Introduction: Though bevacizumab is often used to treat high grade glioma, a subgroup of patients with unknown characteristics will develop significantly invasive tumors following treatment, leading to catastrophic failure. We initiated a study to analyze whether specific molecular subgroups of glioblastoma (GBM) are more likely to develop this invasive phenotype.
Methods: Patients with GBM treated with bevacizumab at Memorial Sloan-Kettering between 2008 and 2012 and whose tumors had been profiled for TCGA class by our Tumor Bank were identified. Forty-eight patients were identified who also had pre and post-bevacizumab treatment MRIs available for review. Of these patients, 27 had proneural tumors, 10 had classical tumors, 9 had mesenchymal tumors, and 2 had both classical and mesenchymal features. MRIs before and after treatment were evaluated for changes in enhancement, multifocal change, extent of FLAIR signal, and pattern of tumor extension (focal, diffuse, bihemispheric).
Results: We identified 16.66% of patients whose post-treatment MRI looked extensively worse than their pre-treatment MRI by any criteria. The percent of patients with worse overall post-treatment MRI was significantly higher in the mesenchymal and mesenchymal/classical groups than the proneural and classical groups (44.4% and 50% vs 7.4 and 10%, respectively, p=.04). There was no statistically significant difference in change in enhancement, multifocal change, change in FLAIR, focal to diffuse change, or bihemispheric change among patients of different TCGA subtype. Among patients with the worse MRI change, worsened enhancement, multifocal change, and focal to diffuse change were the most statistically significant (p<.01, <.001, and .02, respectively).
Conclusions: Our data confirm that a subgroup of patients experience dramatic worsening post-bevacizumab treatment and suggest that the mesenchymal subgroup is at highest risk of experiencing fulminant progression following treatment. Ongoing work will extend our observations to a larger group of patients and will include more extensive molecular data.
Patient Care: This research suggests that bevacizumab may be more safely used in non-mesenchymal subgroups of GBM.
Learning Objectives: By the conclusion of the session, participants should be able to:
1) Describe patterns of worsening of tumor on MRI.
2) Identify the subgroup of patients at greatest risk of failure after bevacizumab treatment
3) Understand the risk of progression for different subgroups after bevacizumab treatment