Identification of recurrent GBM patients that may benefit from Bevacizumab and CCNU: A report from the BELOB trial by the Dutch Neurooncology Group
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ABSTRACT: The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva; a humanized monoclonal antibody against circulating VEGF-A) when added to CCNU chemotherapy in recurrent GBM patients. In this study, we have performed gene expression profiling (DASL and RNA-seq) on formalin fixed, paraffin embedded (FFPE) tumor material from patients treated within the BELOB trial to identify recurrent GBM patients who benefit most from combined beva/CCNU treatment. We first extensively validate the use of FFPE tissues for expression profiling on both DASL and RNA-seq. Our data show that tumors assigned to IGS-18 or ‘classical’ GBMs show a significant benefit in progression free survival (PFS) and a trend towards benefit in overall survival (OS) from beva+CCNU treatment; other subtypes do not show such benefit. In particular, expression of FMO4 and OSBPL3 were associated with treatment response. All molecular glioma subtypes are evenly distributed along the different study arms and the improved outcome in the beva/CCNU arm therefore is not explained by an uneven distribution of prognostically favorable subtypes. Analysis of RNA-seq data highlighted genetic changes, including mutations, gene fusions (and identification of the exact genomic breakpoint), and copy number changes (albeit with limited resolution) within this well-defined cohort of tumors. When validated in an independent dataset, the predictive markers identified in this study will allow selection of recurrent GBM patients that benefit from beva+CCNU treatment.
ORGANISM(S): Homo sapiens
PROVIDER: GSE72951 | GEO | 2016/01/19
SECONDARY ACCESSION(S): PRJNA295398
REPOSITORIES: GEO
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