Michael has three grade 3 brain tumors. Two on the right side and a smaller one on the left. These are aggressive tumors. They did not do surgery because of the size of the mass and he is doing radiation and chemotherapy. On the following page is an explanation of this type of tumor by Dr. John Henson of the Massachusetts General Hospital.

Glioblastoma Multiforme
and
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma

A Guide For Patients

John W. Henson, M.D.
MGH Brain Tumor Center
Cox 315
(617) 724-8770
http://brain.mgh.harvard.edu/

Copyright © John W. Henson

High-grade Gliomas

Anaplastic astrocytoma = Grade 3 astrocytoma
Glioblastoma multiforme = Grade 4 astrocytoma
Anaplastic oligodendroglioma = Grade 3 oligodendroglioma (oligodendrocytoma)
Anaplastic oligoastrocytoma = Grade 3 oligoastrocytoma = Anaplastic mixed glioma

Common Algorithm for Diagnosis and Treatment of High-grade Gliomas

Biopsy/Surgery Radiation Therapy Chemotherapy Observation

Astrocytomas 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.

High-grade gliomas are diagnosed by a biopsy

Once 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 dictate treatment, and also give important information about prognosis.

When neuropathologists analyze tumor tissue under a microscope, there are two main questions being asked:

First, what type of brain cell did the tumor arise from? The answer to this question gives the tumor a name, for example, astrocytoma.
Second, do the tumor cells show signs of rapid growth? This involves assigning the tumor a grade, such as grade 3 or 4 (see below).

These 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.

Tumor name: what type of brain cell did the tumor arise from?

Astrocytomas 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.

Tumor grade: how aggressive does the tumor appear under the microscope?

Astrocytomas 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.

Gliomas have more than one name in everyday usage. The list on the following page gives the common names of high-grade gliomas.

Types of therapy

Because 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 following page.

There 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 treatments.

While therapies for high-grade gliomas are helpful, at present these treatments cannot cure the 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 most glioma cells are at least partially resistant to radiation and chemotherapy.

The goals of treatment are, therefore:

to remove as many tumor cells as possible (with surgery)
to kill as many as possible of the cells left behind (with radiation and chemotherapy)
to put remaining tumor cells into a nondividing, sleeping state for as long as possible (with radiation and chemotherapy)

High-grade glioma cells almost always start to grow again. 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.

Surgery

The 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.

There 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 patient’s 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.

With 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 full-scale surgery.

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.

An MRI scan is usually obtained within 3 days after tumor removal. This “post-op” MRI serves as a baseline for future comparison.

Radiation therapy

Radiation therapy is an important part of the treatment of high-grade gliomas. In standard therapy situations, patients begin radiation treatments within 2 to 4 weeks after tumor resection. A physician who supervises radiation treatments is called a radiation oncologist.

Following 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).

There 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 patients, 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 one that can produce major health problems. Fortunately, serious side effects are rare. 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 therapy.

An 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.

Chemotherapy

Chemotherapy 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. Whereas for most tumors radiation is given prior to consideration of chemotherapy, chemotherapy is often administered prior to radiation therapy for patients with anaplastic oligodendrogliomas.

Chemotherapy 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 may 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.

In 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.

The 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 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 the cells 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.

Two 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.

Women 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 chemotherapy.

When 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.

After treatment is completed

Once 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 an MRI or CT is obtained.

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