PurposeThe BRCA1-associated protein 1 (BAP1) gene is of great interest because somatic (BAP1) mutations are the most common alteration associated with pleural mesothelioma (PM). Further, germline mutation of the BAP1 gene has been linked to the development of PM. This study aimed to explore the potential of radiomics on computed tomography scans to identify somatic BAP1 gene mutations and assess the feasibility of radiomics in future research in identifying germline mutations.ApproachA cohort of 149 patients with PM and known somatic BAP1 mutation status was collected, and a previously published deep learning model was used to first automatically segment the tumor, followed by radiologist modifications. Image preprocessing was performed, and texture features were extracted from the segmented tumor regions. The top features were selected and used to train 18 separate machine learning models using leave-one-out cross-validation (LOOCV). The performance of the models in distinguishing between BAP1-mutated (BAP1+) and BAP1 wild-type (BAP1−) tumors was evaluated using the receiver operating characteristic area under the curve (ROC AUC).ResultsA decision tree classifier achieved the highest overall AUC value of 0.69 (95% confidence interval: 0.60 and 0.77). The features selected most frequently through the LOOCV were all second-order (gray-level co-occurrence or gray-level size zone matrices) and were extracted from images with an applied transformation.ConclusionsThis proof-of-concept work demonstrated the potential of radiomics to differentiate among BAP1+/− in patients with PM. Future work will extend these methods to the assessment of germline BAP1 mutation status through image analysis for improved patient prognostication.
The linking of image analysis, in particular radiomics, with genetic profiles, known as “imaging genomics,” has been successfully applied to many diseases and anatomic regions. The application of imaging genomics in mesothelioma, however, remains limited. Pleural mesothelioma (PM) is a devastating cancer associated with asbestos exposure and has a poor prognosis. The BRCA1-associated protein 1 (BAP1 ) gene is of considerable interest because somatic BAP1 mutations are the most common alteration associated with PM. Further, germline mutation of the BAP1 gene has been linked to PM. This study aims to explore the potential of radiomics to identify somatic BAP1 mutations and assess the feasibility of radiomics in future research in identifying germline mutations. A cohort of 149 patients with PM and known somatic BAP1 mutation status was collected, and a previously published deep learning model was used to automatically segment tumor on three representative sections from each patient’s computed tomography scans. Preprocessing, including gray-level discretization and resampling, was performed, and intensity-based and 2D texture features were extracted from the segmented tumor regions. Synthetic Minority Over-sampling Technique (SMOTE) combined with Tomek links was employed to address data imbalance. The top features were selected and used to train 18 separate machine learning models. The performance of the models in distinguishing between BAP1 -mutated (BAP1+) versus BAP1 wild-type (BAP1 -) tumors were evaluated using area under the receiver operating characteristic curve (ROC AUC) as the figure of merit. This study achieved an AUC value of 0.69 (95% confidence interval: 0.60, 0.77) using a decision tree classifier. Overall, this novel, proof-of-concept work demonstrates the potential of radiomics in differentiating between BAP1+/- in patients with PM. Future work will extend these methods to the assessment of germline BAP1 mutation status through image analysis for improved patient prognostication.
Radiomics can be used to generate a large magnitude of quantitative features from medical images that can be applied to various predictive tasks and treatment decisions. To ensure the generalizability of such methods, radiomic features need to be robust to variations in patient positioning and segmentation of regions of interest. Feature robustness is often determined through test-retest imaging, whereby the agreement of feature values from images acquired over a brief time interval is quantified to measure robustness. However, the scarcity of test-retest data is a significant limitation of such approaches, and there is a lack of consensus for alternative methods to determine feature robustness with single scans. Hence, this study evaluates the effectiveness of assessing feature robustness using various metrics to quantify the agreement of feature values before and after image perturbation. 1002 features were extracted from thoracic computed tomography scans of patients with pleural mesothelioma before and after perturbations, including rotation, erosion, dilation, and contour randomization, and five distinct metrics were used to assess feature agreement. Feature robustness was highly variable as quantified by various combinations of perturbations and metrics of agreement. The greatest stability in subsequent steps of the predictive pipeline including feature selection and classification was achieved using the concordance and intraclass correlation coefficients with chained perturbations of image rotation, contour erosion or dilation, and contour randomization. These findings suggest that the choice of image perturbations and metrics of agreement have non-negligible consequences on feature robustness estimates and the success of downstream predictive tasks, warranting careful consideration in experimental design.
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