Disseminated progression of glioblastoma after treatment with bevacizumab

Reports of glioblastoma (GBM) progression following treatment with bevacizumab indicate that a subset of patients develop disseminated, often minimally enhancing tumors that differ from the typical pattern of focal recurrence. We have reviewed our institutional experience with bevacizumab for GBM to evaluate the prognostic factors and outcomes of patients with disseminated progression.

Medical records of patients treated for GBM at the University of California San Francisco from 2005 to 2009 were reviewed. Patients receiving bevacizumab for focal disease were evaluated and imaging was reviewed to identify patients who progressed in a disseminated pattern. Tumor and treatment factors were compared between focal and disseminated progressors to identify predictive factors for dissemination. Clinical outcomes were compared between progression groups.

Seventy-one patients received adjuvant bevacizumab at some point in their disease course in addition to surgical resection and standard chemoradiotherapy. Of these, 12 patients (17%) had disseminated progression after bevacizumab. There were no differences in patient demographics, surgical treatment, or bevacizumab administration between disseminated and focal progressors. Length of bevacizumab treatment for disseminated progressors trended toward increased time (7.4 vs. 5.4 months) but was not statistically significant (p=0.1). Although progression-free survival and overall survival did not differ significantly between progression groups (median survival from progression was 3.8 vs. 4.6 months, p=0.5), over 30% of focal progressors had a subsequent resection and enrollment in a surgically based clinical trial, whereas none of the disseminated progressors had further surgical intervention. Compared to previously published reports of GBM dissemination with and without prior bevacizumab treatment, our patients had a rate of disease dissemination similar to the baseline rate observed in patients treated without bevacizumab.

The risk of dissemination does not appear to be considerably increased due to the use of bevacizumab, and the pattern of disease at progression does not affect subsequent survival. Therefore, the risk of dissemination should not influence the decision to treat with bevacizumab, especially for recurrent disease.