[en] Purpose/Objective: Radiosurgery is capable of delivering a high, single focused beam of radiation to a small targeted area of defined intracranial lesions. BCNU and cis-platinum have been shown to enhance the radiation induced cell killing. We hypothesized that there may be a window of the time when the drug administered, which would cause preferential accumulation into the tumor tissues relative to the adjacent normal tissues. We have carried out in vivo studies using a 9L glioma rat brain tumor model to determine whether an improved therapeutic efficacy would be obtained by investigating time and sequence of the combined therapy. Materials and Methods: We stereotaxically implanted the brain tissue of male Fischer 344 rats with 9L gliosarcoma cells; within 6 sets of four, by one day, sequentially (3 sets for BCNU and Carboplatin each). Each set then received one of three specific treatment arms. These consisted of either a single high dose of focal photon irradiation at 25 Gy; a single dose of BCNU (7 mg/kg) 1.5 hours prior to a single high dose of photon irradiation (25 Gy); or a single dose of BCNU (7 mg/kg) at 16 hours prior to irradiation. For carboplatin, the drug (30 mg/kg) was administered either 1 hour or 4 hours prior to irradiation. Radiosurgery treatments were delivered with a Cobalt-60 teletherapy unit, a customized linear collimator, and an adapted stereotactic fixating device. The end points for evaluation include % survivals and median survival time of the irradiated brain. The normal tissue effects were evaluated with various histopathology including neuron, myelin and vascular effects. Results: The radiation alone group showed a dose dependent survival. The median survival time of rats with 12 day old 9L tumor without RT was 30 days, 42 days with 25 Gy. In contrast, up to 84 days post implantation, 75% of subjects who received BCNU 1.5 hours before irradiation were alive, with a stable body weight. All rats within the combined treatment groups did not demonstrate any significant toxicity or radiation related side effects. The animals will be followed until final absolute survival results can be completed. Conclusions: Our results indicate there is a significant initial survival advantage to those animal groups receiving time sequenced dose of BCNU prior to their radiosurgery treatment compared to the control groups. Studies are in progress to determine the differential cytotoxic effects of the time sequence variations, and long term effects of critical normal tissues including optic nerves