brain talktm IRSATM Volume 7, Number 1 International Radiosurgery Support Association Malignant Brain Tumors...3 Facts About Tumors

TM Volume 7, Number 1 brain talk TM ISSN 1086-427X IRSA TM George with his daughters Eleven Years With An Astrocytoma/Oligodendroglioma George...
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TM

Volume 7, Number 1

brain talk

TM

ISSN 1086-427X

IRSA

TM

George with his daughters

Eleven Years With An Astrocytoma/Oligodendroglioma George’s first hint of a tumor were the seizures he began experiencing in 1989. “I was a real estate broker,” he says, “and I’d go swimming at lunch for thirty-five to forty minutes. I’d swim hard. Then I’d get out of the pool, get dressed and go to the car, and have a seizure.” His family doctor suggested the cause might be low blood sugar from exercising. “He suggested I eat a Snickers or drink Gatorade,” George recalls. “That sounded good, so I kind of buried my head in the sand about what was going on,” he says. “About a year later, I took up karate and my instructor saw me having a seizure.” “I went to see a neurologist the next day,” he states. “She sent me to have an MRI the same day. I could tell by the MRI technician’s face that I had a brain tumor.” “The tumor was in the mid-front section of the right-hand side of my brain,” George explains. The tumor had been causing the seizures on the left side of his body. “My neurologist said to ‘look into it further,’” he remembers. “I went and interviewed several different surgeons in the Seattle area. We were looking into neural brain mapping at the University of Washington.” At the time, George was 36 years old. George had a craniotomy at Swedish Medical Center in Seattle, Washington in November of 1990. The pathologist determined that the tumor was a class II or III astrocytoma. “When I had my first craniotomy, I was in the best shape of my life,” he says. “I was swimming and had just taken up karate.” After the craniotomy, George had six weeks of whole brain radiation. “During the radiation treatments, I commuted from the island every day,” he states. George and his wife Debby live on Bainbridge Island, a commuter island due west of Seattle, Washington, with their two daughters. Mindy, 14, and Elizabeth, 16, attend high school on the island. Bainbridge Island is a 35-minute ferry ride from the mainland. After the radiation treatments, “My hair started falling out,” George reports. “It almost looked like a saddle where they were doing the radiation. It never really grew back.” Continued on page 8

International Radiosurgery Support Association

Malignant Brain Tumors................3 Facts About Tumors ......................6,7

Patient Stories .....................1,2,9,10 Research.........................................8

Stereotactic Radiosurgery

Glioblastoma Multiforme - 12 Years Later

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tereotactic radiosurgery is not surgery. The skull is never opened. Radiosurgery involves the use of precisely directed single fractions of radiation to create lesions within the brain or to treat tumors or vascular malformations with minimal damage to surrounding structures or tissues. This works by delivering a relatively high dose of radiation in one session to the target with scalpel-like precision. The dose is designed to injure or kill the cells or their supporting blood vessels, while minimizing its effect on surrounding healthy tissue. The radiation distorts the cells’ DNA, causing them to lose the ability to replicate themselves. The safety and clinical effectiveness of this technique has been established since 1968 in over 170,000 treated individuals. The benefits include: No risks of infection or anesthesia reactions; virtually no pain; reduced costs; and an immediate return to normal activities. Radiosurgery may or may not be appropriate for your condition. It may be used as the primary treatment or recommended in addition to other treatments you may need. Only a treating neurosurgeon can make the evaluation as to whether you can be treated. Some of the most common indications for treatment today are: • Arteriovenous/vascular malformations • Meningiomas • Acoustic neuromas • Pituitary and pineal tumors • Metastatic tumors • Glial and astrocytoma tumors • All other malignant & benign tumors • Trigeminal neuralgia • Parkinson’s tremors/rigidity • Functional disorders Disclaimer All technical information regarding any technology published by IRSA, in this publication or elsewhere, has been provided by the manufacturer of the equipment. The publisher does not warrant any instrument or equipment nor make any representations concerning its fitness for use in any particular instance nor any other warranties whatsoever.

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Charlie (on right) with his friend, Bruce Editor’s note: Treating physicians are slowly changing how they talk to patients diagnosed with glioblastoma multiforme. In the past, patients were usually told they had less than a year to live. Charlie is one example that a person can have a good quality of life years after diagnosis. Charlie and his wife Joanne aggressively sought and utilized all treatment modalities. Charlie is one of a handful of patients that everyone wants to know about each year. His determination to move on and enjoy life is always an inspiration to others.

Everyone knows Charlie around Marmora, New Jersey, USA. He rides his electric scooter with his golden retriever, Sweety as his companion at his side. Charlie helps his wife Joanne by doing errands and some chores around the house. Charlie is now 63-years-old and is a former administrator who is no quitter. Not even the “tumor stroke” could stop him. At the age of 51, in 1990, Charlie started experiencing tremors which turned out to be focal seizures in his right arm. “It would take on a life of its own, flailing,” says his wife, Joanne. Charlie was working for the New Jersey Department of Education and was involved in rating school districts. He drove 150 miles round trip each day. One day he started having tremors or seizures in his right arm during his commute. “I would just get over to the side of the road and stop and wait until it passed,” Charlie recalls. “It was a pain in the neck. It was scary.” “We thought it was a muscular thing,” says Joanne. “His cousin, a nurse, recommended a neurologist.” This doctor thought Charlie might have a benign meningioma, a tumor on the protective coverings of the brain. In 1991, Charlie had open skull surgery called a craniotomy. The doctors found a 3.5-4cm glioblastoma -

fast-growing, highly malignant brain tumor - on the left side of his cerebral cortex. “After surgery he had more than a 100 stitches and radiation therapy treatments were recommended.” Joanne says. “They gave us a negative prognosis with not much time to live. Radiation was a shot in the dark. They were hoping that would stall the (tumor’s) growth.” After seven weeks of radiation treatment, Charlie’s glioblastoma shrank in half. “At first he had a lot of seizures but they stopped within a month,” Joanne says. “Charlie was determined to work this through. My husband is an extremely positive person.” When early retirement program came up that year, Charlie took it. A year after the craniotomy, Charlie started to suffer seizures again and his right arm and leg were weak. By June, he couldn’t use them. MRIs showed the tumor was growing again. The doctors were not hopeful at this point. He was sent home without follow-up physical therapy. “With prayers to God, we were led to the right doctors,” she says. Later in 1992, Charlie and Joanne sought help from the University of Pittsburgh Medical Center. By this time, Charlie was in a wheelchair with his right side paralyzed. Dr. Douglas Kondziolka, a neurosurgeon at Pittsburgh, asked Charlie, “What do you want us to do?” Charlie said he just wanted to “live as normal a life as possible.” Dr. Kondziolka said this was also his goal. The doctors at Pittsburgh found that Charlie’s tumor was again around 4 cm. They recommended experimental chemotherapy treatment - BCNU and Cisplatin delivered intravenously continuously for three days – once a month for four months. The treatments began in January, Continued on page 11

