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Orbital Tumors: Optic Nerve Glioma Page... eyeplastics.co.uk | Optic glioma quincymedgroup.com | CANCER - Childhood Visual Pathway Glioma medic8.com | Brain Tumor Center: Glioma brain-tumor.org |
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.[1]
[edit] ClassificationGliomas are classified by cell type, by grade, and by location. [edit] By type of cellGliomas are named according to the specific type of cell they most closely resemble. The main types of gliomas are:
[edit] By gradeGliomas are further categorized according to their grade, which is determined by pathologic evaluation of the tumor. 
Of numerous grading systems in use, the most common is the World Health Organization (WHO) grading system for astrocytoma. [edit] By locationGliomas can be classified according to whether they are above or below a membrane in the brain called the tentorium. The tentorium separates the cerebrum, above, from the cerebellum, below.
[edit] SymptomsSymptoms of gliomas depend on which part of the central nervous system is affected. A brain glioma can cause headaches, nausea and vomiting, seizures, and cranial nerve disorders as a result of increased intracranial pressure. A glioma of the optic nerve can cause visual loss. Spinal cord gliomas can cause pain, weakness, or numbness in the extremities. Gliomas do not metastasize by the bloodstream, but they can spread via the cerebrospinal fluid and cause "drop metastases" to the spinal cord. [edit] PathologyHigh-grade gliomas are highly-vascular tumors and have a tendency to infiltrate. They have extensive areas of necrosis and hypoxia. Often tumor growth causes a breakdown of the blood-brain barrier in the vicinity of the tumor. As a rule, high-grade gliomas almost always grow back even after complete surgical excision. On the other hand, low-grade gliomas grow slowly, often over many years, and can be followed without treatment unless they grow and cause symptoms. Several acquired (not inherited) genetic mutations have been found in gliomas. TP53 is an early mutation. TP53 is the "guardian of the genome," which, during DNA and cell duplication, makes sure that the DNA is copied correctly and destroys the cell (apoptosis) if the DNA is mutated and can't be fixed. When TP53 itself is mutated, other mutations can survive. PTEN, another protein that also helps destroy cells with dangerous mutations, is itself lost or mutated. EGFR, a growth factor that normally stimulates cells to divide, is amplified and stimulates cells to divide too much. Together, these mutations lead to cells dividing uncontrollably, a hallmark of cancer. Recently, mutations in IDH1 and IDH2 were found to be part of the mechanism and associated with a more favorable prognosis.[3] The IDH1 and IDH2 genes are significant because they are involved in the citrate cycle in mitochondria. Mitochondria are involved in apoptosis. Furthermore, the altered glycolysis metabolism in some cancer cells leads to low oxygen (hypoxia). The normal response to hypoxia is to stimulate the growth of new blood vessels (angiogenesis). So these two genes may contribute to both the lack of apoptosis and vascularization of gliomas. [edit] PrognosisGliomas cannot be cured. The prognosis for patients with high-grade gliomas is generally poor, and is especially so for older patients. Of 10,000 Americans diagnosed each year with malignant gliomas, about half are alive 1 year after diagnosis, and 25% after two years. Those with anaplastic astrocytoma survive about three years. Glioblastoma multiforme has a worse prognosis with less than 12 month survival after diagnosis.[4] [edit] Treatment[edit] Standard therapyTreatment for brain gliomas depends on the location, the cell type and the grade of malignancy. Often, treatment is a combined approach, using surgery, radiation therapy, and chemotherapy. The radiation therapy is in the form of external beam radiation or the stereotactic approach using radiosurgery. Spinal cord tumors can be treated by surgery and radiation. Temozolomide is a chemotherapeutic drug that is able to cross the blood-brain barrier effectively and is being used in therapy. [edit] Refractory diseaseFor recurrent high-grade glioblastoma, recent studies have taken advantage of angiogenic blockers such as bevacizumab in combination with conventional chemotherapy, with encouraging results.[5] [edit] Experimental therapiesThe use of oncolytic viruses or gene therapy using prodrug converting retroviruses and adenoviruses is being studied for the treatment of gliomas.