التفاصيل البيبلوغرافية
| العنوان: |
Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial. |
| المؤلفون: |
Erdem-Eraslan, Lale1, van den Bent, Martin J.1, Hoogstrate, Youri2,3, Naz-Khan, Hina3, Stubbs, Andrew3, van der Spek, Peter3, Böttcher, René2, Ya Gao1, de Wit, Maurice1, Taal, Walter1, Oosterkamp, Hendrika M.2,4, Walenkamp, Annemiek2,5, Beerepoot, Laurens V.2,6, Hanse, Monique C. J.7, Buter, Jan8, Honkoop, Aafke H.9, van der Holt, Bronno10, Vernhout, René M.10, Sillevis Smitt, Peter A. E.1, Kros, Johan M.11 |
| المصدر: |
Cancer Research. 2/1/2016, Vol. 76 Issue 3, p525-534. 11p. |
| مصطلحات موضوعية: |
*GLIOBLASTOMA multiforme treatment, *CANCER relapse, *BEVACIZUMAB, *THERAPEUTIC use of monoclonal antibodies, *CANCER chemotherapy, *GENE expression |
| مستخلص: |
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, paraffinembedded 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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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