Faculty Bibliography

BACKGROUND: The objective of this study was 2-fold: (1) document the presence and degree of vascularity in gliomas of different pathologic grades and (2) determine whether the presence of abnormal vascularity, determined by catheter angiography, correlates with a shortened survival. METHODS: As part of a protocol for radiographic data acquisition that was used in a computer-assisted, stereotactic system, all patients who underwent biopsy or resection of a newly diagnosed glioma between 1994 and 2000 at our institution routinely underwent preoperative catheter angiography. The presence and degree of tumor vascularity were recorded and then correlated with survival and pathologic grade. The confounding effects of age, KPS, adjuvant treatment, and extent of resection on survival were considered. RESULTS: Two hundred thirty-one patients were included in this study. The mean follow-up of survivors was 7.8 years. Tumor vascularity correlated with a shortened survival (proportional hazards RR for survival, 0.69; 95% CI, 0.58-0.82). This correlation persisted after correction for age, KPS score, adjuvant therapy, and extent of resection (RR, 0.81; 95% CI, 0.68-0.97). Abnormal vascularity was present in 25 (30%) of 82 low-grade (WHO grade 2) gliomas. Overall, the extent of vascularity (none [120 patients, 52%], blush [63 patients, 27%], neovessels [25 patients, 11%], and arteriovenous shunting [23 patients, 10%]) correlated with worse WHO tumor grade (P < .0001). CONCLUSIONS: The presence of abnormal vascularity correlates with both a shortened survival and higher grade of malignancy. These findings underscore the importance of antiangiogenesis factor investigation and drug development for the treatment of gliomas, regardless of their pathologic grade

PURPOSE: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2. The lack of effective treatments for NF2 marks an unmet medical need. EXPERIMENTAL DESIGN: Here, we provide recommendations from a workshop, cochaired by Drs. D. Gareth Evans and Marco Giovannini, of 36 international researchers, physicians, representatives of the biotechnology industry, and patient advocates on how to accelerate progress toward NF2 clinical trials. RESULTS: Workshop participants reached a consensus that, based on current knowledge, the time is right to plan and implement NF2 clinical trials. Obstacles impeding NF2 clinical trials and how to address them were discussed, as well as the candidate therapeutic pipeline for NF2. CONCLUSIONS: Both phase 0 and phase II NF2 trials are near-term options for NF2 clinical trials. The number of NF2 patients in the population remains limited, and successful recruitment will require ongoing collaboration efforts between NF2 clinics

Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1-19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1-7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3-7.7) and 9 (95% CI 7.6-10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored

OBJECTIVES: To date, numerous studies have compared functional outcomes between stereotactic radiosurgery (SRS) and microsurgery (MS) in the treatment of vestibular schwannomas (VS). However, most of them involve tumors of difference sizes, radiation dosages, and surgical approaches. Few have systematically compared issues of dysequilibrium. By studying only patients with small tumors and no hearing, we sought to minimize confounding variables. STUDY DESIGN: A retrospective chart review and telephone questionnaire. METHODS: From 1998-2006, 31 patients with small (<1.5 cm) VS and nonserviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] Class C or D) were treated at our institution. Twenty-two were available for follow-up and telephone questionnaire, including the University of California Los Angeles Dizziness Questionnaire (UCLA-DQ). Twelve underwent SRS and 10 underwent MS. All MS patients underwent the translabyrinthine approach to their tumors. Outcomes measurements included tumor control, facial nerve function, tinnitus, trigeminal function, and imbalance. RESULTS: Patients undergoing SRS had comparable rates of tumor control, facial nerve function, tinnitus, and trigeminal function to MS patients. However, SRS did result in statistically significantly worse long-term imbalance when compared with MS patients. Detailed comparisons of the two modalities are made. CONCLUSIONS: In our study population, patients with small tumors and no serviceable hearing, these data suggest that MS results in comparable minimal morbidity with SRS, though posttreatment dysequilibrium is significantly decreased. While the authors recommend translabyrinthine resection of small VS with no hearing in patients able to tolerate surgery, the need for further prospective investigation is clear

OBJECTIVE AND IMPORTANCE: In rare cases, posterior fossa meningiomas can involve the endolymphatic sac. Such involvement can result in endolymphatic hydrops and a constellation of symptoms suggestive of Meniere's disease. The diagnosis and management of patients with these tumors is discussed. CLINICAL PRESENTATION: Three patients, each of whom presented with symptoms consistent with Meniere's disease, were found to have posterior fossa meningiomas limited to the dura overlying the endolymphatic sac. INTERVENTION: All 3 patients were diagnosed by magnetic resonance imaging and underwent complete surgical resection. In all cases, the symptoms resolved after tumor removal. CONCLUSION: Clinicians should have a degree of suspicion of posterior fossa meningioma when patients present with symptoms suggestive of Meniere's disease. Failure to do so may result in delayed diagnosis or worse outcomes for an otherwise treatable tumor

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