Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial
Introduction - The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 March 2018
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| In: |
European journal of cancer
Year: 2018, Volume: 94, Pages: 168-178 |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2018.02.023 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.ejca.2018.02.023 Verlag: http://www.sciencedirect.com/science/article/pii/S0959804918302302 
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| Author Notes: | Y. Gao, B. Weenink, M.J. van den Bent, L. Erdem-Eraslan, J.M. Kros, PAE Sillevis Smitt, K. Hoang-Xuan, A.A. Brandes, M. Vos, F. Dhermain, R. Enting, G.F. Ryan, O. Chinot, M. Ben Hassel, M.E. van Linde, W.P. Mason, J.M.M. Gijtenbeek, C. Balana, A. von Deimling, Th Gorlia, R. Stupp, M.E. Hegi, B.G. Baumert, P.J. French |
| Summary: | Introduction - The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed gene expression profiling on tissues from this trial to identify markers associated with progression-free survival (PFS) and treatment response. - Methods - Gene expression profiling, performed on 195 samples, was used to assign tumours to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as previously defined using unsupervised expression analysis) and to determine the composition of immune infiltrate. DNA copy number changes were determined using OncoScan arrays. - Results - We confirm that IGSs are prognostic in the EORTC22033-26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards benefit from RT was observed for samples assigned to IGS-9 (hazard ratio [HR] for TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P = 0.62). We did not identify genes significantly associated with PFS within intrinsic subtypes, although follow-up time is limited. We also show that LGGs and glioblastomas differ in their immune infiltrate, which suggests that LGGs are less amenable to checkpoint inhibitor-type immune therapies. Gene expression analysis also allows identification of relatively rare subtypes. Indeed, one patient with a pilocytic astrocytoma was identified. - Conclusion - IGSs are prognostic for PFS in EORTC22033-26033 clinical trial samples. |
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| Item Description: | Gesehen am 13.12.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2018.02.023 |