Faculty Bibliography

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

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

BACKGROUND: The perioperative course of patients undergoing intracranial surgery is frequently complicated by hypertensive episodes. Dexmedetomidine (DEX), an alpha-2 adrenoreceptor agonist, is gaining popularity in neuroanesthesia, because its sympatholytic and antinociceptive properties may improve hemodynamic stability at critical moments of surgery. We designed this study to assess the efficacy of DEX in controlling hypertensive responses in patients undergoing intracranial surgery. METHODS: Patients scheduled for elective craniotomy were randomly assigned to receive either sevoflurane-opioid or sevoflurane-opioid-DEX anesthesia. Bispectral index was used to maintain a similar level of hypnosis in both groups (40-50). Opioids, sevoflurane, and vasoactive medications were titrated in a routine manner, at the discretion of the blinded anesthesiologist managing the case, to maintain systolic blood pressure (SBP) targeted within 90-130 mm Hg and heart rate (HR) between 50 and 90 bpm. Hemodynamic variables were continuously recorded and stored on a computer for analysis. Efficacy of the anesthetic technique in controlling SBP or HR is inversely proportional to the area under the curve (AUC) outside the targeted range. Areas under the curves above and below targeted ranges for SBP-time (AUCsbp mm Hg*min/h) and HR-time (bpm*min/h) were compared. Coefficient of variation was used to assess hemodynamic stability. RESULTS: Seventy-two patients were recruited for the study. Computerized records of 56 patients only were analyzed because of technical problems with data collection in 14 cases. AUCsbp for above the targeted range was significantly lower for patients in the DEX group (P=0.044). The coefficient of variation for SBP or HR did not differ between groups. A significantly smaller proportion of patients in the DEX group required treatment with antihypertensive medications (12 of 28, 42% vs 24 of 28, 86%, P=0.0008). The DEX group required fewer opioids in the intraoperative period, but there were no differences in the use of sevoflurane. In the postanesthesia care unit, patients in the DEX group had fewer hypertensive episodes (1.25+/-1.55 vs 2.50+/-2.00, P=0.0114) and were discharged earlier (91+/-17 vs 130+/-27 min, P<0.0001). There were no differences in the requirement for postoperative opioids or antiemetics. CONCLUSIONS: By using indices, which assess a global hemodynamic stability of the anesthetic, we determined that intraoperative DEX infusion was effective for blunting the increases in SBP perioperatively. The use of DEX did not increase the incidence of hypotension or bradycardia, common side effects of the drug