Anna-Katharina Meißner1, Robin Gutsche2,3, Norbert Galldiks2,4,5, Martin Kocher2,6, Stephanie T Jünger1, Marie-Lisa Eich7, Manuel Montesinos-Rongen8, Anna Brunn8, Martina Deckert5,8, Christina Wendl9, Wolfgang Dietmaier10, Roland Goldbrunner1,5, Maximilian I Ruge5,6, Cornelia Mauch5,11, Nils-Ole Schmidt12, Martin Proescholdt12, Stefan Grau1,5, Philipp Lohmann2,6. 1. Center for Neurosurgery, Department of General Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. 2. Institute of Neuroscience and Medicine (INM-3, -4), Research Center Juelich, Juelich, Germany. 3. RWTH Aachen University, Aachen, Germany. 4. Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. 5. Center for Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Cologne, Germany. 6. Center for Neurosurgery, Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. 7. Department of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. 8. Institute of Neuropathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. 9. Department of Radiology and Division of Neuroradiology, University Hospital Regensburg, Regensburg, Germany. 10. Institute of Pathology and Molecular Pathology Diagnostic Unit, University Hospital Regensburg, Regensburg, Germany. 11. Department of Dermatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. 12. Department of Neurosurgery, University Hospital Regensburg, Regensburg, Germany.
Abstract
BACKGROUND: The BRAF V600E mutation is present in approximately 50% of patients with melanoma brain metastases and an important prerequisite for response to targeted therapies, particularly BRAF inhibitors. As heterogeneity in terms of BRAF mutation status may occur in melanoma patients, a wild-type extracranial primary tumor does not necessarily rule out a targetable mutation in brain metastases using BRAF inhibitors. We evaluated the potential of MRI radiomics for a noninvasive prediction of the intracranial BRAF mutation status. METHODS: Fifty-nine patients with melanoma brain metastases from two university brain tumor centers (group 1, 45 patients; group 2, 14 patients) underwent tumor resection with subsequent genetic analysis of the intracranial BRAF mutation status. Preoperative contrast-enhanced MRI was manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses. RESULTS: Twenty-two of 45 patients (49%) in group 1, and 8 of 14 patients (57%) in group 2 had an intracranial BRAF V600E mutation. A linear support vector machine classifier using a six-parameter radiomics signature yielded an area under the ROC curve of 0.92 (sensitivity, 83%; specificity, 88%) in the test data. CONCLUSIONS: The developed radiomics classifier allows a noninvasive prediction of the intracranial BRAF V600E mutation status in patients with melanoma brain metastases with high diagnostic performance.
BACKGROUND: The BRAF V600E mutation is present in approximately 50% of patients with melanoma brain metastases and an important prerequisite for response to targeted therapies, particularly BRAF inhibitors. As heterogeneity in terms of BRAF mutation status may occur in melanoma patients, a wild-type extracranial primary tumor does not necessarily rule out a targetable mutation in brain metastases using BRAF inhibitors. We evaluated the potential of MRI radiomics for a noninvasive prediction of the intracranial BRAF mutation status. METHODS: Fifty-nine patients with melanoma brain metastases from two university brain tumor centers (group 1, 45 patients; group 2, 14 patients) underwent tumor resection with subsequent genetic analysis of the intracranial BRAF mutation status. Preoperative contrast-enhanced MRI was manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses. RESULTS: Twenty-two of 45 patients (49%) in group 1, and 8 of 14 patients (57%) in group 2 had an intracranial BRAF V600E mutation. A linear support vector machine classifier using a six-parameter radiomics signature yielded an area under the ROC curve of 0.92 (sensitivity, 83%; specificity, 88%) in the test data. CONCLUSIONS: The developed radiomics classifier allows a noninvasive prediction of the intracranial BRAF V600E mutation status in patients with melanoma brain metastases with high diagnostic performance.
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