Brain metastases are a common complication of cancer and alter patient management more than metastases at any other site of distant progression. Supportive therapies include steroids and antiseizure medications. Definitive treatments include radiation therapy, surgery, and chemotherapy. The optimal choice of treatment and overall prognosis largely depend on patient characteristics and the extent and distribution of disease. Delaying or decreasing neurologic cause of death and disability are important therapeutic goals for this population. While better definitive strategies are investigated, physicians must remember to optimize the use of supportive therapies to ameliorate symptoms and maintain quality of life.

Cancer patients are at increased risk for stroke from direct and indirect effects of their malignancy. Some tumors are at high risk for cerebrovascular complications. Certain stroke mechanisms are specific to cancer, such as compression and occlusion of cerebral vessels by tumor, coagulopathy predisposing to hemorrhage and thrombosis, and treatment-related atherosclerosis. Special consideration for these mechanisms needs to be made when evaluating cancer patients, and treatment aimed at secondary prevention needs to incorporate overall prognosis and goals of care.

Patients with large tumors emanating from the posterior fossa aspect of the temporal bone should be evaluated on the basis of their site of origin. Patients with tumors emanating from the anterior or ventral portion of the temporal bone have greater symptoms and greater operative complications than those emanating from the posterior petrous face, between the porus acousticus and sigmoid sinus.

1507 Background: The majority of GBMs overexpress EGFR and have PTEN loss leading to activation of AKT signaling. mTOR is a downstream target which is blocked by RAD-001. The addition of an mTOR inhibitor to EGFR blockade by gefitinib may augment downregulation of AKT. Methods: Nineteen patients with GBM were enrolled in a phase I/II protocol open to patients with either hormone refractory prostate cancer or recurrent GBM. Patients on enzyme inducing anti-epileptic drugs (EIAEDs) were excluded, but prior treatment with an EGFR inhibitor was allowed. All patients received gefitinib 250 mg daily. Two patients enrolled in a dose escalation arm received RAD-001 30 mg or 50 mg weekly; 17 patients received the maximum tolerated dose of RAD-001 70 mg weekly. Baseline and follow-up MRIs were reviewed by a neuro-radiologist. Primary endpoints were radiographic response and progression-free survival (PFS). Results: There were 11 men and 8 women with a median age of 53 years (range 22–72) and median KPS of 80 (range 70–100). Seventeen patients (89%) were treated at their second or greater recurrence. The most frequent grade 1 and 2 toxicities were thrombocytopenia, elevated ALT, rash, anemia, leukopenia, and diarrhea. Grade 3 lymphopenia occurred in 8 patients (42%); two patients (11%) had grade 4 seizures unrelated to the study drugs. Five patients (26%) had a partial radiographic response, including one treated at 3rd recurrence, 2 treated at 4th recurrence, and one who had progressed through prior gefitinib therapy. Two additional patients (11%) had disease stabilization for greater than 4 months. Median PFS was 2.6 months. Median overall survival has not been reached, with a median follow up of 5.4 months for surviving patients. Conclusions: The combination of RAD-001 and gefitinib demonstrated activity in 37% of patients with GBM (26% responded, 11% achieved stable disease). Most subjects were heavily pre-treated and expected to have resistant disease. Because disease control was not durable, alternate dosing, or treatment earlier in the course of disease should be considered in further studying this promising combination. [Table: see text]