What is a Glioblastoma?

There are many different types of malignant or cancerous brain tumors. In most cases, a brain tumor is named for the cell type of origin. The most common type of primary brain tumors are the gliomas. Gliomas arise from glial cells which are supportive cells that surround, nourish and protect neurons. One type of glioma is an astrocytoma. Astrocytomas are graded I through IV, depending on the degree of aggressiveness. The most aggressive astrocytoma, grade IV, is also called a glioblastoma (GBM). Of all brain tumors, a GBM has the greatest potential for rapid growth.

GBMs mainly arise in the cerebral hemispheres (the main portions of the brain), but they can also occur in the brain stem, cerebellum, or spinal cord. Symptoms of a GBM can include headaches that are caused by increased intracranial pressure (pressure inside the skull), memory loss, seizures, personality changes, and coordination difficulties. The spread of a GBM to other parts of the body is extremely rare.

Who gets Glioblastomas?

About one-fifth of all adult primary brain tumors are glioblastomas. GBMs are more common in men than in women, and older adults are at greater risk. The average age at diagnosis is 64. GBM is rare in children, comprising about 3% of all reported pediatric brain tumors.
At present, the exact cause of GBMs is unknown. Studies have examined previous radiation, electromagnetic fields, cell phones, chemicals, and family hereditary connections.

How is a GBM identified?

The main way of identifying a brain tumor is by the use of an MRI (magnetic resonance imaging) or a CT scan (computerized tomography) combined with an analysis of the brain tissue. Because of the distinct appearance of a GBM, the doctor is able to have a fairly good idea of the tumor type by examining the MRI scan. But for a definitive diagnosis, a sample of the tumor must be analyzed by a pathologist.

CT scanning provides successive X-ray views of thin sections of the brain. Contrast agents are given by injection before CT scanning to improve the read- ability of the scan.

MR Imaging (MRI) is a very precise and sensitive tool for evaluating tumors in the brain. Unlike CT scanning, an MRI does not rely on radiation, but makes use of magnetic field patterns with a contrast agent called gadolinium. For evaluating a brain tumor and follow-up, an MRI is generally the preferred method.

It is common to feel anxious before undergoing an MRI. Bring up concerns beforehand as the doctor may be able to prescribe medication to help relieve the symptoms of apprehension. Open MRI facilities may be available for claustrophobic patients, pediatric patients, larger patients, or for others unable to have a traditional MRI.

Gadolinium, the contrast agent used with an MRI, may cause a temporary headache. Tests to check kidney function may be performed prior to giving gadolinium. Because an MRI uses magnetic fields, it is important to let the doctor know if there is any metal implanted in the body.

Biopsies are used to obtain a sample of tissue from the tumor site. Safety and the location of the tumor deter- mine the most appropriate biopsy procedure. If a tumor is deemed to be operable, the sample is obtained at the same time as the surgery. If a tumor is difficult to access, a stereotactic (or needle) biopsy may be used. A pathologist examines the tissue under a microscope to classify the tumor type and its grade, which can range from grade I, which is benign to grade IV, which is malignant.

How are brain tumors treated?

Treatment for brain tumors depends on the type, size, and location of the tumor. Generally, standard treatment consists of a combination of surgery (when pos- sible), radiation therapy, and chemotherapy. The goal of surgery are to establish the diagnosis by removing a sample for the pathologist to examine, and to safely remove as much of the tumor as possible. While surgical removal is a mainstay of therapy, surgery alone cannot address the microscopic tumor cells which may have already spread through normal brain tissue by the time the tumor is discovered.

Radiation therapy and chemotherapy are usually used as secondary treatments to destroy tumor cells that cannot be removed by surgery or when surgery is not advised. Presently, the standard protocol involves radiation therapy five days a week for six weeks, in combination with a daily oral chemotherapy called temozolomide. In most cases, temozolomide is then administered on a monthly cycle of five days per month. The dosage and number of cycles is determined by the doctor. Regular blood draws will monitor the patient’s blood counts. Periodic MRIs will be used to monitor the tumor’s response to treatment.

The goal of treatment is to alleviate symptoms and to control the growth of any remaining tumor for as long as possible with the fewest possible side effects.

What is important to know about surgery?

There are several factors that determine whether a tumor is operable, including the location of the tumor, its proximity to vital structures, the extent of its invasiveness, and its relation to the blood supply within the brain.

