Behavior-Oriented Nomogram for the Stratification of Lower-Grade Gliomas to Improve Individualized Treatment

Abstract

Secondary glioblastomas (sGBM) are derived from previously lower-grade [World Health Organization (WHO) grades II or III] gliomas. Lower-grade benign-behaving gliomas may retain their former grade following recurrence, or may become malignant higher-grade glioblastomas. Prediction of tumor behavior in lower-grade gliomas is critical for individualized glioma therapy. A total of 89 patients were included between January 2000 and January 2019 in the present study to establish a nomogram via univariate and multivariate logistic regression analyses. Nomogram predictive performance was tested in the validation group. We then analyzed 36 O-6-methylguanine-DNA methyltransferase (MGMT) unmethylated lower-grade gliomas from patients seen at West China Hospital of Sichuan University. Survival statistics were calculated with the Kaplan-Meier method. Two clinical factors (molecular diagnosis and WHO grade), five radiological factors (location, cortical involvement, multicentricity, uniformity, and margin enhancement), one biomarker (1p19q codeletion), and a combination of three biomarkers (IDH+/ATRX-/TP53-) were associated with glioma upgrading. Nomograms positive for these prognostic factors had an AUC of 0.880 in the derivation group and 0.857 in the validation group. The calibration and score-stratified survival curves for the derivation group and validation group were good. An operational nomogram was published at https://warrenwrl.shinyapps.io/DynNomapp/. The overall survival of secondary gliomas in the MGMT-unmethylated cohort were influenced independently by the use of temozolomide during the treatment of formerly low-grade gliomas (p=0.00096). Clinical and radiological factors and biomarker-based behavior-oriented nomograms may offer a feasible identification tool for the detection of sGBM precursors. This method may further assist neurosurgeons with the stratification of lower-grade glioma cases and thus the development of better, more individualized treatment plans.