Primary Malignant Brain Tumors Each year, 8.2 of every 100,000 people in the U.S. are diagnosed with primary malignant brain tumors. They represent approximately 2% of all cancers diagnosed in the United States. Currently, 29.5 of every 100,000 people in the U.S. have primary malignant brain tumors (just diagnosed or under treatment). Primary brain tumors form in the brain and rarely ‘seed’ to other parts of the body. Approximately 13,000 Americans die of malignant brain tumors every year, representing about 2% of all U.S. cancer deaths. Approximately 55% of these deaths are men. The single most important factor related to incidence of and survival from malignant brain tumors is age: the prognosis is more favorable in the under40 age group. Malignant tumors are life-threatening, invade surrounding normal brain tissue, and usually grow rapidly. These tumors generally do not have distinct borders and may spread to other areas in the brain or spine. A brain tumor may be malignant if it invades surrounding tissue, if it is in a critical area of the brain, or if it is lifethreatening. The term malignant can also describe a benign tumor that behaves aggressively, or a benign tumor that is lifethreatening because of its location. Primary malignant brain tumors include: glioblastomas, most of the astrocytomas, and some oligodendrogliomas and ependymomas. All metastatic brain tumors are malignant but are considered secondary brain tumors as they have ‘seeded’ from other areas of the body. What Causes a Brain Tumor? Brain tumors are usually caused by a change in genetic structure. This change in genetic structure may be inherited, caused by the environment, or both. Only a low percentage (5%) of primary brain tumors are associated with inherited genes alone. However, a study by Bondy et al. (1994) showed that 80% of patients with glioblastoma multiforme had more than one copy of chromosome seven. Mutated or missing genes result in abnormal cells. If abnormal cells have malignant potential, they will form a tumor when they multiply. High-dose ionizing radiation, used to treat brain tumors, may on rare occasions

be associated with the production of secondary brain tumors. This most often occurs from radiation treatments that are given over time. People exposed to certain chemicals, such as petrochemicals, pesticides and formaldehyde, appear to be at higher risk of developing a malignant brain tumor than those who are not exposed. In laboratory experiments, some viruses caused brain tumors in animals. It is unknown whether viruses can cause brain tumors in humans. Electromagnetic fields have been under study for some time as there appears to be a connection to brain tumors. There are many environmental and genetic factors that can cause brain tumors. However, in most cases, we just don’t know what causes a brain tumor. Tumor Grading Tumors are graded based on their microscopic appearances. The grade indicates the level of malignancy. Tumors are graded on their mitotic index (growth rate), vascularity (blood supply), presence of a necrotic center, invasive potential (border distinctness) and similarity to normal cells. Malignant tumors may contain several grades of cells. The most malignant grade of cell found determines the grade for the entire tumor, even if most of the tumor is a lower grade. In the World Health Organization grading system, grade I tumors are the least malignant. These tumors grow slowly and microscopically appear almost normal; surgery alone may be effective. However, even a grade I tumor may be life-threatening if it is inaccessible for surgery. Grade I tumors are often associated with long-term survival. Grade II tumors grow slightly faster than grade I tumors and have a slightly abnormal microscopic appearance. These tumors may invade surrounding normal tissue, and may recur as a grade II or higher tumor. Grade III tumors are malignant. These tumors contain actively reproducing abnormal cells and invade surrounding normal tissue. Grade III tumors frequently recur, often as grade IV tumors. Grade IV tumors are the most malignant and invade wide areas of surrounding normal tissue. These tumors reproduce rapidly, appear very unusual microscopi

Dr. Wein

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cally and are necrotic (have dead cells) in the center. Grade IV tumors cause new blood vessels to form, to help maintain their rapid growth. Glioblastoma multiforme is the most common grade IV tumor. Common Malignant Primary Brain Tumors Tumors are named for the cell types from which they originate. Glioma is the general name for a tumor that arises from the glial tissue, which supports and nourishes the brain. There are several different kinds of glial cells: astrocytes, oligodendrocytes and ependymal cells. Gliomas are the most commonly diagnosed of both benign and malignant primary brain tumors, accounting for approximately 45-50% of all primary brain tumors. The most common gliomas are: astrocytomas, ependymomas, oligodendrogliomas and tumors with mixtures of two or more of these cell types. Grades I and II astrocytomas account for 25-30% of all gliomas. The most frequently diagnosed types of astrocytoma are pilocytic astrocytoma, grade II astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. Astrocytomas Pilocytic Astrocytoma Pilocytic astrocytomas, which are grade I tumors, are considered benign because they do not invade the surrounding normal brain tissue. These are slow-growing tumors, but can become very large. Pilocytic astrocytomas frequently have cystic portions filled with fluid and a nodule, which is the more solid portion. They are the Continued on page 4 Brain Talk, Volume 7, Number 1

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Malignant Tumors Continued from page 3

most commonly diagnosed brain tumor in children aged 15-19. Most pilocytic astrocytomas are located in the cerebellum. The cerebellum is responsible for coordination, so most symptoms of this type of tumor are related to balance or coordination difficulties. Grade II Astrocytoma These tumors invade surrounding healthy tissue but grow relatively slowly. This group of tumors includes low-grade astrocytomas and fibrillary or protoplasmic astrocytomas. Mixed gliomas, which contain astrocytoma cells and either oligodendroglioma or ependymoma cells, or both, are commonly graded II or III. Astrocytomas are the most commonly diagnosed brain tumor in children aged 1014. Astrocytomas comprise 8% of primary brain tumors. Anaplastic Astrocytoma Anaplastic astrocytomas, which are malignant tumors, comprise 4% of primary brain tumors. This type of grade III tumor grows more rapidly than lower grade tumors and tends to invade nearby healthy tissue. Anaplastic astrocytomas recur more frequently than some lower grade tumors, because their tendency to spread into surrounding tissue makes them difficult to completely remove surgically. An anaplastic astrocytoma can be a reoccurrence of a lower grade, previously treated astrocytoma. Glioblastoma Multiforme Glioblastoma multiforme, a grade IV tumor, is a malignant astrocytoma that contains areas of dead tumor cells. Gliosarcoma and giant cell glioblastoma are variants of glioblastoma multiforme. Approximately 50% of astrocytomas are glioblastomas. Glioblastomas typically contain more than one cell type. While one cell type may die off in response to a particular treatment, the other cell types may continue to multiply. This characteristic makes glioblastomas very difficult to treat. Glioblastomas comprise 23% of primary brain tumors in the U.S., and are the most commonly diagnosed brain tumor in adults aged 45-74. Men are more frequently diagnosed with glioblastoma multiforme than women.

