Early Postoperative Treatment versus Initial Observation in CNS WHO Grade 2 and 3 Oligodendroglioma: Clinical Outcomes and DNA Methylation Patterns

Clin Cancer Res. 2022 Oct 14;28(20):4565-4573. doi: 10.1158/1078-0432.CCR-22-1133.

Abstract

Purpose: The treatment of oligodendroglioma consists of tumor resection and radiochemotherapy. The timing of radiochemotherapy remains unclear, and predictive biomarkers are limited.

Experimental design: Adult patients diagnosed with isocitrate dehydrogenase (IDH)-mutated, 1p/19q-codeleted CNS WHO grade 2 and 3 oligodendroglioma at the Medical University of Vienna and the Kepler University Hospital Linz (Austria) in 1992 to 2019 were included. Progression-free (PFS) and overall survival (OS) between early postoperative treatment and initial observation were compared using propensity score-weighted Cox regression models. DNA methylation analysis of tumor tissue was performed using Illumina MethylationEPIC 850k microarrays.

Results: One hundred thirty-one out of 201 (65.2%) patients with CNS WHO grade 2 and 70 of 201 (34.8%) with grade 3 oligodendroglioma were identified. Eighty-three of 201 (41.3%) patients underwent early postoperative treatment, of whom 56 of 83 (67.5%) received radiochemotherapy, 15 of 84 (18.1%) radiotherapy (RT) only and 12 of 83 (14.5%) chemotherapy only. Temozolomide-based treatment was administered to 64 of 68 (94.1%) patients, whereas RT + procarbazine, lomustine (CCNU), and vincristine (PCV) were applied in 2 of 69 (3.5%) patients. Early treatment was not associated with PFS [adjusted hazard ratio (HR) 0.74; 95% CI, 0.33-1.65, P = 0.459] or OS (adjusted HR: 2.07; 95% CI, 0.52-8.21, P = 0.302) improvement. Unsupervised clustering analysis of DNA methylation profiles from patients receiving early treatment revealed two methylation clusters correlating with PFS, whereas no association of clustering with O6-methylguanine methyltransferase (MGMT) promoter methylation, CNS WHO grade, extent of resection, and treating center could be observed.

Conclusions: In this retrospective study, early postoperative treatment was not associated with improved PFS/OS in oligodendroglioma. The potentially predictive value of whole-genome methylation profiling should be validated in prospective trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / therapy
  • DNA Methylation
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Lomustine
  • Methyltransferases / genetics
  • Oligodendroglioma* / genetics
  • Oligodendroglioma* / surgery
  • Procarbazine / therapeutic use
  • Prospective Studies
  • Retrospective Studies
  • Temozolomide / therapeutic use
  • Vincristine
  • World Health Organization

Substances

  • Procarbazine
  • Vincristine
  • Lomustine
  • Isocitrate Dehydrogenase
  • Methyltransferases
  • Temozolomide