Bevacizumab in Recurrent Glioma: Patterns of Treatment Failure and Implications

Glioblastoma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor receptor, has increasingly been used in the treatment of recurrent glioblastoma. It has achieved excellent rates of radiographic response, but most patients will progress after only a few months. Upon recurrence, tumors may not enhance, secondary to vascular normalization. We describe four patterns of radiographic progression commonly associated with Bevacizumab failure: 1) Distant enhancing tumor, 2) Local tumor progression without enhancement, 3) Diffuse gliomatosis-like infiltration, and 4) Local or multifocal progression, with enhancement. Some have noted an increased incidence of distant or diffuse disease upon recurrence, suggestive of a transition to a more aggressive phenotype, but a review of the literature suggests there is no conclusive evidence that Bevacizumab treatment is associated with an increased rate of distant or diffuse recurrence.