Bevacizumab for Patients with Recurrent Gliomas Presenting with a Gliomatosis Cerebri Growth Pattern.

Michael Burger,Marlies Wagner,Iris Mildenberger,Oliver Bähr,Michel Mittelbronn,Joachim Steinbach

doi:10.3390/ijms18040726

Abstract

Bevacizumab has been shown to improve progression-free survival and neurologic function, but failed to improve overall survival in newly diagnosed glioblastoma and at first recurrence. Nonetheless, bevacizumab is widely used in patients with recurrent glioma. However, its use in patients with gliomas showing a gliomatosis cerebri growth pattern is contentious. Due to the marked diffuse and infiltrative growth with less angiogenic tumor growth, it may appear questionable whether bevacizumab can have a therapeutic effect in those patients. However, the development of nodular, necrotic, and/or contrast-enhancing lesions in patients with a gliomatosis cerebri growth pattern is not uncommon and may indicate focal neo-angiogenesis. Therefore, control of growth of these lesions as well as control of edema and reduction of steroid use may be regarded as rationales for the use of bevacizumab in these patients. In this retrospective patient series, we report on 17 patients with primary brain tumors displaying a gliomatosis cerebri growth pattern (including seven glioblastomas, two anaplastic astrocytomas, one anaplastic oligodendroglioma, and seven diffuse astrocytomas). Patients have been treated with bevacizumab alone or in combination with lomustine or irinotecan. Seventeen matched patients treated with bevacizumab for gliomas with a classical growth pattern served as a control cohort. Response rate, progression-free survival, and overall survival were similar in both groups. Based on these results, anti-angiogenic therapy with bevacizumab should also be considered in patients suffering from gliomas with a mainly infiltrative phenotype.

Highlights

Bevacizumab (BEV) is a humanized monoclonal antibody targeting VEGF-A, which is being secreted by malignant gliomas [1]
We were able to confirm the finding of the exploratory post-hoc evaluation of the AVAglio trial that the effect of BEV on progression-free survival (PFS) is similar in patients with gliomatosis-like and non-gliomatosis-like disease in patients with glioblastoma (GBM) [17]
While all patients examined in the AVAglio data were selected patients with GBM qualifying for participation in a therapy study, our data are derived from a much more diverse and heavily pretreated patient group with gliomas WHO◦II-IV

Summary

Introduction

Bevacizumab (BEV) is a humanized monoclonal antibody targeting VEGF-A, which is being secreted by malignant gliomas [1]. VEGF-A induces neovascularization by the formation of a dysfunctional vascular system, and an increase in permeability of the physiologically tight blood–brain barrier [2]. Increased vascular permeability results in pronounced extracellular edema, which is frequently seen in malignant gliomas [3]. By blocking VEGF, neo-angiogenesis is reduced, and the highly abnormal tumor vasculature partially normalizes to a more physiologically condition [4,5]. The peritumoral edema is decreased through the reduction of vascular permeability [6]. In this initial phase, normalization of the highly dysfunctional neovasculature leads to an improvement of tumor perfusion and oxygenation as well [7]. With proceeding regression of tumor vasculature, the supply with oxygen and glucose gets increasingly insufficient [8,9]

Methods

Results

Conclusion