Prognostic implication of progression pattern after anti-VEGF bevacizumab treatment for recurrent malignant gliomas

Malignant glioma treated with anti-vascular endothelial growth factor (VEGF) bevacizumab show progression patterns that vary with different mechanisms of resistance. We evaluated the clinico-radiological data of 71 patients with progressive malignant glioma treated with bevacizumab to determine the prognostic value of the differential outcome of each progression pattern. Progression patterns were categorized as three types based on the initial response to bevacizumab and serious changes of MR images i.e., non-enhancing infiltration, flare-up of contrast enhancement (CE) and primary non-responder progression. We analyzed the clinical outcome in each type of progression using Kaplan-Meier survival analysis. Analysis of progression patterns showed that incidence of non-enhancing infiltration progression (28.1 %) was less common than flare-up of CE or primary non-responder pattern. The time from initiation of bevacizumab to development of non-enhancing infiltration or flare-up of CE progression was longer than for progression in primary non-responders. There was no significant difference of overall survival, progression-free survival from start of bevacizumab therapy, survival after bevacizumab failure between non-enhancing infiltration and flare-up of CE patterns. However, in the non-enhancing infiltration pattern, early appearance of enhancement was observed after bevacizumab was discontinued, resulting in poor survival, as compared to flare-up of CE pattern (P = 0.01). Although the appearance of non-enhancing infiltration after bevacizumab does not imply a worse prognosis, discontinuation of therapy can aggravate the clinical course.