proximal myopathy, diabetes, fungal infections or deep vein thrombosis. Few patients in the older age 
group are able to work after the diagnosis. Most of the patients are incapable of self-care for several 
months before death. The survival depends on the histologic type of the tumor, as well as the location in 
the brain and the functional ability of the patient (measured as the Karnofsky performance status). The 
median survival varies from 58 months for those with anaplastic astrocytoma who are less than 50 
years old with normal mental status, to 18 months for those with glioblastoma less than 50 years old 
and normal Karnofsky status, to 9 months for those with glioblastoma older than 50 years and fairly 
good Karnofsky status. Unfortunately, the majority of patients fall into the last group, so that the 
median survival for all adults with malignant gliomas is 9-12 months [6, 7]. 
As can be surmised from the survival data, treatment for this disease is largely ineffective. Surgery 
and radiation therapy are the primary modalities of treatment, but certain characteristics of the glioma 
render them quite resistant to cure. Surgical resection is a goal in treatment of any localized 
malignancy. Indeed, these tumors are often small compared to cancers elsewhere in the body (less than 
5 cm in diameter at diagnosis), but they cannot be completely removed for several reasons: they lack a 
defined capsule or edge, they infiltrate into normal-appearing brain, and they may be located within or 
adjacent to critical brain regions which cannot be removed without permanently disabling the patient. 
Therefore, partial resection is performed in most cases. In some patients only a biopsy can be done 
safely due to the site of the tumor (Broca's area or the thalamus). Surgery is safer since the wide- 
spread use of corticosteroids, Mannitol, and intra-cranial pressure monitoring; and laser technique and 
ultrasound localization improve the outcome. It is generally believed that partial resection is 
beneficial, in that it creates some space into which the residual tumor can grow before causing pressure 
symptoms. Patients who are able to undergo resection appear to live longer than those whose tumors are 
only biopsied. Second and third resections are occasionally performed for recurrent tumors in patients 
with good performance status. 
Radiation therapy is applied to all patients with malignant glioma, except when the neurologic condition 
is too poor to permit it. The tumors do show response to radiation in many cases, but high doses are 
necessary to achieve control. The normal brain around the tumor can generally tolerate no more than 
60 cGy which is a dose below the curative level for glioma. Therefore, a number of techniques have been 
devised to maximize the tumor dose. Hyperfractionation allows the therapist to deliver higher tumor 
doses by taking advantage of the ability of normal brain tissue to repair sub-lethal radiation damage. 
However, there is little evidence that hyperfractionated radiation therapy results in longer survival, 
despite many trials [7]. Radiation-sensitizing drugs such as Misonidazole and BUdR have been used, 
with little improvement [7]. Interstitial radiation with or without hyperthermia permits the delivery 
of very high doses directly into the tumor and spares much of the normal brain. This technique does 
seem to result in better survival, and even in the eradication of gliomas in some cases. However, it 
results in radiation necrosis of brain in about half the patients, necessitating another operation [8]. 
This technique is applicable to only about 1/3 of patients, since the tumor must be in an anatomically 
accessible location. 
Other approaches to glioma treatment have included chemotherapy, either as an adjuvant to radiation 
[9], or at the time of relapse [10], and immunotherapy, with interferons [11], intra-tumor LAK cell 
instillation [12], radio-labeled monoclonal antibodies or other techniques [13]. None of these methods 
is curative. Adjuvant chemotherapy is helpful in a minority of patients, but probably does prolong 
median survival at least for anaplastic astrocytoma. For the bulk of patients (mostly glioblastoma) 
adjuvant chemotherapy increases median survival only from 9.4 months to 12 months [14]. 
At the time of relapse or recurrence of the tumor, the patient's survival is rarely more than six 
months. If the patient's performance status and the site of the tumor permit it, a second resection is 
usually performed. Chemotherapy given at the time of relapse controls the tumor or provides a 
remission in only about 30 percent of patients. The poor results from chemotherapy may be partly due 
to the inability of most chemotherapy drugs to cross the intact blood-brain barrier at the edges of the 
tumor [15]. Areas of necrosis and areas with poor blood supply within the tumor are less accessible to 
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