Effect of alternative temozolomide schedules on glioblastoma O(6)-methylguanine-DNA methyltransferase activity and survival.

BACKGROUND: O(6)-methylguanine-DNA methyltransferase (MGMT) expression in glioblastoma correlates with temozolomide resistance. Dose-intense temozolomide schedules deplete MGMT activity in peripheral blood mononuclear cells; however, no published data exist evaluating the effect of temozolomide schedules on intracranial tumour MGMT activity. METHODS: Human glioblastoma cells (GBM43) with an unmethylated MGMT promoter were implanted intracranially in immunodeficient rodents. Three weeks later, animals received temozolomide 200 mg m(-2) for 5 days (schedule A, standard dose) or 100 mg m(-2) for 21 days (schedule B, dose intense). RESULTS: Tumour MGMT activity was depleted by day 6 in both treatment groups compared with baseline. O(6)-methylguanine-DNA methyltransferase activity returned to baseline by day 22 in the schedule A group, but remained suppressed in the schedule B group. By day 29, MGMT activity had returned to baseline in both groups. Mean tumour volume was significantly decreased compared with untreated controls with either schedule (P<0.01), although neither schedule was superior (P=0.60). Median survival was 64, 42, and 28 days for schedule A, schedule B, and no drug, respectively (P<0.001 A or B vs control, P=NS A vs B). CONCLUSIONS: Dose-intense temozolomide prolongs tumour MGMT activity depletion compared with standard dosing, however, survival was not improved in this model.

Intraoperative high field magnetic resonance imaging in neurosurgery: our initial experience with the brain suite.

We present our initial experience with the high field (1.5T) intra-operative magnetic resonance imaging, the operating room set-up, our initial cases, the difficulties we faced and how this tool affected a change in the surgical strategy intra-operatively and finally our results. 11 patients were operated on from June 1st to August 1st 2006 of which there were astrocytomas (7), pituitary adenoma (1), craniopharyngioma (1) and meningiomas (2) Localization and lesion targeting were accurate, intra-operative imaging helped to assess the resection volumes, enable corrections for brain shift, perform further tumor resection at the same sitting and help preserve eloquent cortical areas. Gliomas formed 63.6% of the tumors operated on and in 71.4% of these, our surgical strategy changed intra-operatively. Meningiomas formed 9.1% of the tumors operated and image guidance enabled a minimally invasive approach, although no change in our surgical plan was required. One pituitary adenoma and a craniopharyngioma were also operated on with good outcome.