Gliomas are a class of tumor that develop from glial (neuroepithelial or support) cells, which compose the supportive tissue of the brain. Cells called astrocytes, ependymal and oligodendroglial are all examples of glial cells. Gliomas comprise nearly one-half of primary brain tumors and one-fifth of all primary spinal cord tumors. Low-grade gliomas are slow growing, and are assigned either a I or II grade. The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread . Grade I tumors resemble normal cells, and tend to grow and multiply slowly. Grade 1 tumors are generally considered the least aggressive in behavior. Conversely, the cells of Grade III or Grade IV tumors do not look like normal cells of the same type
High grade (malignant) gliomas grow much more quickly, and are assigned either a III (anaplastic) or IV (glioblastoma multiforme) grade. Combined, grade III and IV gliomas represent about 40 percent of all primary brain tumors in patients aged 40-49 years, and 60 percent in patients older than 60 years. In most clinical series, grade III tumors comprise approximately 10 percent and grade IV 90 percent of the total number of high grade, malignant primary brain tumors.
Malignant gliomas are one of the most devastating tumors that can affect any given individual. Nevertheless, this past decade, major advances in the fields of molecular biology and cellular biology, as well as genomics, have begun to improve our current understanding of malignant gliomas. Grade IV gliomas, often referred to as glioblastoma multiforme or GBM, possess multiple genetic and chromosomal abnormalities that cause these tumors to grow rapidly. These tumors are unique in their ability to multiply uncontrollably, and aggressively invade, infiltrate and destroy neighboring areas of the brain. However, it is very rare for such tumors to metastasize (spread) outside the central nervous system. As a GBM progresses, portions of the tumor often outgrow the immediate blood supply and die. In contrast, outer regions of the tumor readily supply the growth of new blood vessels (angiogenesis), enabling continued rapid growth of the GBM.
Signs and symptoms of a glioma
The presenting symptom(s) of a glioma depend on the location of the tumor within the brain and its rate of growth. Common symptoms include headaches, seizures, difficulty speaking, weakness/paralysis in one part of the body or face, difficulty with vision, impairment of sensation, impairment of balance, nausea/vomiting, behavioral changes, and impairment of memory or thinking. The clinical course of an untreated malignant glioma is characterized by relentless invasive growth and, even with treatment, near universal recurrence.
How a glioma is diagnosed
The majority of patients harboring a malignant glioma have had one or more of the above mentioned symptoms for a period of several weeks to months. Occasionally, a patient may present with no prior neurological symptoms. In this uncommon scenario, the glioma is discovered "incidentally" on a head CT scan performed on a patient for other reasons, such as an auto accident or a fall with associated head trauma.
In evaluating most brain tumors, MRI of the brain is usually preferred over a CT scan. MRI is better at establishing a probable diagnosis and portraying the suspected brain tumor in three planes, thereby allowing more exact localization of the tumor in relation to critical areas of the brain. Multi-voxel magnetic resonance spectroscopy (MRS) is another way to evaluate gliomas. MRS is a new form of brain scan that uses state-of-art software to analyze radio waves to give a "chemical fingerprint" of a brain lesion non-invasively. Furthermore, positron emission tomography (PET) scanning can provide further information about the chemical functioning of a metabolic potential of a brain tumor. Although these non-invasive diagnostic tests are helpful, the most accurate way to diagnosis a glioma is to examine tissue samples obtained from a biopsy of the tumor. Once a definitive diagnosis has been established, a customized treatment plan is developed for the individual patient, based on his or her unique circumstances.
Treatment options for malignant glioma
Traditional treatment options for malignant gliomas include: surgery, radiation therapy, and chemotherapy.
Surgery is the primary treatment for malignant gliomas. A window is cut into the skull to access the tumor .The goal of surgery is to remove as much of the visible tumor as possible without damaging normal neurological functions. An array of new technologies, such as operating microscopes, microdissection techniques, computerized image-guidance, ultrasound performed during surgery, brain mapping, and most recently, real-time MR imaging, makes removal of gliomas safer than ever. Patients who are able to have 97 percent of the tumor removed appear to have a definite increase in survival, especially if the tumor is located in the frontal lobe of the brain.
