Faculty Bibliography

An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent "sham radiosurgery." All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20-Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted.

The challenges associated with microsurgery of vascular malformations located in the midbrain, pons and medulla have promoted the development of alternative therapeutic techniques. To assess the efficacy and safety of radiosurgery in the management of brain stem vascular malformations we reviewed our 5-year experience in 50 patients evaluated between 4 and 51 months (mean, 25 months) after radiosurgery. Twenty-eight patients (56%) underwent gamma unit radiosurgery for symptomatic arteriovenous malformations (AVMs), and 22 patients (44%) for angiographically occult vascular malformations (AOVMs). Patients varied in age from 7 to 76 years (mean, 39 years). Forty-one patients (82%) had from 1 to 5 hemorrhages prior to gamma knife radiosurgery. Ten (20%) had one or two prior unsuccessful operations, and 37 (74%) presented with a neurological deficit. Of the patients with AVMs, 6 were considered Spetzler Grade III, and 22 (79%) Grade VI (inoperable: major component within the brain stem parenchyma). Forty-four malformations (88%) were adjacent to or within the midbrain and pons; the remainder involved the medulla. Average malformation diameters varied from 6 to 30.4 m (mean, 20.6; mean volume 4614 mm3). The minimal radiation dose to the margin of the malformations ranged from 12 to 25.6 Gy (mean, 18.9 Gy). Of the 28 patients with AVMs, 8 had follow-up angiograms at a minimum of 2-years after radiosurgery (or sooner if their MRIs suggested obliteration). Of these patients, 7 (88%) showed complete obliteration of their malformations. No patients with AOVMs rehemorrhaged if more than 15 months elapsed after radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)