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

Eur J Cancer. 2018 May;94:168-178. doi: 10.1016/j.ejca.2018.02.023. Epub 2018 Mar 20.


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.

Keywords: BELOB; Gene expression profiling; Immunophenotype; Intrinsic subtype; Low grade glioma; Pilocytic astrocytoma.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy
  • Female
  • Glioma / genetics
  • Glioma / pathology*
  • Glioma / therapy
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Progression-Free Survival
  • Temozolomide / therapeutic use
  • Transcriptome*
  • Treatment Outcome


  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Temozolomide

Associated data