What are the effects of antiangiogenic therapy for people with high-grade glioma?

2019 ◽  
Author(s):  
Simone Mocellin ◽  
Sera Tort
Author(s):  
Ashwatha Narayana ◽  
Saroj D. Kunnakkat ◽  
Praveen Medabalmi ◽  
John Golfinos ◽  
Erik Parker ◽  
...  

2009 ◽  
Vol 110 (1) ◽  
pp. 173-180 ◽  
Author(s):  
Ashwatha Narayana ◽  
Patrick Kelly ◽  
John Golfinos ◽  
Erik Parker ◽  
Glyn Johnson ◽  
...  

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.


Author(s):  
Mustafa Khasraw ◽  
Malaka S Ameratunga ◽  
Robin Grant ◽  
Helen Wheeler ◽  
Nick Pavlakis

2018 ◽  
Vol 215 (3) ◽  
pp. 963-983 ◽  
Author(s):  
Il-Kug Kim ◽  
Kangsan Kim ◽  
Eunhyeong Lee ◽  
Dong Sun Oh ◽  
Chan Soon Park ◽  
...  

High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has transient clinical benefit in only a fraction of patients. Vascular regulators of these heterogeneous responses remain undetermined. We found up-regulation of Sox7 and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7 deletion suppressed VEGFR2 expression, vascular abnormality, hypoxia-driven invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17 deletion exacerbated these phenotypes by up-regulating Sox7 in tECs. Anti-VEGFR2 antibody treatment delayed tumor growth by normalizing Sox17-deficient abnormal vessels with high Sox7 levels but promoted it by regressing Sox7-deficient vessels, recapitulating variable therapeutic responses to antiangiogenic therapy in HGG patients. Our findings establish that Sox7 promotes tumor growth via vessel abnormalization, and its level determines the therapeutic outcome of VEGFR2 inhibition in HGG. In 189 HGG patients, Sox7 expression was heterogeneous in tumor vessels, and high Sox7 levels correlated with poor survival, early recurrence, and impaired vascular function, emphasizing the clinical relevance of Sox7 in HGG.


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