Rapid diagnosis of adult-type diffuse glioma using a layered scheme

Abstract

Abstract Background Molecular biomarkers have become an essential part of the diagnosis of adult-type diffuse glioma. Still, complex detection methods and long-term turnaround for these biomarkers hinder integrated diagnosis in clinical practice. We hypothesized that IDH and TERT promoter (TERTp) mutations play similar roles in accurately classifying adult-type diffuse glioma compared to the complicated WHO CNS5-recommended biomarkers, and the detection of IDH and TERTp mutations should be the first layer in clinical practice. Methods We propose a novel layered diagnostic scheme for adult-type diffuse gliomas, with IDH and TERTp mutation detection as the initial layer. We also developed a rapid intraoperative testing technology capable of detecting TERTp and IDH mutations within 35 min. This study involved both a retrospective cohort and a prospective multicenter diagnostic test. The diagnostic accuracy of the layered approach was evaluated using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), with a 95% confidence interval. Results In retrospective cohort, the TERTp mutation demonstrated comparable statistical power to 1p/19q codeletion in distinguishing oligodendrogliomas from astrocytomas (κ = 0.96, P < 0.001). Additionally, 91.8% of glioblastomas with either EGFR amplification or + 7/-10 exhibited TERTp mutations. In the prospective application of the layered diagnostic scheme and rapid testing, 223 gliomas and 2 non-gliomas (76.5%) were accurately classified intraoperatively. With the addition of postoperative permanent section analysis, 249 gliomas and 24 non-gliomas (92.9%) were correctly classified following the detection of the first-layer biomarkers. Conclusions The proposed layered diagnostic scheme offers a rapid and accurate means of classifying adult-type diffuse gliomas, facilitating the broader use of molecular classification. It expands its applicability from postoperative to intraoperative settings for the majority of patients, enhancing diagnostic efficiency and accuracy. Trial registration ClinicalTrials.gov NCT04924127, NCT04904419.

Keywords

• Layered diagnostic scheme
• Adult-type diffuse gliomas
• IDH mutation
• TERT promoter mutation
• Intraoperative integrated diagnosis