Oligodendrogliomas and Ependymomas Oligodendrogliomas are slow-growing, sharply defined tumors. Oligodendrogliomas comprise 3% of primary brain tumors. Seizures are usually the first symptom of an oligodendroglioma in 50% of patients. Most oligodendrogliomas are mixed gliomas, containing both oligodendrocytes and astrocytes. Oligodendrogliomas may be malignant. Ependymomas are slow-growing tumors. They may be either benign or malignant, based upon their type and location. Types of Treatment Various treatments may be used to treat a malignant brain tumor. The type and number of treatments given is dependent upon many factors, including the size of the tumor, its growth rate and the symptoms the patient is experiencing. Patients should realize that there is more than one way to treat their tumors and should seek medical treatments where many options and a continuum of treatments are available. Surgery Tumors may be surgically removed by the open-skull procedure called craniotomy. When a patient presents with symptoms that are either life-threatening or significantly affect the quality of life, a craniotomy is usually the first treatment offered. Even partial surgical removal may alleviate symptoms and facilitate treatment of the rest of the tumor. A tumor may not be surgically removed if it is in an inaccessible location or too near to critical structures, meaning that the removal of the tumor might further cause great damage to other areas of the brain. Also, surgery may not be performed if the patient is not healthy enough to tolerate the surgery. Surgical biopsies of brain tumors are no longer considered absolutely necessary because of the development of new imaging techniques. With the current scanning

ability with contrast dyes, CT and MRI scans, a brain tumor may be diagnosed as malignant or benign without opening the skull for a biopsy. There has always been controversy over whether the act of obtaining a biopsy may allow the spread of cancerous cells to other brain areas. When surgery is required, a high-powered microscope may be used during the operation. This is called microsurgery. The surgeon uses the microscope to magnify the surgical field. Newer technologies, including intraoperative neuronavigation, allow the surgeon to visualize the extent of tumor resection on a computer screen during the operation. This enables the surgeon to be more aggressive with tumor removal while avoiding damage to surrounding critical structures. Intraoperative CT and MRI scan capabilities are also available in some centers. Ultrasonic Aspiration and Polymer Wafers Instead of using a scalpel to remove a brain tumor, ultrasonic aspiration may be used. Ultrasonic waves fragment the tumor, and the fragments are removed by suction. After a tumor has been surgically removed by any method, BCNU polymer wafer implants may be inserted at the tumor site. These wafers are biodegradable and release chemotherapeutic agents over time. Stereotactic Radiosurgery Stereotactic radiosurgery is a one-session non-invasive treatment directed by a neurosurgeon. The most common type of neurosurgical radiosurgery is performed with the Gamma Knife instrument. During treatment many beams of cobalt60 radiation enter the brain at different sites, precisely targeted to a focal point within the brain corresponding to the tumor location to act like a scalpel. Individually, these beams are too weak to damage tissue, so normal tissue is not damaged. However, where the

Dr. Weiner with his plane “Merlin”

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Malignant Tumors Continued from page 4

radiation beams converge within the tumor - tumor cells are damaged and will lose the ability to reproduce and perform other cellular activity. There is a limit to the size of a tumor that can be treated with this method, which is generally around 4 cm. Radiosurgery provides a precisely targeted high radiation dosage to the tumor area with very little overlap to healthy tissue. Therefore, multisession radiotherapy may be required for malignant brain tumors that have ‘tentacles’ which have invaded the brain. Stereotactic radiosurgery is used on benign, malignant and metastatic (seeded from body cancers) brain tumors. Radiosurgery may be the primary treatment if the patient is not highly symptomatic and does not require open-skull surgery. It is frequently used in combination with conventional fractionated radiation (radiotherapy) as well. Radiosurgery may be a secondary treatment after conventional surgery that reduced the original tumor or surgery that was performed conservatively so that the healthy brain was not injured. In these cases, radiosurgery acts as a ‘boost’ to assist in killing any malignant cells that may be left in the tumor bed. Radiotherapy Radiotherapy may be used to treat a brain tumor. This treatment is usually directed by a radiation oncologist using one of many types of linear accelerator machines. Radiotherapy is not a one-session treatment like radiosurgery, but occurs over time. The dosage of radiation is not as high as with radiosurgery, and the targeting is not as precise as with radiosurgery. Normal cells may be damaged by this treatment, as the targeting of radiotherapy machines is not as precise as the cobalt machines, such as Gamma Knife. Intensity modulated radiation therapy (IMRT) is one form of radiotherapy that patients may hear about. With radiotherapy, the treatment is given over time, to allow the normal cells time to heal from the radiation. Radiotherapy may be used to kill remaining tumor cells after a surgical resection, or for tumors that are very responsive to this treatment. It may also be used for larger tumors that are unacceptable for radiosurgery. In some cases, radiotherapy is used after a patient has had open-skull surgery and radiosurgery. Radiotherapy

may be especially effective for the spreading areas of the tumors that are invading healthy tissue. Multi-session radiotherapy and IMRT, are not usually recommended for young children because their brains are still in a developmental stage and are very susceptible to long-term permanent developmental damage. The normal cells in the radiation path, would have long-term effects which may result in permanent memory, speech, intellectual deficits. Chemotherapy Chemotherapy uses drugs to kill abnormal cells; however, it also affects normal cells. Each year new chemotherapy drugs and combinations of drugs are used in research to find the best drugs to treat malignant brain tumors. The blood-brain barrier to the brain protects the brain from receiving toxic materials and therefore may make efforts with chemotherapy less favorable. Or, more and harsher drugs which are damaging to the body organs may be required in order to pass through the blood-brain barrier. This treatment may be used as a primary therapy in young children or as an adjuvant therapy after surgical removal of a tumor and with radiosurgery. Chemotherapy may not be used if the

