Rapid Diagnosis of Adult-type Diffuse Glioma using a Layered Scheme

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 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 define a novel layered diagnostic scheme for adult-type diffuse gliomas with the detection of IDH and TERT promoter (TERTp) mutations as the first layer. Moreover, we develop a technology for rapid intraoperative testing of TERTp and IDH mutations within 35 mins. A retrospective cohort and a prospective multicenter diagnostic test were involved in. The diagnostic accuracy of the layered diagnostic scheme was measured via sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) with a 95% confidence interval. Results In retrospective cohort, the TERTp mutation displayed a similar statistical power as 1p/19q in distinguishing oligodendrogliomas from astrocytomas (kappa = 0.96, P < 0.001). In addition, 91.8% of all the glioblastomas with either EGFRamp or + 7/-10 had TERTp mutations. Moreover, prospective application of the layered diagnostic scheme and the rapid testing, 223 gliomas and 2 non-gliomas (76.5%) were classified accurately intraoperatively. With the assistance of the postoperative permanent section, 249 gliomas and 24 non-gliomas (92.9%) were accurately classified after detecting the first layer biomarkers. Conclusions The layered diagnostic scheme provides rapid and accurate integrated diagnoses of adult-type diffuse gliomas, facilitates the broader use of molecular classification, and expands its application from postoperatively to intraoperatively for most patients.