A tumor that arises from glial cells (from the Greek for “glue”), or supportive tissue, of the brain is called a “glioma.” One type of glioma is the astrocytoma. Astrocytomas are named after astrocytes, the star-shaped cells from which they grow. Astrocytomas are histologically graded by their rate of growth (mitotic activity) and nuclear atypia on a scale from Grade I to IV. The terms “malignant glioma” and “high-grade glioma” include grade III and Grade IV gliomas. Glioblastoma multiforme (GBM) is the highest-grade glioma (synonymous with Grade IV glioma) tumor and is the most malignant form of astrocytoma. GBMs are the most common adult primary brain tumors, and make up approximately half of all astrocytomas. They can occur at any age, but are more common in older patients.
Symptoms, such as headache and nausea, usually are the result of increased intracranial pressure caused by the mass of the tumor in the brain or from a backup of the cerebrospinal fluid that surrounds the brain and spinal cord. As a brain tumor grows, it may interfere with the normal functions of the brain. The glial cells are widely distributed throughout the central nervous system, so these tumors can occur in a wide variety of locations, and therefore can cause a wide variety of other symptoms. Depending on the location, gliomas may cause seizures, weakness or numbness in the arms or legs, impairments in language function, blurred vision, changes in personality, cognitive impairments and memory loss. Some GBMs may reach a fairly large size before they begin to cause noticeable symptoms.
These tumors are diagnosed with a neurological examination followed by imaging studies of the brain, usually a computed tomography (CT) or magnetic resonance imaging (MRI) scan. The scan is usually performed with a contrast dye that makes the border and details of the tumor more visible in relation to the surrounding normal brain. The scan provides detail information regarding the exact size, location and probable type of tumor. However, only examination of a patient’s tumor tissue under a microscope can confirm an exact diagnosis. This tissue is usually obtained with either a biopsy or removal of the tumor. In a biopsy, GBM can be characterized by the presence of necrosis, or cell death, which is not present in anaplastic astrocytomas. In some cases, neurosurgeons may employ a stereotactic MRI scan. In this study, a high-resolution contrast MRI is performed and a three-dimensional brain model is constructed using a computer system that is used to perform minimally invasive surgery and allow for volumetric three-dimensional removal of the tumor, which maximizes the degree of tumor removal.
In general, the initial treatment of a glioblastoma is surgical resection of the tumor. With modern techniques, surgery for a craniotomy (making an opening in the skull) is generally safe and allows the team at the Brain Tumor Center to obtain tumor tissue for accurate microscopic diagnosis and treatment planning. With stereotactic volumetric techniques a tumor surgeon can often achieve a gross or near total removal of the tumor when evaluated with an MRI scan after surgery. Removing the tumor tends to reduce the symptoms caused by the presence of the tumor. In some patients with medical conditions that don’t allow for surgery or in patients with concerns about the location of the tumor, a biopsy may be done in place of the surgery.
In some cases, depending on the location of the tumor, the neurosurgeon may employ advanced techniques that enable safe removal of a tumor even in eloquent parts of the brain. Some of these techniques include functional brain mapping to identify the location of movement, sensation and language centers in the brain. This is performed with intraoperative electrical stimulation of the brain, functional MRI scans and occasionally by performing the surgery awake in order to monitor and evaluate these functions during the operation. With stereotactic image-guided techniques the surgeon uses an MRI based 3D model of the patients brain – much like a GPS system – to safely remove as much of the tumor as possible. High-powered microscopes are also used to help the neurosurgeon better see the tumor and ultrasonic aspirators are sometimes used to help remove the tumor.
After surgery, each patient is reviewed at our Multi-Disciplinary Tumor Board with an expert team of neuro-oncologists, medical oncologists, neuro-pathologists, neuro-radiologists and neurosurgeons. Together the tumor board recommends the best treatment options for each patient, incorporating ongoing national clinical trials and the latest treatment protocols. Usually, because the tentacle-like cells of an astrocytoma grow into the surrounding tissue, these tumors require additional treatment around the margins with image guided conformal radiation and/or systemic chemotherapy or targeted biological therapy after surgery. Stereotactic radiosurgery also may be used in some cases of tumor recurrence or to target focal areas of recurrence following chemotherapy. Stereotactic radiosurgery (SRS) and Fractionated stereotactic radiosurgery (FSRS) are special forms of precisely focused, high-dose radiation for delivery to a small, localized tumor as a single dose treatment or fractionated treatment over four to five days.
New therapies, such as immunotherapy, vaccine therapy, gene therapy, and new biologically targeted chemotherapies are being examined. Clinical trials are open for both patients with newly-diagnosed and those with recurrent tumors. These trials test the safety and effectiveness of treatments that have shown promise in earlier phase trials or in laboratory studies. For patients, they provide access to therapies that would otherwise be unavailable. All clinical trials are overseen by government and hospital boards and subject to rigorous regulation and oversight.
Molecular markers have been increasingly used to complement the microscopic diagnosis of gliomas. The promoter methylation of the O6-methyguanine methyltransferase (MGMT) gene and the presence of IDH1 (Isocitrate dehydrogenase) and some IDH2 gene mutations can predict a person’s response to certain chemotherapeutic agents. Gene expression profiling is beginning to be used for evaluating the efficacy of new-targeted molecular drugs. Incorporating molecular techniques into patient’s tumor analysis will allow for the promise of personalized medicine by targeted cancer drugs.