tumor does not respond or if the patient is not in good health. Summary Malignant glial neoplasms are the most frequent primary brain tumors and are a leading cause of cancer-related deaths in the general population. Under certain circumstances, highly aggressive multimodal therapy, including extensive surgical resection, fractionated and focused radiation, and intracavitary and/or intra-arterial chemotherapy, can result in prolonged, meaningful survival for selected patients. Intraoperative imaging and navigation techniques allow much more precise and extensive surgical resection, significantly reducing the residual malignant tumor cells that require further treatments in the form of radiation and chemotherapy. Ongoing investigations into molecular control of cell replication and gene transcription hold promise for future control of malignant tumors, creating the possibility of curative surgical tumor excision without tumor regrowth. Dr. Richard L. Weiner, a Board Certified Neurosurgeon is Medical Director of the Gamma Knife Center, Presbyterian Hospital, Dallas, Texas and Clinical Associate Professor of Neurosurgery at the University of Texas Southwestern Medical School, Dallas, TX, USA. He may be reached by phone at +214-750-3646 or by email at: [email protected].

Commentary on Malignant Tumors: Dr. Weiner has presented a very thorough overview of malignant brain tumors, including the various acceptable methods of treatment. He accurately points out in his summary that multimodal therapies available include surgical resection, fractionated or focused radiation and intracavity and/or intra-arterial chemotherapy. The use of one or more of these modalities may well lead to increased quality of life and survival for selected patients. Treatment for malignant brain tumors, whether primary or metastatic, is continually changing. Only a few years ago patients with multiple brain tumors, tumors in what are considered inoperable locations within the brain, or patients with health problems preventing anesthesia had few options. We now have new tools in our armamentarium to treat such tumors. The best outcomes thus far for treating malignant primary brain tumors are obtained when the neurosurgeon resects as much tumor as possible with a minimum of morbidity and secures an accurate histological diagnosis with subsequent fractionated radiation and a possible boost dose of radiation using radiosurgery. Metastatic brain tumors may present different problems in that they may be multiple and located in entirely different locations in the brain, and some may be in areas that are hazardous to operate upon. Radiosurgery delivered by the Leksell Gamma Knife unit or with a modified linear accelerator may significantly improve tumor control and quality of life. The literature supports the fact that radiosurgery alone can result in tumor control rates as good as surgery in selected patients with solitary brain metastases. In our quest to improve outcomes for malignant tumors, both primary and metastatic, the multi-modality approach has been shown to be extremely independent with each having its own significant effect. In selected cases significantly better outcomes may be achieved utilizing radiosurgery.

David L. Cunningham David L. Cunningham, M.D. Associate Professor, Department of Neurosurgery, University of Tennessee Medical Director , Memphis Regional Gamma Knife Center 220 South Claybrook, Memphis, TN 38104 USA Ph: 901-726-6444, E-mail: [email protected]

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Brain Tumors In General:

Malignant Brain Tumors:

◆ The majority occur in the upper part of the brain ◆ Pineal region and ventricle brain tumors occur less frequently ◆ Almost 35,000 people are newly diagnosed annually with brain tumors in the USA ◆ Incident rate of primary malignant brain tumors for USA is 6.6 per 100,000 ◆ The incident rate is highest in white Americans (6.7 per 100,000) ◆ African-Americans and Asians (3.7 per 100,000) have the lowest incident rate ◆ Males have primary malignant tumors at the rate of 7.0 per 100,000 ◆ Females have primary malignant tumors at the rate of 4.8 per 100,000 ◆ People over the age of 65 have more malignant brain tumors

◆ Is life-threatening, invasive, and usually grows rapidly ◆ May be call brain cancer ◆ Rarely spread outside the brain ◆ Have unregulated growth of abnormal cells ◆ Invade local brain structures ◆ Interferes with normal functioning

Pilocytic Astrocytoma: ◆ Grade I tumors ◆ Considered benign ◆ Do not invade surrounding tissue ◆ Slow-growing ◆ Most commonly diagnosed brain tumor in children aged 15-19

Hemangiopericytoma: ◆ Is a rare grade II or III tumor ◆ Found on the dura mater, which is the outer layer of the meninges ◆ Commonly spreads to bone, lungs and liver ◆ Frequently recurs ◆ May invade brain tissue ◆ Is malignant

Gliomas:

Childhood Brain Tumors:

Malignant Brain Tumor Facts

◆ Arise from the connective tissue of the brain ◆ Are the most common of all brain tumors ◆ Astrocytomas, glioblastomas, oligodendrogliomas and ependymomas are gliomas ◆ Account for about 50% of all brain tumors ◆ Choroid plexus and mixed neuronalglial tumors are uncommon gliomas

Oligodendroglioma: ◆ Represents 3% of primary brain tumors ◆ Seizures are first symptom in 50% of patients ◆ Most are mixed gliomas ◆ May be malignant ◆ Often contain mineral deposits

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◆ Almost 3,000 primary brain tumors were diagnosed in 2001 ◆ Second leading cause of cancer deaths in children in the USA ◆ Typically not treated with radiation unless child is 3 or older ◆ Astrocytoma is most commonly diagnosed brain tumor in age 10-14 ◆ Brain stem gliomas represent about 10-20% ◆ Medulloblastomas represent about 15-20% ◆ PNET and medulloblastomas are most commonly diagnosed brain tumors in age 0-9

Glioblastoma Multiforme: ◆ Is a grade IV astrocytoma ◆ Is malignant ◆ Represents approximately 50% of astrocytomas ◆ Usually contains more than one cell type ◆ Represents 23% of primary brain tumors in the U.S. ◆ Most commonly diagnosed brain tumor in adults aged 45-74 ◆ Represents 9% of brain tumors in children ◆ Men more frequently diagnosed with this tumor than women

Common Symptoms of Brain Tumors:

Causes of Brain Tumors:

