A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).

BackgroundOfranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.MethodsThis pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).ResultsEnrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91-1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3-5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction.ConclusionsIn this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results.Clinical trials registrationNCT02511405

ATCT-15CB-018: A PHASE 2 TRIAL OF BEVACIZUMAB PLUS TPI 287, A NOVEL BRAIN PENETRABLE ANTI-MICROTUBULE AGENT, IN PATIENTS WITH RECURRENT GLIOBLASTOMA FOLLOWING PROGRESSION ON ANTI-ANGIOGENIC THERAPY

Bayt Basil is located on Raheb Bahira Street. This eighteenth century house features a well-planted courtyard of lemon and citrus trees and an ornamented iwan that is used as a chapel. The western reception room is covered with a punctuated dome that allows light through. It is currently used as the convent of the Basilian nuns of Aleppo. Source: Hadjar, Abdallah. Historical Monuments of Aleppo. Aleppo: Automobile and Touring Club of Syria (ATCS). 49.interior, view of reception hall dome, 199

Preoperative relative cerebral blood volume analysis in gliomas predicts survival and mitigates risk of biopsy sampling error.

Appropriate management of adult gliomas requires an accurate histopathological diagnosis. However, the heterogeneity of gliomas can lead to misdiagnosis and undergrading, especially with biopsy. We evaluated the role of preoperative relative cerebral blood volume (rCBV) analysis in conjunction with histopathological analysis as a predictor of overall survival and risk of undergrading. We retrospectively identified 146 patients with newly diagnosed gliomas (WHO grade II-IV) that had undergone preoperative MRI with rCBV analysis. We compared overall survival by histopathologically determined WHO tumor grade and by rCBV using Kaplan-Meier survival curves and the Cox proportional hazards model. We also compared preoperative imaging findings and initial histopathological diagnosis in 13 patients who underwent biopsy followed by subsequent resection. Survival curves by WHO grade and rCBV tier similarly separated patients into low, intermediate, and high-risk groups with shorter survival corresponding to higher grade or rCBV tier. The hazard ratio for WHO grade III versus II was 3.91 (p = 0.018) and for grade IV versus II was 11.26 (p \u3c 0.0001) and the hazard ratio for each increase in 1.0 rCBV units was 1.12 (p \u3c 0.002). Additionally, 3 of 13 (23%) patients initially diagnosed by biopsy were upgraded on subsequent resection. Preoperative rCBV was elevated at least one standard deviation above the mean in the 3 upgraded patients, suggestive of undergrading, but not in the ten concordant diagnoses. In conclusion, rCBV can predict overall survival similarly to pathologically determined WHO grade in patients with gliomas. Discordant rCBV analysis and histopathology may help identify patients at higher risk for undergrading