaging techniques such as MRI scans, it
is possible for doctors to have a high level of confidence
that a brain tumor is present prior to biopsy. In that
case, it is safe to perform a major surgical resection
at the same time as obtaining tumor tissue for the pathologist
to examine. In some cases, however, it is necessary to
perform a needle biopsy first, and later proceed to a
preliminary diagnosis ("frozen section diagnosis")
is made by the neuropathologist during the surgery in
order to help the neurosurgeon know what type of tumor
is present. The patient and their family are informed
of this preliminary diagnosis immediately after surgery.
However, further recommendations about treatment are not
made until the final pathology report is available. The
final report requires a minimum of 2 working days after
surgery. In difficult cases, the final report can take
a week. It is not uncommon for small, but important, changes
to be made in the diagnosis once all of the biopsy sections
have been examined.
MRI scan is usually obtained within 3 days after tumor
removal. This "post-op" MRI serves as a baseline
for future comparison.
therapy is an important part of the treatment of high-grade
gliomas. In typical situations, patients begin radiation
treatments within 2 to 4 weeks after tumor resection.
A physician who supervises radiation treatments is called
a radiation oncologist.
a "simulation" session in which the radiation
oncologist plans the shape of the radiation beam as well
as dose, treatments are given daily, Monday through Friday,
for 4 to 6 weeks. Each treatment takes only a few minutes.
During radiation, patients are seen weekly by the radiation
oncologist, and a nurse is available for questions every
day. Most patients feel better during radiation therapy
if they are taking a small dose of a steroid which reduces
brain swelling, called Decadron (also called dexamethasone).
are usually no immediate side effects during each treatment.
As the treatment progresses, hair loss will occur over
the area where the radiation beam passes into the tumor.
Most patients experience some fatigue by the second or
third week. For many, a 30 minute nap is helpful every
afternoon. There are a number of long-term side effects
from radiation therapy, ranging from those that are a
minor nuisance to ones that can produce major health problems.
Fortunately, serious side effects are rare. Furthermore,
the potential risks of radiation therapy are outweighed
by the known risk of not treating the tumor. The radiation
oncologist will describe these risks prior to starting
MRI is usually obtained about 2 to 4 weeks after the end
of radiation therapy in order to judge the effect of treatment.
Most of the time this scan will show no change from the
post-operative MRI, which is good. Some shrinkage is even
better. Growth during radiation therapy is an unwanted
sign of an aggressive tumor.
is helpful in controlling the growth of high-grade gliomas.
Several different types of chemotherapy drugs are available.
A neuro-oncologist is skilled at recommending these treatments.
For most tumors radiation is given prior to consideration
of chemotherapy, however, chemotherapy is often administered
prior to radiation therapy for patients with anaplastic
for glioblastoma multiforme raises an important question
as to timing. Although chemotherapy is beneficial, it
is not known whether the timing of administration is important.
Many centers in the United States now save chemotherapy
until there is evidence that the tumor is growing after
radiation therapy. This may mean that months or even years
could elapse between radiation and chemotherapy. Other
specialists prefer to give chemotherapy immediately after
radiation therapy and to give different chemotherapy when
the tumor starts to grow again. This decision has to made
on a patient-by-patient basis.
addition to standard chemotherapy, there are studies of
new drugs which are conducted in major research centers.
It is usually good to enter a research study if eligible,
both for reasons of personal benefit and for the benefit
of others in the future. Neuro-oncologists will provide
information about clinical trials.
possible side effects of chemotherapy will be discussed
before beginning treatment. Today, chemotherapy is much
less toxic than even a few years ago. Although chemotherapy
is targeted against dividing tumor cells, there are normal
cells in the body which are also dividing. These normal
cells can also be temporarily affected by chemotherapy
and may lead to side effects. Specifically, the cells
which can be affected are those in the bone marrow and
the cells which line the gastrointestinal tract. The cells
in the bone marrow form the blood cells that are circulating
in the body. These cells include white blood cells which
fight infection, red blood cells which carry oxygen, and
platelets which prevent bleeding.
