Risk Estimation in Non-Enhancing Glioma: Introducing a Clinical Score

The preoperative grading of non-enhancing glioma (NEG) remains challenging. Herein, we analyzed clinical and magnetic resonance imaging (MRI) features to predict malignancy in NEG according to the 2021 WHO classification and developed a clinical score, facilitating risk estimation. A discovery cohort (2012-2017, n = 72) was analyzed for MRI and clinical features (T2/FLAIR mismatch sign, subventricular zone (SVZ) involvement, tumor volume, growth rate, age, Pignatti score, and symptoms). Despite a "low-grade" appearance on MRI, 81% of patients were classified as WHO grade 3 or 4. Malignancy was then stratified by: (1) WHO grade (WHO grade 2 vs. WHO grade 3 + 4) and (2) molecular criteria (IDH^mut WHO grade 2 + 3 vs. IDH^wt glioblastoma + IDH^mut astrocytoma WHO grade 4). Age, Pignatti score, SVZ involvement, and T2/FLAIR mismatch sign predicted malignancy only when considering molecular criteria, including IDH mutation and CDKN2A/B deletion status. A multivariate regression confirmed age and T2/FLAIR mismatch sign as independent predictors (p = 0.0009; p = 0.011). A "risk estimation in non-enhancing glioma" (RENEG) score was derived and tested in a validation cohort (2018-2019, n = 40), yielding a higher predictive value than the Pignatti score or the T2/FLAIR mismatch sign (AUC of receiver operating characteristics = 0.89). The prevalence of malignant glioma was high in this series of NEGs, supporting an upfront diagnosis and treatment approach. A clinical score with robust test performance was developed that identifies patients at risk for malignancy.