Surgery is performed by a neurosurgeon. Except in cases of GBMs that cannot be treated surgically because of their location or the extent of their invasiveness, the neurosurgeon operates to remove as much of the tumor as possible. Depending on the location of the tumor, brain mapping may be used to help surgeons avoid critical brain structures when performing surgery near important areas, such as the speech or motor strips.

Technological advances in the operating room have resulted in greater precision in performing delicate operations. Surgical microscopes give neurosurgeons a clear view of even the smallest area of tissue and allow great precision in performing delicate operations. Navigational tools, such as interactive or “real-time” MRIs that record images during surgery, allow for on-screen monitoring during the operation and offer a greater chance of find- ing and removing the divergent areas of invasive GBMs. Research suggests that the more of the tumor that can be removed surgically, the better the prognosis.

The concept of brain surgery can certainly be frighten- ing. In some cases, surgery is urgent and must be per- formed as soon as possible. Talking with the doctor and asking questions beforehand can help to reduce anxiety. Ask about the risks and benefits and what to expect throughout recovery.

What is important to know about Radiation Therapy?

For patients who have already completed surgery, or in cases where surgery is not advised, treatment with radiation therapy and chemotherapy is recommended.

Radiation therapy is planned and overseen by a radiation oncologist. After reviewing the scans or images of the tumor area, the radiation oncologist works with the neurosurgeon to plan an appropriate course of radiation therapy. The radiation oncologist will also discuss possible benefits and side effects of the therapy with the patient.

The goal of radiation therapy is to destroy tumor cells without injuring normal brain cells around the margin of the tumor. Radiation relies on the theory that tumor cells are rapidly dividing, and therefore their DNA is sensitive and able to be damaged by the radiation. The body’s normal cells have a better capacity to repair this kind of damage after radiation.

Radiation treatment is typically given five days a week for six weeks. The radiation is usually focused to the area of the tumor and its immediate surroundings. Techniques for delivering the best radiation treatment will be evaluated by the radiation oncologist depending on the type of tumor and its location. Currently available techniques include conventional 2D coplanar treatment, 3D conformal treatment, intensity modulated therapy, and radiosurgery technique. The type and schedule for radiation will depend on what the patient and their radiation oncologist determine to be the most appropriate. Also, the total amount of recommended radiation varies with age.

Following surgery, radiation therapy is the single most effective treatment for GBM, and it is used as the primary treatment for cases in which surgery would involve too great a risk to the patient. Radiation therapy has resulted in better survival rates than either surgery alone or surgery plus chemotherapy.

Most patients receive oral chemotherapy, temozolomide, at the same time as radiation. Studies have shown improved survival when combining radiation with temozolomide as compared with radiation alone.

What is Chemotherapy?

After surgery and radiation therapy, chemotherapy may be overseen by a neuro-oncologist (cancer doctor who specializes in the treatment of brain tumors) or medical oncologist. Chemotherapy works to destroy remaining tumor cells with drugs given either alone or in combination with other treatments. Like radiation, chemotherapy is directed at rapidly dividing cells.

Chemotherapy is usually given by mouth or injected in a vein. It can also be administered directly to the tumor site through biodegradable polymer wafers saturated with chemotherapy that are placed directly inside the tumor cavity at the time of surgery. An important consideration to discuss with the treatment team is how the use of wafer implants may affect a patient’s future eligibility for clinical trials.
Some common chemotherapy drugs include Temodar® (temozolomide), BCNU (carmustine), and CCNU (lomustine). Many new chemotherapeutic agents are being studied in clinical trials to investigate their efficacy and safety.

The neuro oncologist or medical oncologist will work with the neurosurgeon, radiation oncologist, and the patient in order to plan an appropriate course of chemotherapy. Patients may choose to discuss participation in clinical trials as a possible treatment strategy. Open dialogue with the treatment team about the goals of treatment, the potential risks and benefits, and quality of life will help in choosing an appropriate treatment plan.

What are some side effects?

All treatments for brain tumors have the potential for side effects. Because chemotherapy and radiation can- not always be directed exclusively at the tumor, they can potentially damage healthy as well as diseased tissues.

Radiation therapy is generally done on an outpatient basis with daily treatments. Patients are usually able to function at a normal level throughout the treatment, although some people may notice increasing fatigue toward the end of the therapy. Radiation therapy may
cause patchy hair loss and a dry scalp, and in some rare cases, a slight worsening of neurological problems.