other types of cells which may be affected temporarily
or permanently are the female egg cells and those cells
which produce sperm in the man. In men, chemotherapy can
cause sterility, and therefore may make men unable to
father a child. Men should discuss this with the doctor
before starting chemotherapy.
of child-bearing years need to use a reliable birth control
method for the entire time, including the rest periods,
when receiving chemotherapy. Men should use a condom when
having sexual relations within 3 days of getting chemotherapy
to protect their spouses from exposure to the drug. The
effects of many chemotherapy drugs can be harmful to the
growth and development of a fetus, therefore it is crucial
to not become pregnant or father a child while receiving
receiving chemotherapy, and for 3 days after, it is important
that careful attention be paid to hand washing after urination.
Since many chemotherapy drugs are removed from the body
by the urine, careful hand washing will prevent family
members from being exposed to the chemotherapy. If family
members help with personal care of the patient, they should
wear rubber gloves when handling urine or vomitus. Clothing
soiled with urine, vomit, or feces should be washed separately
in hot soapy water.
treatment is completed
the recommended treatments have been completed, an observation
phase is entered. In the observation period, visits to
the neuro-oncologist occur every 2 to 4 months. At these
visits there is a review of symptoms, medications, physical
condition, and usually a surveillance MRI or CT is obtained.
and careful follow-up are necessary because of the harsh
reality that high-grade gliomas have a well-known tendency
to regrow. Most often, regrowth occurs at the same site
where the tumor arose. If and when tumor progression is
discovered, brain tumor specialists may recommend further
surgery, radiation, or chemotherapy.
prognosis is different for each of the tumors discussed
in this booklet. The specialists will discuss prognosis
the hospital after surgery
patients recover very quickly after surgery on their brain
tumor. The majority are able to leave the hospital within
a few days. Some patients go directly home, whereas others
benefit from inpatient stay in a rehabilitation hospital
to optimize physical function and to gain strength prior
to going home. The neuro-surgeon will remove the sutures
7 - 14 days after surgery. The head should be kept dry
until the sutures have been removed.
the last page of the booklet, there is a check list to
complete before leaving the hospital. It is important
to meet the doctors who will be part of the team of brain
tumor specialists. There are three kinds of brain tumor
it is not possible to see all three specialists in the
hospital, in which case their names, telephone numbers,
and an appointment date will be provided prior to discharge.
Also plan to see a primary care doctor soon after discharge.
This doctor will be an important resource for general
medical problems, should they arise.
permanent notes in a notebook
will be many discussions with doctors and nurses about
symptoms, test results, treatments, and medications. It
is helpful to keep careful notes and dates in a permanent
book like a college notebook or a diary.
of common medications
Decadron (dexamethasone) is very useful to reduce swelling
around the tumor. It also has many side effects, but these
are usually less important that the benefit from taking
Decadron. However, it is always a major goal find the
smallest dose that is helpful. Side effects include: euphoria,
with excessive feeling of well-being and insomnia; increased
appetite, especially for sweets; weight gain with fat
deposition in the cheeks; high blood sugar, particularly
in diabetics; high blood pressure; muscle weakness in
the legs (this affects climbing stairs and arising from
chairs); stomach ulcers (an acid blocking drug is usually
given to combat this); and increased risk of infection
(patients on Decadron for more than 2 months should ask
about prophylactic Bactrim). It is not necessary to check
blood levels of Decadron.
Dilantin (phenytoin) is a common medication taken to prevent
seizures. The major side effects of Dilantin are toxic
blood levels (too high), and rash. Dilantin toxicity causes
clumsiness while walking, much like that of alcohol intoxication.
Dilantin rashes are very common and can be dangerous so
that the patient must quickly switch to a different medication
for seizure control. (Note: changing a seizure medication
requires consultation with a neurologist or neuro-oncologist).
Some patients experience fatigue with Dilantin, but this
symptom is more commonly due to the tumor and its treatment.