Although surgery does not always cure the brain tumor, it can immediately alleviate symptoms caused by the tumor and improve the effectiveness of other therapies; if not removed, some parts of the tumor tend to be particularly resistant to radiation and chemotherapy. Removal of the glioma provides pathologists with the important tissues samples that can better help analyze the tumor.
Radiation therapy and chemotherapy
Radiation therapy and chemotherapy are widely used as secondary treatments following surgery. Both therapies may help suppress the growth of the tumor. Among patients who are not surgical candidates, either radiation or chemotherapy can be used as an initial treatment, but typically only after a biopsy has established the diagnosis of malignant glioma.
Patients who are not candidates for surgery generally include those who:
- are medically unstable
- have multiple active cancers simultaneously
- have tumors spread to both brain hemispheres
- have a glioma in an inoperable location (e.g., brain stem)
- are opposed to surgery
Complications of Radiation Therapy
Patients who undergo radiation therapy may experience some common short-term side effects (which occur in days to weeks). They include fatigue, loss of appetite and nausea. Skin rashes and hair loss often also occur over substantial regions of scalp. Delayed side effects (occurring within months to years) can include varying degrees of memory loss and impairment of reasoning or thinking. More rarely, patients can experience impairment of pituitary function or radiation necrosis (a collection of dead tumor cells and scar tissue). Radiation necrosis can produce symptoms that are often very similar to the initial tumor presentation and include severe headache, motor weakness, visual problems or seizures.
The role of the CyberKnife® (stereotactic radiosurgery) in the treatment of gliomas
Inevitably, high-grade glial tumors will recur (progress) despite aggressive surgical removal and even the best of radiation therapy. To delay tumor recurrence, a large, single, intense dose of radiation (radiosurgery) is sometimes administered. Such radiosurgery is administered to a sharply defined region of the tumor bed after surgery and standard radiation. Unlike conventional radiation therapy, which seeks to suppress the growth of the glioma, the goal of radiosurgery is to create a zone of tumor destruction. In addition, radiosurgery can be used to vaporize glial tumors in patients who are otherwise not surgical candidates, patients who cannot tolerate daily radiation, and patients who are opposed to conventional surgical resection. Whether used immediately following surgery, or at the time of glial tumor recurrence, clinical studies suggest that radiosurgery prolongs patient survival.
Although there are several types of devices used to administer radiosurgery, the principle of delivering a high dose of radiation to a precisely localized target is the same. Some technologies, like the Gamma Knife, use radioactive cobalt as a source of ionizing radiation. A linear accelerator produces the radiation in other devices. Regardless of the source of radiation, nearly all methods of radiosurgery use stereotactic frames that are anchored to the patient's skull with invasive aluminum or titanium screws. The frame serves to accurately localize the tumor in space and immobilize the patient's head. The CyberKnife® is the only radiosurgery device that does not require such a frame for precise targeting. As a result, this instrument uniquely enables doctors treating gliomas to divide a large radiosurgical dose into more than one stage or fraction staged radiosurgery. Staged CyberKnife® radiosurgery is of particular benefit to patients who have previously received large doses of conventional radiation therapy and patients with gliomas located near critical areas of the brain.
Advantages of CyberKnife® radiosurgery for gliomas
In addition to offering the benefits of staged treatment, CyberKnife® radiosurgery also eliminates the pain and discomfort associated with attachment of the head frame used with other radiosurgery devices. With the CyberKnife®, there are no incisions or puncture sites from screw placement, no potential for bleeding or infection, no pain, and no post-procedure recovery time. Furthermore, the unique robotic targeting system of the CyberKnife® makes it possible to better conform a dose of radiation to the often irregular shape of malignant gliomas.
What to expect following CyberKnife® radiosurgery
Following CyberKnife® radiosurgery treatment, patients return home. Infrequently, some patients may experience passing dizziness, lightheadedness or mild headaches. Hair loss after any radiosurgery is possible, but quite unusual, and when it occurs, is usually limited to small portions of scalp. Longer-term use of radiosurgery, including the CyberKnife®, is also associated with a small but definite risk of radiation necrosis. When such a problem arises, symptoms can usually be managed with steroid medications and anticoagulation medications for selected patients.
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