Abstract

The detection of mutations in telomerase reverse transcriptase promoter (pTERT) is important since preoperative diagnosis of pTERT status helps with evaluating prognosis and determining the surgical strategy. Here, we aimed to establish a radiomics-based machine-learning algorithm and evaluated its performance with regard to the prediction of mutations in pTERT in patients with World Health Organization (WHO) grade II gliomas. In total, 164 patients with WHO grade II gliomas were enrolled in this retrospective study. We extracted a total of 1,293 radiomics features from multi-parametric magnetic resonance imaging scans. Elastic net (used for feature selection) and support vector machine with linear kernel were applied in nested 10-fold cross-validation loops. The predictive model was evaluated by receiver operating characteristic and precision-recall analyses. We performed an unpaired t-test to compare the posterior predictive probabilities among patients with differing pTERT statuses. We selected 12 valuable radiomics features using nested 10-fold cross-validation loops. The area under the curve (AUC) was 0.8446 (95% confidence interval [CI], 0.7735–0.9065) with an optimal summed value of sensitivity of 0.9355 (95% CI, 0.8802–0.9788) and specificity of 0.6197 (95% CI, 0.5071–0.7371). The overall accuracy was 0.7988 (95% CI, 0.7378–0.8598). The F1-score was 0.8406 (95% CI, 0.7684–0.902) with an optimal precision of 0.7632 (95% CI, 0.6818–0.8364) and recall of 0.9355 (95% CI, 0.8802–0.9788). Posterior probabilities of pTERT mutations were significantly different between patients with wild-type and mutant TERT promoters. Our findings suggest that a radiomics analysis with a machine-learning algorithm can be useful for predicting pTERT status in patients with WHO grade II glioma and may aid in glioma management.

Highlights

  • Large-scale tumor genomics research has altered the perspective of tumor research by revealing a novel method for classification of central nervous system (CNS) tumors, especially for the most malignant primary brain tumor: gliomas

  • The clinical characteristics of patients with mutations in pTERT were associated with poor prognosis with glioblastomas and a good prognosis with oligodendroglioma [6, 35, 36]

  • Based on the presence of pTERT mutations, IDH1/2 mutations, and 1p/19q codeletion status, gliomas were divided into five subtypes with different overall survival [37]

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Summary

Introduction

Large-scale tumor genomics research has altered the perspective of tumor research by revealing a novel method for classification of central nervous system (CNS) tumors, especially for the most malignant primary brain tumor: gliomas. Gliomas are primarily classified based on the molecular characteristics of tumor tissues according to the 2016 World Health Organization (WHO) classification of CNS tumors [1], with the status of these molecular biomarkers guiding the chemotherapy and radiation therapy strategies after surgical resection. Based on these new classification standards, glioblastomas and oligodendrogliomas often exhibit mutations in the telomerase reverse transcriptase promoter (pTERT) [1, 2]. Mutations in pTERT in IDH-wild-type diffuse gliomas and glioblastomas suggest a poor prognosis [6]. Determining pTERT status can be helpful for predicting prognosis and optimizing clinical treatment targets

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