Astrocytomas and Low Grade Gliomas

Astrocytomas are tumors that are believed to arise from precursors of astrocytes – supportive cells of the brain named for their star-like shape. Astrocytomas are the most common of the primary brain tumors. Astrocytomas are histologically graded by their rate of growth (mitotic activity) and nuclear atypia on a scale from Grade I to IV. Grades I and II astrocytomas are the slowest growing tumors, and are also called “low-grade” astrocytomas. Their symptoms develop over an extended period of time. Representing approximately 10 to 15 percent of all gliomas, they generally are found in young patients and have a more favorable prognosis. Unfortunately, low-grade astrocytomas also occur less frequently than their malignant, high-grade counterparts. Low-grade astrocytomas can be further sub-grouped into three tumor types: pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and diffuse astrocytomas (which are by far the most common).

Symptoms

The initial symptoms of brain tumors, such as headache and nausea, usually are the result of increased intracranial pressure caused by the bulk of the tumor or a backup of the cerebrospinal fluid that surrounds the brain and spinal cord. Astrocytic 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 of the mass, low-grade astrocytomas may cause seizures, weakness or numbness in the limbs, impairments in language function, blurred or double vision, gradual changes in mood or personality, and memory loss.

Diagnosis

Imaging studies are an important component of the diagnosis of low-grade astrocytomas . Currently, magnetic resonance imaging (MRI) is the best available imaging modality. Computed tomography (CT) scans also are used. CT and MR scans show the presence of this tumor, which typically does not “enhance” when an intravenous contrast dye is given. In some cases, neurological surgeons may employ an MRI scan with frameless stereotactic guidance for preoperative planning purposes. For this study, a high resolution contrast MRI is performed, sometimes requiring that special markers (called fiducials) be placed on the patient’s scalp. The MRI scan is processed by a computer, and a three dimensional brain model is constructed. This can be used in the operating room to minimize the size of the surgical exposure, maximize tumor removal, and minimize injury to the surrounding brain.

Treatment

Surgery for low-grade gliomas involves obtaining tumor tissue by either biopsy or resection for a careful analysis and pathological diagnosis. Usually surgery is performed with a frameless stereotactic navigation system in which a high-resolution MRI is used to construct a 3-dimensional brain model – much like a GPS system – that allows for minimally invasive volumetric brain 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. These techniques allow the surgeon to safely remove the maximum amount of tumor tissue without causing neurological harm to the patient. With contemporary surgical techniques a significant, near-total or gross total resection can be achieved in an increasing number of patients.

When a tumor is removed, it can be examined under a microscope to provide an accurate diagnosis so the next steps in treatment, which may include radiation therapy or chemotherapy, can be determined. For some Grade I gliomas (e.g. pilocytic astrocytomas) with sharply defined boundries, gross total surgical removal can confer a cure. However, surgery alone will not provide a cure for other Low Grade gliomas and diffuse astrocytomas where the tumor usually has already grown tiny microscopic tentacles that spread into the surrounding brain tissue. Those tentacles cannot always be seen by the neurosurgeon. They also intermingle with brain cells that are performing their normal important functions. As a result, “complete” safe tumor removal may not be possible. The extent of surgery depends on the location of the tumor, the patient’s symptoms and personal preferences.

The choice of treatment after surgical resection usually factors in the exact tumor subtype and grade, the molecular profile of the tumor (which can predict responsiveness to chemotherapy) and the extent of resection. There is no single approach that can be recommended for all patients. More insights may come from further studies looking at whether a tumor’s chemical and molecular makeup helps to predict whether one type of treatment will be more effective than another. For example, 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. Incorporating molecular techniques into patient’s tumor analysis will allow for the promise of personalized medicine by targeted cancer drugs.

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.