학술논문
Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial.
Document Type
Academic Journal
Author
Erdem-Eraslan L; Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; van den Bent MJ; Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Hoogstrate Y; Department of Urology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Bioinformatics, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Naz-Khan H; Bioinformatics, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Stubbs A; Bioinformatics, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; van der Spek P; Bioinformatics, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Böttcher R; Department of Urology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Gao Y; Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; de Wit M; Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Taal W; Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Oosterkamp HM; Department of Medical Oncology, Medical Center Haaglanden, The Hague, the Netherlands.; Walenkamp A; Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands.; Beerepoot LV; Department of Oncology, St Elisabeth Ziekenhuis, Tilburg, the Netherlands.; Hanse MC; Department of Neurology, Catharina Hospital Eindhoven, the Netherlands.; Buter J; Department of Oncology, VU University Medical Center, Amsterdam, the Netherlands.; Honkoop AH; Department of Internal Medicine, Isala Kliniek, Zwolle, the Netherlands.; van der Holt B; Clinical Trial Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Vernhout RM; Clinical Trial Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Sillevis Smitt PA; Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Kros JM; Pathology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; French PJ; Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. p.french@erasmusmc.nl.
Source
Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE
Subject
Language
English
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 patients with recurrent glioblastoma (GBM). In this study, we performed gene expression profiling (DASL and RNA-seq) of formalin-fixed, paraffin-embedded tumor material from participants of the BELOB trial to identify patients with recurrent GBM who benefitted most from beva+CCNU treatment. We demonstrate that tumors assigned to the IGS-18 or "classical" subtype and treated with beva+CCNU showed a significant benefit in progression-free survival and a trend toward benefit in overall survival, whereas other subtypes did not exhibit such benefit. In particular, expression of FMO4 and OSBPL3 was associated with treatment response. Importantly, the improved outcome in the beva+CCNU treatment arm was not explained by an uneven distribution of prognostically favorable subtypes as all molecular glioma subtypes were evenly distributed along the different study arms. The RNA-seq analysis also highlighted genetic alterations, including mutations, gene fusions, and copy number changes, within this well-defined cohort of tumors that may serve as useful predictive or prognostic biomarkers of patient outcome. Further validation of the identified molecular markers may enable the future stratification of recurrent GBM patients into appropriate treatment regimens.
(©2016 American Association for Cancer Research.)
(©2016 American Association for Cancer Research.)