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Prediction of overall survival and molecular markers in gliomas via analysis of digital pathology images using deep learning

Cancer histology reveals disease progression and associated molecular processes, and contains rich phenotypic information that is predictive of outcome. In this paper, we developed a computational approach based on deep learning to predict the overall survival and molecular subtypes of glioma patients from microscopic images of tissue biopsies, reflecting measures of microvascular proliferation, mitotic activity, nuclear atypia, and the presence of necrosis. Whole-slide images from 663 unique patients [IDH: 333 IDH-wildtype, 330 IDH-mutants, 1p/19q: 201 1p/19q non-codeleted, 129 1p/19q codeleted] were obtained from TCGA. Sub-images that were free of artifacts and that contained viable tumor with descriptive histologic characteristics were extracted, which were further used for training and testing a deep neural network. The output layer of the network was configured in two different ways: (i) a final Cox model layer to output a prediction of patient risk, and (ii) a final layer with sigmoid activation function, and stochastic gradient decent based optimization with binary cross-entropy loss. Both survival prediction and molecular subtype classification produced promising results using our model. The c-statistic was estimated to be 0.82 (p-value=4.8x10-5) between the risk scores of the proposed deep learning model and overall survival, while accuracies of 88% (area under the curve [AUC]=0.86) were achieved in the detection of IDH mutational status and 1p/19q codeletion. These findings suggest that the deep learning techniques can be applied to microscopic images for objective, accurate, and integrated prediction of outcome for glioma patients. The proposed marker may contribute to (i) stratification of patients into clinical trials, (ii) patient selection for targeted therapy, and (iii) personalized treatment planning.

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