Tegretol (carbamazepine) is a common anti-seizure medication.
It may cause a rash, may lower the white blood counts,
and often causes double vision when levels become toxic.
Depakote (valproic acid) is another common anti-seizure
medication. The most frequent side effect is a mild tremor
in the hands. The liver can be injured by this medication.
A rash is much rarer than with Dilantin. This medication
is very harmful to the human fetus and cannot be given
to pregnant women.
is important to identify and keep in touch with a primary
care doctor or family physician. Remember to ask each
specialist to send copies of all letters and notes to
the primary care doctor. The primary care doctor should
be contacted for many issues that will come up with general
health and insurance matters. For questions about surgery,
radiation, and chemotherapy, and medications for the tumor,
the specialists should be contacted by the primary care
doctor or by the patient and family.
to call the specialist
should call the specialist in the following situations:
a seizure (see below).
headache or abrupt worsening of existing neurological
of the ankles and legs, particularly if the swelling
is worse in one leg than in the other. This may indicate
the presence of a blood clot in the large veins of the
legs (this is called deep venous thrombosis, or DVT).
The risk of DVT is quite high in patients with brain
tumors. DVTs are dangerous because the clots can break
off and travel to the lungs. Blood thinner pills are
usually required after diagnosis of a DVT.
of infectionfever, chills, pain on urinating,
unusual headache, stiff neck, sore throat, or severe
of possible bleedingunusual bruising, severe headache,
unusual abdominal pain, bright red blood from the nose
nausea and vomiting.
are some of the situations in which a doctor needs to
be contacted. Sometimes it is hard to know whether to
call the doctor about a certain problem. If unsure, it
is safest to call. Telephone numbers of the doctor and
a number at which the doctor on call can be reached after
hours or on weekends should be kept available.
may occur in patients with brain tumors. Seizures can
have many different manifestations, but common types are
twitching of the face, arm or leg without complete loss
of consciousness, and total body shaking with complete
loss of consciousness.
seizures are brief and self-limited. If a seizure lasts
for 2 minutes or less and the patient returns to normal
quickly, make a telephone call to the neuro-oncologist
at the Brain Tumor Center (617-724-8770) for instructions
(for example, to check the blood level of a seizure medication).
If the seizure lasts for more than 3 minutes or if a second
seizure occurs, it is usually necessary to call for medical
help by dialing 911. Have the doctor at the Emergency
Room call the Brain Tumor Center for advice.
patients with seizures, the following activities should
be discussed with a neuro-oncologist: driving, operating
heavy equipment, swimming, any potentially dangerous activity.
the event of a seizure, four things are important:
not put anything in the patients mouth
the patient from sharp objects or dangerous situations
during the seizure
vomiting occurs, turn the patient on their side to minimize
the risk of aspiration
calm and call for help. Patients do not suffocate during
help at home
are some important things to do at home. These include:
a positive mental attitude.
medications faithfully and as prescribed. Pharmacies
sell pill organizers which can help as a memory aid
a written, up-to-date list of medications for review
at home or at the doctors office.
a healthy dietincluding plenty of fresh fruits,
fruit juices and vegetables to prevent constipation.
1 multivitamin with iron each day.
some form of exercise-- even a little is better than
none. However, avoid exhaustion.
change in usual sexual activity is necessary. Contraception
is very important.
alcohol. Some specialists allow patients to take small
amounts of alcohol on occasion, but since alcohol impairs
brain function and can worsen the side-effects of medications,
the safest policy is to stay away from it altogether.
alert to signs of infection or bleeding.
most patients who are working at the time their illness
strikes, a 3 - 6 month period of disability is a good
idea. It is usually difficult to have daily radiation
treatments while working, for example, and the stress
and fatigue produced by the illness and therapy require
plenty of rest. Because tumors in brain tissue often directly
effect mental ability or physical ability, many types
of work become simply too challenging or even impossible.
