Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial

Y. Gao, B. Weenink, M. J. van den Bent, L. Erdem-Eraslan, J. M. Kros, P. A.E. 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 GorliaR. Stupp, M. E. Hegi, B. G. Baumert, P. J. French*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)168-178
Number of pages11
JournalEuropean Journal of Cancer
Volume94
DOIs
StatePublished - May 2018

Keywords

  • BELOB
  • Gene expression profiling
  • Immunophenotype
  • Intrinsic subtype
  • Low grade glioma
  • Pilocytic astrocytoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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