Object The purpose of this study was to validate a new prognostic index for patients with brain metastases. This index, the Graded Prognostic Assessment (GPA), is based on an analysis of 1960 patients whose data were extracted from the Radiation Therapy Oncology Group (RTOG) database. The GPA is based on 4 criteria: age, Karnofsky Performance Scale score, number of brain metastases, and the presence/absence of extracranial metastases. Each of the 4 criteria is given a score of 0, 0.5, or 1.0, so the patient with best prognosis would have a GPA score of 4.0. Methods Between April 2005 and December 2006, 140 eligible patients with brain metastases were treated at the Gamma Knife Center at the University of Minnesota. The GPA score was calculated for each patient, and the score was then correlated with survival. Survival duration was calculated from the date treatment began for the brain metastases. Eligibility criteria included patients treated with whole-brain radiation therapy, stereotactic radiosurgery, or both. Results The median survival time in months observed in the RTOG and Minnesota data by GPA score was as follows: GPA 3.5–4.0, 11.0 and 21.7; GPA 3.0, 8.9 and 17.5; GPA 1.5–2.5, 3.8 and 5.9; and GPA 0–1.0, 2.6 and 3.0, respectively. Conclusions The University of Minnesota data correlate well with the RTOG data and validate the use of the GPA as an effective prognostic index for patients with brain metastases. Clearly, not all patients with brain metastases have the same prognosis, and treatment decisions should be individualized accordingly. The GPA score does appear to be as prognostic as the RPA and is less subjective (because the RPA requires assessment of whether the primary disease is controlled), more quantitative, and easier to use and remember. A multiinstitutional validation study of the GPA is ongoing.

The ability of hemodilution to lower blood viscosity and increase cerebral blood flow has been proven experimentally; however, the optimum hematocrit for maximum oxygen delivery to ischemic brain tissue is not known, and a study was designed to determine this. Fifty dogs were selected for inclusion in the study using criteria based on changes in somatosensory evoked potentials at the time of arterial occlusion, which were found in a previous study to predict the development of a moderate infarction of relatively constant size. Infarctions were induced by permanent occlusion of the left middle cerebral artery and the azygous anterior cerebral artery. The animals selected for inclusion were divided into five groups of 10 dogs each: 1) a control group; 2) a group with 25% hematocrit; 3) a group with 30% hematocrit; 4) a group with 35% hematocrit; and 5) a group with 40% hematocrit. Isovolemic hemodilution was accomplished 1 hour after occlusion of vessels using dextran infusion and blood withdrawal. The animals were sacrificed after 6 days and infarction volume was determined from fluorescein-stained sections. Statistical analysis was performed using Student's t-test and one-way analysis of variance. Mean infarction volume for each group, expressed as a percentage of total hemispheric volume +/- 1 standard error of the mean, was 28.3% +/- 2.8% for the control group, 33.6% +/- 3.4% for the 25% hematocrit group, 17.1% +/- 2.2% for the 30% hematocrit group, 29.2% +/- 4.3% for the 35% hematocrit group, and 29.9% +/- 2.1% for the 40% hematocrit group. The 30% hematocrit group showed the smallest average infarction size and this size differed significantly (p = 0.02) from the average infarction size in the control animals. These results show that, in this model of focal ischemia, a hematocrit of approximately 30% is optimum for protecting the brain.

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To develop a reliable canine model of cerebral infarction of moderate size, we compared infarctions caused by permanent occlusion of the following vessels in 42 dogs: 1) the middle cerebral artery (MCA), 2) the MCA and azygous anterior cerebral artery (ACA), 3) the MCA, azygous ACA, and posterior cerebral artery (PCA), and 4) sham-operated controls. The infarction volume was determined at 6 hours in half the animals and at 6 days in the others. Studies of somatosensory evoked potentials (SSEPs) and regional cerebral blood flow (rCBF) were performed before and after arterial occlusion, and good correlation was observed between the decrease in amplitude of the SSEPs and the decrease in rCBF observed after arterial occlusion. Only the groups in which the MCA and azygous ACA were occluded showed moderate infarctions of relatively consistent size. Analysis involving all groups revealed that the animals with SSEP amplitude preserved after vessel occlusion had only small infarctions; thus, preservation of SSEP amplitude after occlusion of the MCA and azygous ACA could in the future be used prospectively as a rejection criterion to improve the uniformity of infarction size. Conversely, animals with loss of SSEP amplitude after vessel occlusion had infarctions of moderate to large size; thus, loss of SSEP amplitude after MCA occlusion alone could in the future be used prospectively as a rejection criterion. When these rejection criteria were retrospectively applied to the groups in which both the MCA and azygous ACA were occluded, the resulting mean infarction volumes +/- 1 SEM) for the acute and chronic subgroups were 20.3 +/- 2.8% and 38.2 +/- 4.5% of the hemisphere, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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