For patients who are significantly affected by their tumor,
permanent disability is often best. The patient and close
family members are usually best able to determine what
work will be practical.
admission to the MGH
surgery, if it becomes necessary to be admitted to the
MGH for treatment or for a complication, patients are
usually admitted to the Neuro-Oncology Service. This inpatient
service is under the leadership of the Brain Tumor Center
neuro-oncologists (the "attending"), who is
assisted by a neuro-oncology "fellow", neurology
residents, and specialist nurses. Physical and occup-ational
therapists usually help with exercises. A case manager
helps to make plans for discharge to home, rehabilitation,
or other location.
attending neuro-oncologist working on the inpatient service
upon admission may not be the patients primary neuro-oncologist,
since the hospital attendings rotate at the beginning
of each month. However, all major decisions will be made
in conjunction with the primary neuro-oncologists
advice. The primary neuro-oncologist will make frequent
visits to check on the overall progress during the hospitalization.
Fellows and Nurse Practitioners
MGH Brain Tumor Center has a training program for new
brain tumor specialists. These "fellows" are
fully-trained physicians who are specialists in neurology,
neurosurgery, or medical oncology, and who are taking
advanced education in neuro-oncology. The fellows will
be helpful with all aspects of treatment and follow-up.
Similarly, the MGH Brain Tumor Center has nurse practitioners
who work with the attendings and fellows to provide patients
with the best possible care.
Therapy and Rehabilitation
a hospital admission, a physical therapist may be consulted
to assess your functional status and provide treatment
aimed at maximizing your independence and functional capacity.
Upon discharge, home or out-patient physical therapy may
be recommended to continue to maximize your functional
mobility. If you require more intensive physical therapy,
you may benefit from an inpatient stay at a rehabilitation
hospital. Physical therapy evaluation includes identifying
what areas may be limiting your function: strength, balance,
endurance, pain. The physical therapist may prescribe
individualized exercises to address the above areas, and
may recommend adaptive equipment.
therapy (OT) is the therapeutic use of self care, work,
and leisure activities to increase independent function
and prevent disability. It includes adapting tasks and
the environment to maximize an individuals independence
and quality of life. An occupational therapist can assess
level of function in activities of daily living (ADLs),
taking into account physical, cognitive and perceptual
abilities as they influence performance of these tasks.
An occupational therapist can give instruction in the
use of assistive devices, adaptive techniques and hand
splints (as necessary) to increase independence in day-to-day
tasks. Occupational therapists evaluate and treat individuals
in the hospital unit, at home. The outpatient service
is located at ACC 127. Following a physician referral
for outpatient OT, call (617) 724-6575 to schedule an
social workers are licensed professionals trained to help
people find solutions to many emotional problems-- from
daily crises to life's most difficult situations. This
is accomplished through a unique combination of counseling,
active problem solving and direct connection with the
network of community and hospital resources. To speak
with a social worker, simply ask a nurse or physician,
or call the Social Service Department at (617) 726-2643
or (617) 726- 5841 (outpatient).
Cancer Resource Room (on the first floor of the Cox Building)
is an important resource at the MGH. It is a place where
patients and families can find information about everything
from treatment modalities to coping to talking with one's
children. Another helpful resource is the Brain Tumor
Support Group which meets in the Brain Tumor Center the
1st and 3rd Tuesdays of the month from 12:00-1:30 PM.
The group offers an opportunity for patients and family
members to learn about the issues that concern them most
as well as an opportunity to meet others living with similar
experiences. For more information call (617) 726-5841.
about brain tumors is available from home on the world
wide web. Here are some useful web sites to visit:
Tumor Center (617) 724-8770 http://brain.mgh.harvard.edu/
Tumor Society (800) 770-8287 http://www.tbts.org/
Brain Tumor Association (800) 886-2282 http://www.abta.org/
of the doctor to contact in case of an urgent question.
(Suggestions about when to call a specialist are presented
of medications, and prescriptions.
what to do in case of a seizure (see above).
to see a primary care doctor in the next two weeks.
1999 John W. Henson, M.D.