Irsa

3002 N. 2nd Street
Harrisburg, PA. 17110 USA
www.IRSA.org

Centers of ExcellenceGLIOBLASTOMAS

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 under-40 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 life-threatening. The term malignant can also describe a benign tumor that behaves aggressively, or a benign tumor that is life-threatening 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 microscopically 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 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 10-14. 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 spreads 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 KnifeÒ 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 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, multi-session 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 accelerators 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 intraarterial 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.

 

© Copyright IRSA® 1995-2014
Terms of Service     |     Medical Advisors     |     Resources     |     About Us     |    Homepage
This information may be copied for personal usage only. Reprints of any portions hereof must obtain prior approval.