◆ Symptoms are often vague and may mimic other problems ◆ Symptoms may develop gradually which can delay diagnosis and treatment ◆ Symptoms are most specific when related to the location, type and size of brain tumor ◆ Increased intracranial pressure occurs from the tumor’s displacement of the brain tissue as it grows ◆ Increased intracranial pressure may cause nausea, vomiting, drowsiness, vision problems, limb weakness, and mental changes ◆ Other common symptoms are: headaches, seizures, memory confusion, speech and concentration problems ◆ Focal symptoms may help identify the location of a brain tumor ◆ Focal symptoms may include ringing/buzzing in the ear, hearing loss, balance problems, decreased muscle control among others

◆ We do not know the cause of most brain tumors ◆ Research on many levels is being conducted ◆ It is believed that altered (mutated) or missing genes may enable some tumors to develop ◆ Hereditary factors may play a part in some tumors ◆ Environmental factors like chemicals, viruses, and electro magnetic fields may cause tumors ◆ For more information search the National Institute of Health’s literature site at www.ninds.nih.gov (type ‘Medline’ in the search box, then search on any term)

Chondrosarcoma: ◆ Is composed of cartilage ◆ Is malignant and invasive ◆ Commonly found at the base of the skull ◆ Very rare

Ependymoma: ◆ Represent about 6% of all gliomas and 10% of all childhood brain tumors ◆ Many types of ependymomas ◆ May be benign or malignant ◆ May spread through the cerebrospinal fluid

Anaplastic Astrocytoma: ◆ Is malignant ◆ Represents 4% of primary brain tumors ◆ Grade III ◆ Is invasive ◆ May be a reoccurrence of a lower grade, previously treated astrocytoma

Medulloblastomas: ◆ Represents 15-20% of childhood brain tumors ◆ 30% of all medulloblastomas occur in adults ◆ A fast-growing, invasive tumor that spreads to other areas of the brain ◆ On rare occasions may spread to the body and spine

For More Information:

PNET: (Primitive Neuroectodermal Tumor)

◆ The American Brain Tumor Association 800-886-2282 or visit www.abta.org

◆ Occur primarily in the cerebrum ◆ Usually occur in young children ◆ Contains undeveloped brain cells ◆ May have areas of dead tumor cells and cysts ◆ Highly malignant and tend to be large tumors

◆ The National Brain Tumor Foundation 800-934-2873 or visit www.braintumor.org ◆ The Brain Tumor Society 800-770-8287 or visit www.tbts.org

Combination of Treatments May Be Best for Malignant Tumor

In many instances, the best treatment for a malignant or metastatic tumor may be a combination of many treatment modalities. Research suggests the best outcomes and best quality of life may occur when combinations of surgery, radiation therapy (brain and body), stereotactic radiosurgery (brain only), conformal radiation (brain and body), and chemotherapy are utilized to treat body cancer or brain tumors. Research also suggests that less time between each of these various treatments, depending upon the specific patient’s condition, may provide the best result for a cure or lengthening survival with substantial quality of life. Adjunct treatments such as surgery and radiosurgery in combination may be the best treatment available when an aggressive or recurring benign brain tumor is being treated. Brain Talk, Volume 7, Number 1

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Eleven Years Continued from page 1

Despite the surgery and radiation, “I kept having localized seizures in my left hand,” he says. To control the seizures, George began taking Tegretol, Dilantin and clorazepate. He has been taking these medications since 1990. “I kept having the mild hand seizures, but the medications weren’t controlling it,” he states. An MRI also showed that the tumor was growing back. His neurologist referred him to Northwest Hospital in Seattle. In August of 1998, George underwent Gamma Knife radiosurgery at Northwest Hospital. The surgery was performed by Dr. Peter Balousek. “I had PET scans first at the University of Washington to confirm whether it was brain tissue or a tumor,” George recalls. “I started having a balance problem,” he relates. “The original cyst [tumor bed] was filling up with fluid, probably spinal fluid. It was pressing on the brainstem. So I had a shunt put in, in the summer of 2000.” “The shunt would fill up about every four weeks,” he says. “I could tell because my left side would start dragging.” By the time four weeks had passed, “I was almost dragging my leg up the stairs.” George would go to the hospital every four weeks to have the shunt drained. “After they drained it, I could almost do

Fast Facts: Primary Malignant Brain Tumors ◆ Occur at a rate of 6.6 per 100,000 population ◆ Are the second most common cause of cancer death among those under age 35 ◆ Are known to recur as a higher, more malignant grade ◆ About half of all brain tumors are malignant jumping jacks,” he recalls. “It got to where it was filling up less and less.” George had another Gamma Knife radiosurgery with Dr. Balousek in April of 2000. MRIs showed that an ‘offshoot’ was growing adjacent to the original tumor. “The tumor had come back,” he says, “and the hand seizures had increased to fifteen or sixteen a day. People couldn’t tell that I was having a seizure; my hand would just tremble.” Shortly after the second Gamma Knife surgery, the hand seizures ceased. In July of 2001, Dr. Balousek performed a second craniotomy with neural brain mapping to remove the growth adjacent to the original tumor. “The pathology report showed the tumor was now a class II or III oligodendroglioma with anaplastic

characteristics,” George says. Ninety percent of the tumor had been removed during surgery. After the surgery, George began chemotherapy. “Each round is six weeks long,” he says. He recently began his second round in January 2002. “I put off starting chemo for a while and did some traveling,” he relates. “I went to Hawaii, Mexico and Chile. I also have friends in Alaska that I go see every summer.” “Thank God for my wife because she goes along to all the doctors’ appointments and remembers the details,” he says. “She’s really been a blessing. She’s been a heck of a sport, telling me to get out and travel, and she’ll stay and take care of the kids.” George enjoys playing guitar and traveling. He is also a woodworker. “I play with power tools,” he jokes. “I’ve lived eleven years with this tumor,” he says. “I’ve had over sixty MRIs in the past eleven years!” “When I first started out with this, my surgeons were all twenty years older than me,” he says. “Now they’re all ten years younger than me. I think I’m happier with the steadier hands.” George invites people to contact him. “I’d love to talk to anybody, from anywhere,” he says.

