Abstract Background Brain metastasis invasion pattern (BMIP) is an emerging biomarker associated with recurrence-free and overall survival in patients, and differential response to therapy in preclinical models. Currently, BMIP can only be determined from the histopathological examination of surgical specimens, precluding its use as a biomarker prior to therapy initiation. The aim of this study was to investigate the potential of machine learning (ML) approaches to develop a non-invasive magnetic resonance imaging (MRI)-based biomarker for BMIP determination. Methods From an initial cohort of 329 patients, a subset of 132 patients met inclusion criteria for this retrospective study. We evaluated the ability of an expert neuroradiologist to reliably predict BMIP. Thereafter, the dataset was randomly divided into training/validation (80% of cases) and test subsets (20% of cases). Ground truth for BMIP was histopathologic evaluation of resected specimens. Following MRI sequence co-registration, advanced feature extraction techniques deriving hand-crafted radiomic features with traditional ML classifiers and convolution-based deep learning (CDL) models were trained and evaluated. Different ML approaches were used individually or using ensembling techniques to determine the model with the best performance for BMIP prediction. Results Expert evaluation of brain MRI scans could not reliably predict BMIP, with an accuracy of 44-59% depending on the semantic feature used. Among the different ML and CDL models evaluated, the best performing model achieved an accuracy of 85% and an F1-score of 90%. Conclusion ML approaches can effectively predict BMIP, representing a non-invasive MRI-based approach to guide management of patients with brain metastases.
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