Chemotherapy may cause nausea and can be associated with fatigue, weight loss, skin changes, and increased risk of infection. Each drug has a particular profile of side effects that the oncologist will discuss with the patient. For instance, side effects of Temozolomide may include nausea, vomiting, headache, fatigue and constipation. Additionally, the side effects of Avastin® (bevacizumab) may include high blood pressure, protein leakage in the urine, strokes, blood clots, bleeding, and impairment of wound healing.

Fatigue is common following brain tumor treatment. The fatigue can be severe, and is often described as feelings of weakness, exhaustion, lack of energy, sleepiness, and confusion. Cancer fatigue may also affect how people think and make it hard to pay attention, read, or multi- task. Strategies, like taking short naps and identifying the time of day when energy levels are high, may help to cope with fatigue. The doctor or nurse may be able to suggest additional strategies to manage fatigue.

Changes in brain cognition, or function, may also occur after brain tumor treatment. This can include changes in concentration, memory, language skills or behavior. Receiving an evaluation by a neuropsychologist (a licensed psychologist specializing in brain-behavior) can help determine an appropriate treatment plan. Cognitive rehabilitation may include a variety of therapeutic activities and skill-based activities to assist with regaining brain function.
Currently, there are many drugs and therapies that can help alleviate the side effects of treatment. Patients should discuss with their doctors the different options for treating any side effects that arise.

What medications treat symptoms?

The two most common medications are steroids, to reduce swelling of the brain, and anticonvulsant medications, to prevent seizures. The doctor may also prescribe blood thinners for patients at risk for blood clots.

Steroids are given to reduce and control swelling of the brain, particularly before and after surgery. They do not kill tumor cells, but used alone or combined with other forms of treatment, they can bring about remarkable improvement in a patient’s condition simply because of rapid control of cerebral edema (brain swelling).

When used for only a few days, steroids generally cause minimal side effects, including flushing of the face, mild fluid retention, swelling of the hands, feet, or face, and an increase in appetite. Used over a long period of time, however, steroids may produce physical and mental reactions such as a change in the patient’s body, including swelling of the face, arms, and legs, possible mood swings, acne, and softening of the bones. Other effects include decreased strength in the patient’s legs, more fragile skin, increased potential for sugar diabetes, and water and fat weight gain. These side effects usually disappear when the drug is carefully discontinued.

It is very important that a doctor carefully supervises the discontinuation of steroids. Steroids are usually tapered off, or reduced gradually, even if they are caus- ing unpleasant side effects. Abrupt discontinuation of these drugs can cause severe problems. The body needs to slowly adjust so that it can start natural production of steroids again.

Anti-seizure medications

To help protect patients from having seizures, and possibly even keep them free from seizures, their doctor may prescribe an anticonvulsant drug, such as Depakote® (valproate); Dilantin® (phenytoin); Keppra® (levetira- cetam); Klonopin® (clonazepam); Lamictal® (lamotrigine); Neurontin® (gabapentin); Tegretol® (carbamazephine); Topamax® (topiramate); or Zarontin® (ethosuximide) to name a few. Talk with a doctor about the side effects of the drugs, the amount that is prescribed, and the methods of monitoring the specific drug’s effectiveness.

Patients who are taking oral chemotherapy should ask their doctor about possible interactions with anti- seizure medications. Also, some of the drugs may cause severe fatigue. In some cases, switching to another anticonvulsant may result in better seizure control and fewer side effects. Taking the medication on a regular basis is the best way to control seizures.

Where can I go for support?

Patients diagnosed with brain tumors go through a very difficult, life-threatening experience—one that often changes people and the way they look at life. It is normal to experience a range of emotions, including sadness and fear. Symptoms of depression such as decreased pleasure in usual activities, decreased concentration, apathy, withdrawal and mood swings should not go untreated.

Patients or loved ones experiencing symptoms of depression should discuss treatment options with their doctor. Treatment may include anti-depressant medication and counseling with a psychologist, social worker, or clergy experienced in working with patients with life- threatening illness. Other lifestyle habits can also help alleviate depressive symptoms such as eating a healthy, balanced diet, getting adequate sleep, and engaging in regular physical activity.

Many patients and their families also describe positive changes in their lives, including a deeper appreciation of life and greater personal strength. Family and friends, support groups, meeting other survivors, and counseling are some of the ways that brain tumor patients have learned not only to cope, but also to maintain a positive outlook.

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