Faculty Bibliography

INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely

We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor-A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent 'normalization' after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers

OBJECTIVE: To describe the surgical approaches, the radiographic and clinical outcomes, and the long-term follow-up of patients harboring thalamic pilocytic astrocytomas after radical resection by means of a stereotactic volumetric technique. METHODS: Seventy-two patients with thalamic pilocytic astrocytomas underwent stereotactic volumetric resection by the senior author (PJK) at the Mayo Clinic between 1984 and 1993 (44 patients) and at New York University Medical Center between 1993 and 2005 (28 patients). Patient demographics, presenting symptoms, surgical approaches, neurological outcomes, pathology, initial postoperative status, and long-term clinical and radiographic follow-up were retrospectively reviewed. RESULTS: On preoperative neurological examinations, 54 of the 72 patients had neurological deficits; of these, 48 had hemiparesis. Postoperative imaging demonstrated gross total resection in 58 patients and minimal (<6 mm) residual tumor in 13 patients. Tumor resection was aborted in one patient. On immediate postoperative examination, 16 patients had significant improvements in hemiparesis. Six patients had worsening of a preexisting hemiparesis and one had a new transient postoperative hemiparesis. There was one postoperative death. After 13 to 20 years of follow-up in the Mayo group (mean, 15 +/- 3 yr) and 1 to 13 years of follow-up in the New York University group (mean, 8 +/- 3 yr), 67 patients were recurrence/progression-free, one had tumor recurrence, and three had progression of residual tumor. There were two shunt-related deaths. On long-term neurological follow-up, 27 patients had significant improvements in hemiparesis; one patient with a postoperative worsening of a preexisting hemiparesis remained unchanged. There were no patients with new long-term motor deficits after stereotactic resection. CONCLUSION: Gross total removal of thalamic pilocytic astrocytomas with low morbidity and mortality can be achieved by computer-assisted stereotactic volumetric resection techniques. Gross total resection of these lesions confers a favorable long-term prognosis without adjuvant chemotherapy and/or radiation therapy and leads to the improvement of neurological deficits

OBJECTIVE: We report the incidence and clinical evolution of postoperative deficits and supplementary motor area (SMA) syndrome after volumetric stereotactic resection of glial neoplasms involving the posterior one-third of the superior frontal convolution. We investigated variables that may be associated with the occurrence of SMA syndrome. METHODS: The postoperative clinical status of 27 consecutive patients who underwent resection of SMA gliomas was retrospectively reviewed. Neurological examination results were recorded 1 day, 1 week, 1 month, and 6 months postoperatively. The extent of tumor resection, the percentage of SMA resection, violation of the cingulate gyrus, and operative complications were tabulated. RESULTS: The overall incidence of SMA-related deficits was 26% (7 of 27 patients), with 3 patients having complete SMA syndrome and 4 patients having partial SMA syndrome. Two additional patients (7.5%) had other postoperative deficits, including one with mild facial weakness and one with transient aphasia. The resection of low-grade gliomas was associated with a higher incidence of SMA syndrome, an outcome that likely reflects more complete removal of functional SMA cortex in this subset of patients. Intraoperative monitoring localized the precentral sulcus within the preoperatively defined tumor volume in 6 (22%) of 27 patients, thereby precluding gross total resection. All 27 patients had excellent outcomes at the 6-month follow-up examination. CONCLUSION: When the resection of SMA gliomas is limited to the radiographic tumor boundaries, the incidence and severity of SMA syndrome may be minimized. With the use of these resection parameters, patients with high-grade SMA gliomas are unlikely to experience SMA syndrome. These findings are helpful in the preoperative counseling of patients who are to undergo cytoreductive resection of SMA gliomas