Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas

J Neurooncol. 2024 Mar;167(1):133-144. doi: 10.1007/s11060-024-04585-7. Epub 2024 Feb 7.

Abstract

Background: Isocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown.

Methods: Patients undergoing surgery (between 2016-2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2-3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors.

Results: This multi-center study included 157 patients (mean age 58 years (20-87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response.

Conclusions: WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

Keywords: Extend of resection; Glioblastoma; IDH1/2 wildtype; Prognostic factors; WHO grade II or III astrocytomas.

Publication types

  • Multicenter Study

MeSH terms

  • Astrocytoma* / genetics
  • Astrocytoma* / pathology
  • Astrocytoma* / therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / therapy
  • ErbB Receptors / genetics
  • Female
  • Glioma* / diagnosis
  • Glioma* / genetics
  • Glioma* / therapy
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Retrospective Studies
  • Treatment Outcome
  • World Health Organization

Substances

  • Isocitrate Dehydrogenase
  • ErbB Receptors
  • IDH1 protein, human