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

in BMC medicine by Jinsong Wu, Shuai Wu, Dandan Cao, Zhang Xiong, Jianhua Zhang, Yourui Zou, Zanyi Wu, Yanli Nie, Chen Luo, Ye Yao, Yanyan Song, Yuchen Jiao, Hong Chen, Hui Ma, Dezhi Kang, Ying Mao, Hai Yan

TLDR

  • The study proposes a novel layered diagnostic scheme for adult-type diffuse gliomas, starting with IDH and TERTp mutation detection, which improves diagnostic accuracy.

Abstract

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. 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. 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. 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. ClinicalTrials.gov NCT04924127, NCT04904419.

Overview

  • The study aimed to investigate the role of IDH and TERTp mutations in the diagnosis of adult-type diffuse glioma.
  • The researchers proposed a novel layered diagnostic scheme, starting with IDH and TERTp mutation detection, to improve diagnosis.
  • The study included a retrospective cohort and a prospective multicenter diagnostic test to evaluate the diagnostic accuracy of the layered approach.

Comparative Analysis & Findings

  • The study found that TERTp mutation demonstrated comparable statistical power to 1p/19q codeletion in distinguishing oligodendrogliomas from astrocytomas.
  • Ninety-one percent of glioblastomas with either EGFR amplification or +7/-10 exhibited TERTp mutations.
  • The layered diagnostic scheme demonstrated high accuracy, with 92.9% of gliomas and non-gliomas correctly classified following the detection of the first-layer biomarkers.

Implications and Future Directions

  • The proposed layered diagnostic scheme can facilitate the broader use of molecular classification in clinical practice.
  • The rapid intraoperative testing technology can enhance diagnostic efficiency and accuracy.
  • Future studies can focus on further validation and refinement of the layered diagnostic scheme, as well as exploration of its applicability to other types of gliomas.
Read Full Article