Glioma

A glioma is a type of primary central nervous system (CNS) tumor that arises from glial cells. The most common site of involvement of gliomas is the brain, but gliomas can also affect the spinal cord or any other part of the CNS, such as the optic nerves.^[1]

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Classification

By type of cell

Gliomas are named according to the specific type of cell they most closely resemble. The main types of gliomas are:

• Ependymomas — ependymal cells
• Astrocytomas — astrocytes
• Oligodendrogliomas — oligodendrocytes
• Mixed gliomas, such as oligoastrocytomas, contain cells from different types of glia.

By grade

Gliomas are further categorized according to their grade, which is determined by pathologic evaluation of the tumor.

• Low-grade gliomas are well-differentiated (not anaplastic); these are benign and portend a better prognosis for the patient.
• High-grade gliomas are undifferentiated or anaplastic; these are malignant and carry a worse prognosis.

Of numerous grading systems in use, the most common is the World Health Organization (WHO) grading system for astrocytoma. The WHO system assigns a grade from 1 to 4, with 1 being the least aggressive and 4 being the most aggressive. Various types of astrocytomas are given corresponding WHO grades.

WHO grading system for astrocytomas

• WHO Grade 1 — e.g., pilocytic astrocytoma
• WHO Grade 2 — e.g., diffuse or low-grade astrocytoma
• WHO Grade 3 — e.g., anaplastic (malignant) astrocytoma
• WHO Grade 4 — glioblastoma multiforme (most common glioma in adults)

The prognosis is the worst for grade 4 gliomas, with an average survival time of 12 months. Overall, few patients survive beyond 3 years. [1] [2]

By location

The gliomas can also be roughly classified according to their location:

• infratentorial : mostly in children (70%)
• supratentorial : mostly in adults (70%)

Symptoms

Symptoms 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.

Pathology

High-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.

Treatment

Standard therapy

Treatment for brain gliomas depends on the location and the grade. 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.

Refractory disease

For recurrent high-grade glioblastoma, recent studies have taken advantage of angiogenic blockers such as bevacizumab in combination with conventional chemotherapy, with encouraging results.^[2]

Experimental therapies

The use of oncolytic viruses or gene therapy using prodrug converting retroviruses and adenoviruses is being studied for the treatment of gliomas.^[3][4]

A small number of low-scale clinical studies have shown possible links between prescription of Carphedon and improvement in a number of encephalopathic conditions, including lesions of cerebral blood pathways and certain types of glioma.^{[citation needed]}

American scientists are also studying the effects of Leiurus quinquestriatus scorpion (Israeli Yellow Scorpion) venom on glioma.^{[citation needed]} They have successfully isolated the peptide chlorotoxin from the venom of the L. quinquestriatus scorpion by means of gel filtration chromatography. The peptide appears to target glioma-specific chloride ion channels within the cancerous glial cells of the brain, where it binds with a high affinity.

In 2006, German physicians reported on a dose-escalation study for the compound AP 12009 (a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human transforming growth factor TGF-beta2) in patients with high-grade gliomas. At the time of the report, the median overall survival had not been obtained and the authors hinted at a potential cure.

As of 2006, additional research started within the past few years is ongoing. Some of the topics included in this research are:

• efficiency of variations in radiotherapy procedures
• drugs to stop the growth of tumors by preventing them to develop blood vessels
• efficiency of combinations of different treatments
• vaccination therapy.

Although there have been individual cases of patients receiving an experimental treatment who still showed no signs of tumor 3 years or even more after the first diagnosis, often a new treatment for GBM will already be considered successful if it significantly increases the percentage of survivors after two years.

A cancer vaccine "Oncophage" is currently showing great promise in clinical trails, 2007.

References