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GLIOBLASTOMA MULTIFORME (GBM)

GBMs are the most common and most malignant of the primary CNS neoplasms, representing 15% to 20% of these tumors. Approximately half of all Astrocytomas are GBMs. GBM is the most common supratentorial neoplasm in adults.

GBMs usually occur in patients over 50 and are unusual in patients under 30. Like Anaplastic Astrocytomas, GBMs can occasionally be found at any age; Anaplastic Astrocytomas and GBMs are among the four most common primary Brain tumors in infants and children under 2 years of age.

SYMPTOMS

Various symptoms occur with GBM, including seizure, focal neurological deficits, and stroke like syndromes.

The first symptom of a Brain tumor of any type can be a headache, since these tumors act as masses within the boney skull and thus cause increased pressure in the Brain. The headache associated with a Brain tumor, is frequently worse in the morning and is accompanied by vomiting. Other symptoms of a Brain tumor can include seizures, weakness or numbness of a side or part of the body, or such subtle symptoms such as changes in mood, thinking or general state of well being. Sometimes increased pressure in the Brain can cause blurred, double, or lost vision.

A SEIZURE OCCURRING FOR THE FIRST TIME IN ANYONE OVER THE AGE OF TWENTY MUST BE REGARDED AS THE INDICATION OF A BRAIN TUMOR, UNTIL PROVEN OTHERWISE.

DIAGNOSIS

If a patient has any of the above symptoms, without any obvious explanation, further work-up is warranted. These tumors can be seen best by Magnetic Resonance Imaging (MRI) since the degree of detail is much greater than that provided by CT scans. As with other tumors and most particularly with any of the Gliomas, once a mass is confirmed by any of the imaging techniques, the diagnosis needs to be established by a biopsy of the mass. THE BIOPSY IS USUALLY DONE IN CONJUNCTION WITH AGGRESSIVE RESECTION OF THE TUMOR. The biopsy identifies the particularities of the tumor and differentiates it from other types of masses, such as infection.

Along with primary CNS Lymphoma, GBMs have the worst prognosis of all primary brain tumors. GBMs disseminate early, rapidly, and widely. Central Nervous System spread is common, but distant metastasis is rare.

Figure 2: MRI Scan (Sagittal View-Gadolinium enhanced in the same patient as Figures 1A&B.)

The deeply seated Glioblastoma is infiltrating along fibre tracts from its origin in the thalamic region (Horizontal Arrow) to the Brainstem (Curved Arrow).


TREATMENT

In selecting the treatment of High Grade Malignant Astrocytomas, it should be kept in mind that the following three (3) statistically independent factors affect the length of survival: 1) age at the time of diagnosis, 2) histological features (Grade of the tumor and additional characteristics such as Mitotic Index), and 3) performance status (the level of the patient's neurological capabilities).

Older patients with high grade malignant Brain tumors, who are in poor neurological condition at the time of surgery, do less well.

COMPREHENSIVE THERAPY

The primary initial therapy is to gain control of the increased Intracranial Pressure (ICP). Often times, these patients have significant Brain swelling, in addition to the presence of and as a consequence of the tumor. Pre-treatment with a course of high dose intravenous steroids, may well improve the condition of the patient prior to surgery. In some cases, this may mean a strategic delay of surgical intervention for three (3) to seven (7) days. The wait can be rewarded by a far better initial outcome.


Figures 3 A&B (Left & Center): MRI Scan (Gadolinium Enhanced Axial Views) 68 year old lady with an extensive Right Temporal Lobe Glioblastoma (Curved Arrows).

Figure 3B (Center): MRI Scan (Gadolinium Enhanced Axial View) There is considerable pressure exerted on the Ventricles indicated by the collapse of the Right Lateral Ventricle (Horizontal Arrow) and shift of the midline (Vertical Arrow).

Figure 3C (Right): MRI Scan (Coronal View-Same Patient) showing the extensive edema (indicated by the "white-appearing" material) associated with this tumor which has resulted in considerable increased ICP & "shift" of Brain across the midline. The Arrows indicates how far the midline structures have moved to the Left.


