WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas

Area of Science:

• Neuro-oncology
• Molecular diagnostics
• Cancer prognostication

Background:

• Established prognostic factors for diffuse lower-grade glioma (dLGG) largely predate molecular classification.
• The prognostic value of World Health Organization (WHO) grade in IDH-mutant dLGG requires re-evaluation.
• This study investigates the role of traditional prognostic factors in the context of molecularly defined dLGG subgroups.

Purpose of the Study:

• To assess the prognostic significance of WHO grade in molecularly classified dLGG.
• To evaluate the relevance of previously used prognostic factors in the current molecular landscape.
• To determine reliable prognostic markers for IDH-mutant dLGG.

Main Methods:

• Analysis of 253 adult patients with morphological dLGG diagnosed between 2007 and 2018.
• Molecular analysis included IDH mutations, 1p/19q codeletion, and CDKN2A/B deletions.
• Statistical methods included log-rank tests and multivariable analyses to assess prognostic factors.

Main Results:

• WHO grade 2 and 3 showed no significant survival difference in IDH-mutant dLGG without CDKN2A/B deletion.
• Residual tumor volume was prognostic in IDH-mutant astrocytomas but not oligodendrogliomas.
• Preoperative tumor size independently predicted survival in both astrocytomas and oligodendrogliomas.

Conclusions:

• WHO grade is not a robust prognostic factor for molecularly defined IDH-mutant dLGG.
• Preoperative tumor size is a consistent prognostic indicator across IDH-mutant astrocytomas and oligodendrogliomas.
• Traditional age-based risk stratification for IDH-mutant dLGG is not supported by current molecular data.