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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2024年2月7日

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  • Naureen Keric,
  • Harald Krenzlin,
  • Darius Kalasauskas,
  • Christian F. Freyschlag,
  • Oliver Schnell,
  • Martin Misch,
  • Christian von der Brelie,
  • Jens Gempt,
  • Aleksandrs Krigers,
  • Arthur Wagner,
  • Felipa Lange,
  • Dorothee Mielke,
  • Clemens Sommer,
  • Marc A. Brockmann,
  • Bernhard Meyer,
  • Veit Rohde,
  • Peter Vajkoczy,
  • Jürgen Beck,
  • Claudius Thomé,
  • Florian Ringel

摘要

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.