Current Research... Stereotactic Radiosurgery Prolongs Survival GLIOBLASTOMA MULTIFORME... Researchers at the University of Maryland examined the results of treating 64 glioblastoma multiforme patients with either external beam radiotherapy (EBRT) alone or EBRT followed by Gamma Knife radiosurgery. Forty-five and 19 patients had previously undergone craniotomies and stereotactic localization needle biopsies, respectively. Subsequently, 33 patients were treated with EBRT alone, while 31 patients were treated with EBRT and Gamma Knife within four weeks of EBRT. External beam radiotherapy was delivered in a three-dimensional conformal manner. Median survival for the group with EBRT alone was 13 months from the time of diagnosis, while median survival for the group that received EBRT and a Gamma Knife boost was 25 months from the time of diagnosis. — from Neurosurgery 2002;50(1):41-47.

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ANAPLASTIC ASTROCYTOMA AND GLIOBLASTOMA MULTIFORME... During an 8 year period, University of Pittsburgh researchers studied the effect of stereotactic radiosurgery with the Gamma Knife on the survival of patients with anaplastic astrocytoma or glioblastoma multiforme. Tumor diagnosis was obtained either through craniotomy or stereotactic biopsy. Sixty-four glioblastoma multiforme patients and 43 anaplastic astrocytoma patients were included in the study. Two year survival time for glioblastoma multiforme patients was 51%, and for anaplastic astrocytoma patients was 67%. The authors concluded that compared to historical controls, radiosurgery provided an improved survival benefit for glioblastoma multiforme and anaplastic astrocytoma patients. Radiosurgery was and well tolerated with no acute neurological complications after treatment. Further studies with radiosurgery as an adjunct treatment are warranted. — from Neurosurgery 1997;41(4):776-785.

Hemmorhage At Age 65: First Sign Of AVM Editor’s note: this story was kindly written and contributed by Jim. He hopes to go to Moscow in May to coach baseball.

I am a single, adult male living alone in northern New Mexico. I have an ex-wife living in Ohio and two adult children living in Ohio as well. I was 65 years old at the time of my arteriovenous malformation/subarachnoid hemorrhage (AVM/SAH). I lived a somewhat active life. I play baseball and tennis, and I ski. I taught skiing in Taos for five years. I am also a published writer. At the time of my AVM/SAH I was fully retired spending much of my time playing baseball and tennis. I have enjoyed good health throughout my life. As a matter of fact, I had not had an overnight stay in a hospital since I was 19 years old. I had been to St. Petersburg, Russia early in 1997 with a men’s tour group to meet Russian ladies. I enjoyed Russia so much that I desired to return to Russia as a baseball coach. I took a similar tour to Ukraine the next year. Later I had a rendezvous with a Russian lady in Paris. On July 29, 1999, during strenuous activity, I experienced a sudden piercing headache and a strange feeling in the base of my neck. I felt a slight dizziness as well. In retrospect I think I even sensed a pop in my brain. Since I almost never have headaches, I knew something was not exactly right and that this was not a simple headache. I contacted my family physician and he suggested (if I recall correctly) that I come to his office. I went to his office and, after he heard my symptoms, he advised me to go to the local hospital for a CT scan. The CT scan revealed some blood in the right rear hemisphere of my brain. The results were discussed with the neurologist in Santa Fe and it was decided that I should make an appointment with the neurologist to go see him in the near future. I don’t recall if I spent the night at the local hospital. I believe I went home with instructions to avoid high blood pressure activities. Soon thereafter (I don’t recall the exact date) I had another “attack.” My family physician was advised and I was driven to the hospital by a friend. The CT scan revealed more blood and it was decided to rush me to the hospital

Jim

and neurologist in Santa Fe. I was taken by ambulance to Santa Fe where more tests were performed, including an MRA and an MRI. The tests revealed the AVM (a tangle of blood vessels) quite clearly. [Editor’s note: An AVM is formed during fetal development and usually exhibits itself before the age of 20.] I remained for several days in the hospital and was advised that sooner or later I would require some form of treatment. I was sent home with a requirement to schedule the treatment in Phoenix. Within a few days of my confinement at home I had another, somewhat severe “attack.” I was rushed to the local hospital and was then sent by medical helicopter to Santa Fe. After some tests and observation, it was decided by the neurologist to rush me to the neurosurgeons in Phoenix. I was flown by a medical jet aircraft to Phoenix. After a series of tests and observations by the doctors from the Barrows Neurological Institute, in Phoenix, Arizona, I was advised that I would require treatment. They explained the treatment options: 1) an insertion of a glue-like substance into the blood vessels which lead to the AVM (embolization), 2) treatment with the Gamma Knife (stereotactic radiosurgery), or 3) open skull surgery to remove the AVM. With total naive faith I agreed to everything except option three. The first treatment was to insert the “plug” into the blood vessels. This treatment was totally painless and had no side effects. The doctors then explained that the Gamma Knife was also required. By this time my son had come from Ohio to be with me.

The actual Gamma Knife procedure was quite fascinating to be a part of. It too was totally painless and I had no after effects. I recall the process of the doctors drilling holes in my skull and screwing the helmet device into my skull. I recall very little after that. My son took photographs of the whole procedure but, unfortunately, the camera was misplaced. I was advised that the Gamma Knife procedure would take 18 to 24 months to have a full effect of resolving the AVM. [Editor’s Note: Until radiosurgery has resolved the AVM, there would be the same risk of future bleeding.] My total stay in Phoenix was at least a week (if I recall correctly). My son accompanied me back to Taos and remained with me for two days. Although I felt competent to manage my own affairs I had some assistance from a local visiting nurse and some housecleaning assistance. After my treatments I had several incidents of additional bleeding accompanied by headaches. The doctors were not alarmed by this and indicated that it was residual blood in the brain. If the additional bleeding incidents occurred too far into the future, the doctors suggested that additional treatments would be required. Fortunately, the incidents ceased sometime in September of 1999. For a long period of time after September of 1999, I limited my activities to sedentary ones. No longer were baseball, tennis and skiing part of my life. This was not easy to do. I resumed a somewhat normal regimen in the Spring of 2000. I began playing tennis, but not baseball. I resumed skiing in December of 2000, and resumed baseball in the Spring of 2001. As to side effects, there have been and still exist some physical side effects from the hemorrhaging. Fortunately there have been no effects on my intellectual activity. I’ve almost mastered a new language since - Russian. The physical side effects have been on certain athletic skills, and I am still working on trying to reverse the effect. In tennis, I have lost some of my coordination skills. My ball toss is way off. (The bleeding and treatment was on the right side of the brain and I toss the ball with my left hand.) I am most affected by balls which are hit straight at me. I also have lost some of my baseball skills. I was never a really Continued on page 12 Brain Talk, Volume 7, Number 1

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26 Year Old Diagnosed With Malignant Hemangiopericytoma

Shawn

Two years ago, Shawn went to see his family physician about a bump on his head. His doctor thought it might be a cyst, and sent him home. The next year, he went to the eye doctor for a checkup. “He said my optic nerve looked strange,” Shawn recalls, “and he sent me to the emergency room.”

