I. Introduction 
A. Clinical Background: 
1. Primary Brain Tumors. 
Brain tumors are a major cause of morbidity and mortality in the population. 
New brain tumors develop in approximately 35,000 adujt Americans each year. They 
comprise the third leading cause of death from cancer in persons 15 to 34 years of age 
(1). Recent evidence indicates that the prevalence of primary brain tumors is 
increasing, especially in the elderly (2) . 
The astroglial brain tumors, including the highly malignant glioblastoma 
multiforme (GBM), are the most common primary brain tumors. Despite aggressive 
therapy which includes surgical removal of the tumor and post-operative high dose 
radiation, the prognosis of patients with GBM is very grim with a median survival of 9 to 
1 0 months (3). Although controversial, it appears that neither the quality nor time of 
survival is significantly improved when chemotherapy is added to surgery and radiation 
(4). When glioblastoma multiforme recurs, there is 100% mortality within weeks to a 
few months. In one study, a mean survival of only 36 weeks was found in patients with 
recurrent GBM who underwent a second operation. Unfortunately, a reasonable quality 
of life in those patients was limited to 10 weeks following the diagnosis of recurrent 
GBM (5). 
2. Cerebral Metastases. 
Cerebral metastases are a frequent complication of systemic cancer 
occurring in 20 to 30 percent of patients with cancer (6), (there are 1.1 million new 
cases of cancer per year in the U.S.). In 50% of patients, the metastatic disease is 
localized to the central nervous system (7). A subset of patients may even be cured of 
their primary cancers only to succumb to the isolated metastatic disease in the brain. 
Surgery, combined with radiation therapy, is the treatment of choice for a single focus of 
brain metastasis that is surgically accessible. Median survival using the bi modality 
therapy (surgery and radiotherapy) reaches 40 weeks. In most patients with metastatic 
disease to the brain, multiplicity of the lesions, or their inaccessibility, prohibits surgical 
intervention and limits therapy to radiation alone with a median survival of about 15 
weeks (8). 
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