[6][7] The European Orphan Status Vaccine and Russian approved vaccine/drug Oncophage, or Vitespen is currently used at the Brain Tumor Research Center at the University of California, San Francisco, which has begun enrolling patients into a Phase 2 clinical trials in combination with the standard of care - radiation therapy plus Temodar (temozolomide) - for newly diagnosed glioma patients. The overall goals of the investigator-sponsored study are to evaluate median overall survival, progression-free survival and immunologic response to vaccine treatment.[8] The FDA has now set a provision allowing patients to receive such care using experimental drugs such as Oncophage to those in need with no other resource for care in the United States. “To date, improvements in overall survival for newly diagnosed glioma patients have been negligible,” said Andrew T. Parsa, MD, PhD, associate professor in the department of neurological surgery at the University of California, San Francisco, and principal investigator of the trial. “The rationale for moving Oncophage into this patient population and combining it with radiation and Temodar was underscored by the encouraging results from the ongoing Phase 2 study in recurrent glioma, a more challenging patient population where the results showed overall survival increasing to approximately 10.5 months.” The experimental cancer medicine "Ukrain" has been used for solid cancers. There are case reports of efficacy on gliomas.[9] Also under investigation is swainsonine.[10] Most glioblastomas are infected with cytomegalovirus, and a clinical trial to immunize glioblastoma patients against cytomegalovirus resulted in slower growth of the tumors.[11] 5-aminolevulinic acid, a drug that makes certain cells, including gliomas, fluorescent, has been used to make surgical removal of gliomas more effective by making it easier to identify and remove them during surgery.[12] [edit] Relative effectiveness of treatmentsA 2007 meta-analysis compared surgical resection and biopsy as the initial surgical management option. Results show that there is insufficient evidence to make a reliable decision.[13] For high-grade gliomas, a 2003 meta-analysis compared radiotherapy with radiotherapy and chemotherapy. It showed a small but clear improvement from using chemotherapy with radiotherapy.[14] For Glioblastoma Multiforme, a 2008 meta-analysis showed that Temozolomide is an effective treatment for "prolonging survival and delaying progression as part of primary therapy without impacting on QoL and with a low incidence of early adverse events."[15] [edit] CausesThe exact causes of gliomas are not known. Hereditary genetic disorders such as neurofibromatoses (type 1 and type 2) and tuberous sclerosis complex are known to predispose to their development[16]. Study suggests exercise during adolescence may cut risk of gliomas in adulthood. HealthDay [17] (10/6, Thomas) reported, "Exercising during adolescence may help guard against" gliomas "in adulthood," according to a study published Nov. 1 in the journal Cancer Research. Researchers "examined data on nearly 500,000 men and women aged 50 to 71" who responded to "questionnaires on height and weight at various points during their lives." They found that participants "who'd reported doing substantial amounts of light, moderate, and vigorous exercise between the ages 15 and 18 were 36 percent less likely to develop glioma than those who were sedentary." The study also showed that "those who were obese during their teen years had a three to four times greater risk of developing glioma than those of a normal weight." Notably, "tall people were also at increased risk of glioma," with "each 10 centimeter...increase" linked to "a nearly 20 percent increase in risk of developing glioma." [edit] Notable casesThe following people are known to have been diagnosed with a glioma: Lee Atwater, Arleen Auger, Severiano Ballesteros, Fred Conlon, Ted Kennedy, Daniel W. Hardy, Dick Howser, Emlyn Hughes, George Gershwin, Gladys Marín, Tug McGraw, Robert Novak, Johnny Oates, Wolfram von Richthofen, Chuck Schuldiner, Kim Walker, Charles Whitman, Allen Shellenberger, Bobby Murcer. In the movie Dark Victory (1939), the character Judith Traherne (played by Bette Davis) is diagnosed with glioma. (at 27:52 in the film) In the movie No Way Out (1950), the character Johnnie Biddle dies of a glioma. In the television series Buffy the Vampire Slayer, the character Joyce Summers (Buffy's Mom) played by Kristine Sutherland is diagnosed in Season 5 with low grade glioma and later dies from complications after surgery once it was removed. [edit] References
[edit] External links
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