Shawn was diagnosed with a hemangiopericytoma, a rare malignant tumor located on the dura mater, which covers the brain. “The tumor had been growing and pushing on my optic nerve,” he says. “The bump that I had on my head was really the tumor pushing through my skull.” Two days later, in May of 2000, he underwent a craniotomy to remove the tumor. Since the tumor is not in the brain but invades the skull, his craniotomy recovery is easier and damage is less than with surgeries that invade the brain. “A scan three months after surgery showed a small regrowth in the area of the sagittal sinus,” he states. A few months after the surgery, Shawn began multi-session (IMRT) intensity modulated radiation therapy with the Peacock“ system. IMRT allowed the area of spread of the tumor to be treated with some preciseness of radiation to reduce the amount of radiation that would overlap into the healthy tissue. In October of 2000, Shawn had Gamma Knife radiosurgery to the tumor bed to try to stop the tumor regrowth. Radiosurgery is one-session and is the

most precise of all radiation treatments and allows for the least overlap of radiation to healthy tissue. Clinically, it has been found to be very effective. Unfortunately, the tumor kept growing as many malignant tumors do. “I had another craniotomy in August of 2001,” he says. He was scheduled for more multi-session radiation treatments, but “I put them off so I could go to Europe,” he adds. Shawn went to Paris, a trip he won through a sales contest. He is an institutional insurance agent, selling insurance to employers, which they then offer their employees. “I used to work at an ad agency,” he says. He later realized it was not what he wanted to do. While in France, he had dinner at the Palace of Versailles and stayed in castles. “Next I’ll be going to Jamaica,” he says, “and maybe St. Petersburg.” When he returned from Europe, Shawn was ready to begin radiation treatments. However, the doctors found more tumor growth. The next month, at age 27, he had two more craniotomies. He again had more IMRT treatments after the last craniotomy. Continued on page 12

Lucky Accident Reveals Neurocytoma Editor’s note: we first brought Robert’s story to you five years ago. We are pleased to update his story for those of you who have repeatedly asked how Robert is doing.

In July 1996, 13year-old Robert was thrown from his all-terrain-vehicle while riding through a creek bottom. It was probably the luckiest day of his life. Robert did not hit his head but experienced a severe headache, was disoriented and could not speak correctly. He was eventually taken to the University of Kentucky, where an MRI showed a suspicious mass or bruise in his brain. The doctors would have to wait for healing to occur to tell what was really there. After several weeks, Robert began to have seizures and headaches, with more related confusion and speech problems. A biopsy into the three-inch-deep mass confirmed that Robert had a neurocytoma. The tumor was deep within the left frontal lobe and considered inopera-

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Brain Talk, Volume 7, Number 1

ble. And now it was beginning to cause severe problems. Eventually, the tumor would threaten Robert’s life. He was a perfect candidate for the one-session Gamma Knife neurosurgical radiosurgery. IRSA made the treatment easier for Robert by selecting him to represent the 60,000th Gamma Knife treatment worldwide and giving him and his family a small trip to Disney World in June of 1997. Robert was now sold on the idea of treatment! He and his family went for treatment with Dr. Byron Young at the University of Kentucky Gamma Knife Center in February of 1997. Robert’s treatment went like clockwork and he walked to his room afterward. Two days later, he was back in school and “shooting hoops” with a friend. He became a local celebrity with a wonderful article written about him in the local newspaper. Five years later, Robert has just turned 19. The family had been told that

Robert

it might be 10 years before they would know if Robert was “out of the woods.” Last June, Robert graduated from high school. He is now attending college, and is interested in computer drafting. He also enjoys playing the drums. Robert’s last seizure was on his graduation night, but he has not had one since. He is able to drive now, and works part-time. Continued on page 11

Lucky Accident Continued from page 10

His last MRI in August 2001 showed the tumor shrunk and the hole where the tumor was located is now a little smaller. He is scheduled for another MRI in a few weeks.

Glioblastoma Multiforme Continued from page 2

1993. Today, Joanne jokes about how they spent the early 1993 holidays in the Steel City - their anniversary in January, Valentine’s Day in February, St. Patrick’s Day in March and Easter in April. “We’re 10 hours driving time from Pittsburgh , so we fly by plane each time,” Joanne says. “The chemotherapy really tired Charlie and had some side effects so that he would need a couple of days to get back on his feet” before they could fly back to New Jersey. “He usually had one day of upset stomach after chemotherapy, but they gave him a lot of medication to combat that,” Joanne recalls. “By the second week at home, he was feeling weak and tired,” but still kept up with his physical therapy. “By the time he was feeling well again, it was time to go back to Pittsburgh” for the next round of chemo. The experience was “unbelievable,” Charlie says. He used meditation, which he taught himself, to make it through the treatment. “It works,” he says. While he was being treated, Joanne stayed at a nonprofit Family House facility for families and patients that costs less than hotels. The goal of the chemotherapy was to shrink Charlie’s tumor down enough for Gamma Knife surgery. At the end of the third session, Charlie says he knew the treatment had worked. His body felt different and “I had a feeling that it was over.” In April, tests showed the experimental chemotherapy had indeed done its job: Charlie’s tumor had shrunk enough that he could have Gamma Knife surgery. He was treated in May 1993. Since then, MRIs have shown no significant growth in Charlie’s glioblastoma. He has an MRI done on a regular basis near his home in New Jersey and it’s sent immediately to Pittsburgh. “Dr. Kondziolka and his staff have been always kind, caring and extremely sensitive to our needs through all these years,” Joanne

