Radiomics-Based Prediction of TERT Promotor Mutations in Intracranial High-Grade Meningiomas

Author:

Akkurt Burak Han1ORCID,Spille Dorothee Cäcilia2ORCID,Peetz-Dienhart Susanne3,Kiolbassa Nora Maren2,Mawrin Christian4,Musigmann Manfred1,Heindel Walter Leonhard1,Paulus Werner3,Stummer Walter2,Mannil Manoj15,Brokinkel Benjamin23

Affiliation:

1. Department of Radiology, University Hospital Muenster, DE-48149 Muenster, Germany

2. Department of Neurosurgery, University Hospital Muenster, DE-48149 Muenster, Germany

3. Institute of Neuropathology, University Hospital Muenster, DE-48149 Muenster, Germany

4. Department of Neuropathology, University Hospital Magdeburg, 39120 Magdeburg, Germany

5. Institute for Diagnostic and Interventional Radiology, Caritas-Hospital, DE-97980 Bad Mergentheim, Germany

Abstract

Purpose: In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk for promotor mutations could enable more targeted molecular analyses and improve diagnosis and treatment. Methods: Semiautomatic segmentation of intracranial grade 2/3 meningiomas was performed on preoperative magnetic resonance imaging. Discriminatory power to predict TERT promoter mutations was analyzed using a random forest algorithm with an increasing number of radiomic features. Two final models with five and eight features with both fixed and differing radiomics features were developed and adjusted to eliminate random effects and to avoid overfitting. Results: A total of 117 image sets including training (N = 94) and test data (N = 23) were analyzed. To eliminate random effects and demonstrate the robustness of our approach, data partitioning and subsequent model development and testing were repeated a total of 100 times (each time with repartitioned training and independent test data). The established five- and eight-feature models with both fixed and different radiomics features enabled the prediction of TERT with similar but excellent performance. The five-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 91.8%/94.3%, mean accuracy of 85.5%/88.9%, mean sensitivity of 88.6%/91.4%, mean specificity of 83.2%/87.0%, and a mean Cohen’s Kappa of 71.0%/77.7%. The eight-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 92.7%/94.6%, mean accuracy of 87.3%/88.9%, mean sensitivity of 89.6%/90.6%, mean specificity of 85.5%/87.5%, and a mean Cohen’s Kappa of 74.4%/77.6%. Of note, the addition of further features of up to N = 8 only slightly increased the performance. Conclusions: Radiomics-based machine learning enables prediction of TERT promotor mutation status in meningiomas with excellent discriminatory performance. Future analyses in larger cohorts should include grade 1 lesions as well as additional molecular alterations.

Funder

University of Muenster

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference34 articles.

1. Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system;Koelsche;Acta Neuropathol.,2013

2. Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: An individual patient data meta-analysis;Mirian;J. Neurol. Neurosurg. Psychiatry,2020

3. TERT Promoter Mutations and Risk of Recurrence in Meningioma;Sahm;J. Natl. Cancer Inst.,2016

4. Sahm, F., Brastianos, P.K., Claus, E.B., Mawrin, C., Perry, A., Santagata, S., von Deimlig, A., Brat, D.J., and Ellison, D.W. (2021). Central Nervous System Tumours, International Agency for Research on Cancer. [5th ed.].

5. Precision Digital Oncology: Emerging Role of Radiomics-based Biomarkers and Artificial Intelligence for Advanced Imaging and Characterization of Brain Tumors;Forghani;Radiol. Imaging Cancer,2020

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