Surgery

Aggressive surgical excision of the tumor is advocated in most patients. The goal is to reduce the maximum amount of the tumor. In some cases this may mean an extensive Frontal or Temporal Lobectomy. When tumor is within the middle or posterior portions of the Temporal lobe, the Parietal or Anterior or Middle Occipital Lobe, an aggressive internal decompression of the tumor is warranted.

It is imperative to understand that there are surgical limitations in the removal of these "infiltrative" tumors because they "spread" along the interconnecting fiber pathways (tracts) of the Brain. As such, these tumors can rarely be entirely removed surgically.

Advanced Technologies Assist Surgery

There are some advanced technologies that currently assist in the extent of resection. The ability of the surgeon to "visualize" tumor is somewhat limited. Magnification of vision, Intraoperative ultrasound imaging, Intraoperative MRI scanning and Intraoperative Fluorescence techniques (See Below) are a few of the adjunctive technologies that may be available to assist maximum resection, while limiting the risk of injuring adjacent functioning Brain.

FLUORESCENCE- Guided Neurosurgery

FLUORESCENCE is one of the most advanced concepts for the surgical management of an infiltrative Brain tumor and the ONLY METHOD that permits the Neurosurgeon to visually identify the tumor that infiltrates Brain tissue. This technique (developed primarily in Europe) involves the ingestion of a medication (5-aminolevulinic acid or "ALA" dissolved in water) that is taken up in certain molecules of the tumor which when subjected to a special violet-blue light beamed through the Neurosurgical Operating Microscope actually( "lights up") glows. Once "seen" under the Neurosurgical Operating Microscope, the surgeon can remove the fluorescent portion by using any of several methods.

Figure 4: Simulated Fluorescence
ALA has been taken up in certain molecules of the tumor which when subjected to a special violet-blue light beamed through the Neurosurgical Operating Microscope actually( "lights up") glows.

Tumor Cell Culture Helps Chemotherapy Decisions

The Neurosurgeons of Neurosurgical Consultants firmly believe that aggressive resection of the tumor, is the first definitive step in the treatment of these tumors. The surgeon may choose to reserve a small part of the tumor for tissue culture in the laboratory followed by sensitivity testing against various chemotherapeutic agents. It can be helpful to know beforehand, if a certain drug has any or limited effectiveness against this particular tumor, in this particular patient. These additional technologies have helped to improve outcomes. We now routinely culture the tumor and subject it to sensitivity testing against various chemotherapy agents prior to initiating Chemotherapy.

Radiation Therapy

Radiation therapy continues to have an important place in the treatment of most of these patients and is the standard adjunct therapy against which other treatments are compared. Refinements have been made that make this treatment less toxic than in previous years. For most patients, this will be the second major treatment option, in a comprehensive therapeutic program.

Chemotherapy

Chemotherapy is the third arm of this comprehensive effort to prolong and maintain a high quality of life. Traditional management has been to use "standard" forms of chemotherapy. Currently there are some unconventional chemotherapeutic alternatives that offer considerable hope for improved quality and length of survival. One of our Neuro-oncologists has utilized these newer medications such as Temodar (temozolamide), Avastin (bevacizumab, an anti-angiogenesis agent) and CPT-11, either alone (or more commonly) in combination or with other drugs, to produce encouraging results. Additional information regarding these treatments is available at the "Virtual Trials".

Direct Chemotherapy

In some tumor cases we choose to place a special chamber called an "Ommaya Reservoir" under the scalp, with an attached catheter residing in the "bed" of the tumor, after resection has been completed. This permits the Neuro-oncologist to instill chemotherapeutic medications directly into the tumor bed. This is a far more effective methodology than placing "chemotherapy wafers in the tumor bed.

Future Therapy

There are several treatment concepts that have considerable interest. Perhaps the most attractive is the potential availability of Gene Therapy to treat Astrocytomas. Another very attractive "surgical" application involves the selective susceptibility of malignant tumor cells to beamed lasers. When this is combined with "Fluorescence-guided" technologies, the surgical management will be dramatically altered.

The following information at WebMD.com may also be useful:

Brain tumors, adult: Treatment - Health Professional Information (NCI PDQ) - General Information



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This page last edited on 2/19

All content ©2016 by Neurosurgical Consultants, P.A.
Author, Martin L. Lazar, MD, FACS
All Rights Reserved. See Usage Notices.