says. “They truly are a class act,” and continue to follow Charlie even now 12 years later. Charlie’s right side is still partially paralyzed, but he can use a walker and his electric scooter to get around. He continues to work in staying active to keep his right side in good shape. He also works on exercises to assist his memory in recalling letters and numbers. “You have to keep working on it and the skills return,” Joanne says. “He reads a lot. But writing is a problem.” Charlie’s speech was also affected. He can formulate ideas in his mind, but can’t always express them, or the words come out backwards. “It can be frustrating because he knows what his mouth wants to say, but he can’t always say it,” Joanne says. Even with the problems both Charlie and Joanne agree that “he has good quality of life.” Charlie maintains an active daily schedule. Charlie’s constant companion, his golden retriever, Heather, had to be ‘put down’ as she was found to have had cancer throughout her body. This was especially hard for the McGuires. They had a new golden retriever named ‘Sweet Dreams’ which they lovingly call ‘Sweety.’ Sweety roams the neighborhood everyday with Charlie. “We have a couple of cats, too, and they’re my passion,” Joanne adds. Prior to 1990, Charlie was very active in his church and the community. He served as an emergency medical technician and was in the National Guard. So tumor or no tumor, “he was absolutely determined to get out,” Joanne says. “Everybody in our town knows him. He goes everywhere with the scooter and the dog.” Charlie adds: “It’s a nice feeling. The neighbors are a big help.” Charlie and Joanne stay active with friends and have two adult children. “It’s a good life,” Charlie says. “I’ve been lucky to have Joanne.” For her part, Joanne says, “He’s a more positive person than I have ever been, so I’ve learned a lot from him. We don’t look at this negatively at all. There are no pity parties here. “Charlie’s best friend, Bruce, comes over every Sunday and they spend a couple of hours together,” she says. “They watch golf and football games.” Charlie is about to have another MRI. He gets them once a year. “It will be 10 years in 2003 since Charlie started treatments at Pittsburgh,” Joanne says. “He’s doing well.”

brain talk Volume 7, Number 1

T

he International Radiosurgery Support Association is an independent organization dedicated to providing information through personal contact and educational materials, encouraging research and promoting patient options about radiosurgery treatment and its availability. ❦ Rebecca L. Emerick Managing Director ❦ T. K. Ledbetter Editor ❦ Tomasz Helenowski Medical-Technical Advisor Chicago, IL USA Contributing Authors and Medical Advisors: ❦ Alan Appley Lafayette, LA USA

❦ Douglas Kondziolka Pittsburgh, PA USA

❦ Ronald Brisman New York, NY USA

❦ Edward R. Laws Jr. Charlottesville, VA USA

❦ Lawrence Chin Baltimore, MD USA

❦ Christer Lindquist London, England UK ❦ L. Dade Lunsford Pittsburgh, PA USA

❦ David Cunningham Memphis, TN USA ❦ Alain C de Lotbinière New Haven, CT USA ❦ Christopher Duma Newport Beach, CA USA ❦ Michael S. Edwards Sacramento, CA USA ❦ Maheep Singh Gaur New Delhi, India ❦ Jordan Grabel West Palm Beach, FL USA ❦ Deane Jacques Los Angeles, CA USA ❦ Jonathan Knisely New Haven, CT USA

❦ Georg Norén Providence, RI USA ❦ Kenneth Ott La Jolla, CA USA ❦ Swaid N. Swaid Birmingham, AL USA ❦ Robert Timmerman Indianapolis, IN USA ❦ Harish Thakrar Chicago, IL USA ❦ Richard Weiner Dallas, TX USA ❦ Aizik L. Wolf Coral Gables, FL USA ❦ Ronald Young Los Angeles, CA USA

BRAIN TALK (ISSN 1086-427X), IRSA’s support publication, is published quarterly by the International Radiosurgery Support Association. Business office located in Harrisburg, PA. Contents copyright 2002 by IRSA. All rights reserved. Call (+717) 671-1701 for information. Disclaimer This publication is not intended as a substitute for professional medical advice and does not address specific treatments or conditions specific to any patient. All health and treatment decisions must be made in consultation with your physician(s), utilizing your specific medical information.

Brain Talk, Volume 7, Number 1

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International Radiosurgery Support Association P.O. Box 60950, Harrisburg, PA 17106-0950 USA Phone: +(717) 671-1701 Fax: +(717) 671-1703

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26 Year Old Continued from page 10

“After the first IMRT treatments, I took the removable face mask that helps you stay somewhat immobile during treatment and put it in the trunk of my car,” he states. “I forgot about it, and it was there about a year. So for the next treatments they were able to use the same mask.” Shawn’s tumor is not in his brain, although it has invaded his skull. “They took out some of the dura,” he says, “and the tumor crossed the midline.” Hemangiopericytomas have a tendency to metastasize, so Shawn and his doctors must be vigilant. Even though he has had four craniotomies, “I’ve only missed a few weeks of work here and there,” he says. “I missed no more than six or eight days of work after each surgery.” Shawn enjoys hiking in the deserts and mountains around Phoenix. “And I exercise between surgeries to get back in shape,” he adds. Shawn is searching for other people with hemangiopericytomas. “It’s really tough to

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find somebody else,” he says. “The one other person that I’ve found with this type of tumor seems to have a less malignant one. He’s had it for twenty or twenty-five years, and is able to treat it like a chronic illness.” Shawn encourages doctors to study treatment options for hemangiopericytomas. “Since it’s so rare, there haven’t been any studies on it,” he says. He’s also searching for a chemotherapy treatment that has been shown to be effective against this type of tumor. He is currently seeking additional therapies.

What is a PET Scan?

◆ Positron Emission Tomography ◆ Measures how cells use sugar ◆ Radioactive tracers concentrate where more sugar is being used ◆ Reveals cancer cells, which use more sugar ◆ For certain indications maybe more precise than CT or MRI

AVM Continued from page 9

great baseball player. Now, I am somewhat of a mediocre player. Recently, two years after my treatment, several tests (including a brain angiogram) were conducted. They revealed that the AVM has not yet fully thrombosed. But approximately two years after the last case of bleeding, the AVM appears to be almost gone. I am scheduled for additional tests in the Spring of 2002. In retrospect, I feel I am fortunate. My family physician recognized my condition well enough to suggest the CT scan in the first place. The neurologist in Santa Fe exhibited his skill in requiring appropriate treatments. And I am also fortunate that the surgeons in Phoenix were as skilled as they were to administer the proper treatments. I am also fortunate that the Gamma Knife treatment was available. If it were not, then I would have to have undergone intrusive brain surgery. Such surgery could certainly have resulted in death or severe brain damage.