Introduction: Bevacizumab is an antiangiogenic therapy currently approved for the treatment of recurrent glioblastoma and under investigation as upfront therapy following initial resection. Reports of progression after treatment with bevacizumab demonstrate a subset of patients who developed non-enhancing, diffusely infiltrative tumors that differ from typical focal recurrences. Repeat resection is often not an option due to the extent of disease and undefined boundaries. In this study we review our institutional experience with glioblastoma progression following bevacizumab to evaluate tumor behavior and surgical re-intervention.
Methods: We retrospectively reviewed the medical records of all patients who underwent resection of glioblastoma at our institution from 2005 to 2009, and identified 79 patients who subsequently received bevacizumab. Imaging prior to treatment and at progression was reviewed to determine the nature of progression (focal vs. diffuse). Repeat resection and survival data were obtained from the records. Differences in the rates of repeat resection and survival between tumor phenotypes were compared by univariate analysis.
Results: Tumor progression was documented in 74 patients receiving bevacizumab. Minimally enhancing, diffusely infiltrative tumor progression occurred in 19 patients (26%), with typical enhancing focal progression in 55 patients (74%). Eleven patients received bevacizumab upfront as primary therapy, with 4 patients (36%) developing diffusely infiltrative recurrences. Only 1/19 (5%) with diffusely infiltrative progression underwent repeat resection as compared to 16/55 (29%) focal progressors (p<0.05). Mean survival following progression did not differ significantly between focal and diffuse progressors (21±2 vs. 17±2 wks, p=0.2).
Conclusions: Greater than 25% of patients treated with bevacizumab developed diffusely infiltrative disease at progression, precluding further surgical therapy, including surgically-based clinical trials. Most patients in this study received bevacizumab after recurrence, and therefore survival was limited regardless of progression phenotype. The subset of patients receiving upfront bevacizumab had a 36% rate of diffuse infiltration at progression, restricting re-intervention at first recurrence.
Patient Care: Improved understanding of glioblastoma progression after bevacizumab treatment will improve clinical decision making when choosing a chemotherapeutic regimen for glioblastoma patients.
Learning Objectives: By the conclusion of this session participants should be able to 1) describe the phenotypes for glioblastoma progression after treatment with bevacizumab, 2) discuss the implications of bevacizumab treatment on surgical re-intervention at progression