Bevacizumab treatment for meningiomas in NF2: a retrospective analysis of 15 patients

Fabio P Nunes, Vanessa L Merker, Dominique Jennings, Paul A Caruso, Emmanuelle di Tomaso, Alona Muzikansky, Fred G Barker 2nd, Anat Stemmer-Rachamimov, Scott R Plotkin, Fabio P Nunes, Vanessa L Merker, Dominique Jennings, Paul A Caruso, Emmanuelle di Tomaso, Alona Muzikansky, Fred G Barker 2nd, Anat Stemmer-Rachamimov, Scott R Plotkin

Abstract

Bevacizumab treatment can result in tumor shrinkage of progressive vestibular schwannomas in some neurofibromatosis 2 (NF2) patients but its effect on meningiomas has not been defined. To determine the clinical activity of bevacizumab against NF2-related meningiomas, we measured changes in volume of meningiomas in NF2 patients who received bevacizumab for treatment of progressive vestibular schwannomas. A radiographic response was defined as a 20% decrease in tumor size by volumetric MRI analysis. In addition, we determined the expression pattern of growth factors associated with tumor angiogenesis in paraffin-embedded tissues from 26 unrelated meningiomas. A total of 48 meningiomas in 15 NF2 patients were included in this study with a median follow up time of 18 months. A volumetric radiographic response was seen in 29% of the meningiomas (14/48). Tumor shrinkage was not durable: the median duration of response was 3.7 months and the median time to progression was 15 months. There was no significant correlation between pre-treatment growth rate and meningioma response in regression models. Tissue analysis showed no correlation between tumor microvascular density and expression of VEGF pathway components. This data suggests that, in contrast to schwannomas, activation of VEGF pathway is not the primary driver of angiogenesis in meningiomas. Our results suggest that a minority of NF2-associated meningiomas shrink during bevacizumab therapy and that these responses were of short duration. These results are comparable to previous studies of bevacizumab in sporadic meningiomas.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Radiographic Response of Meningiomas to…
Figure 1. Radiographic Response of Meningiomas to Bevacizumab.
Waterfall plot of best radiographic response for individual meningiomas (A) and for total meningioma volume in patients (B).
Figure 2. Time to Progression for Meningioma…
Figure 2. Time to Progression for Meningioma Treated with Bevacizumab.
A. Kaplan-Meier curve for time to progression considering each meningioma as an independent event (per-tumor analysis). Progression was considered as an increase in tumor volume of 20% or more. B. Kaplan-Meier curve for time to progression using total intracranial meningioma volume for each patient as an independent event (per-patient analysis). Time to progression was 15 months for individual tumors and 20 months on per-patient analysis. Progression-free rate at six months was higher in the per-patient analysis at 93%, compared to 85% for the per-tumor analysis.
Figure 3. Meningioma Best Response Compared to…
Figure 3. Meningioma Best Response Compared to Pre-treatment Growth Rate.
Scatter-plot of meningioma best response vs. relative change in tumor volume prior to treatment. Horizontal dashed lines show threshold for radiographic response at 20% decrease in tumor volume post treatment, and vertical dashed line separates tumors with positive growth prior to therapy.

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