Direct Image to Subtype Prediction for Brain Tumors using Deep Learning

Abstract Background Deep Learning (DL) can predict molecular alterations of solid tumors directly from routine histopathology slides. Since the 2021 update of the World Health Organization (WHO) diagnostic criteria, the classification of brain tumors integrates both histopathological and molecular information. We hypothesize that DL can predict molecular alterations as well as WHO subtyping of brain tumors from hematoxylin and eosin-stained histopathology slides. Methods We used weakly supervised DL and applied it to three large cohorts of brain tumor samples, comprising N=2,845 patients. Results We found that the key molecular alterations for subtyping, IDH and ATRX, as well as 1p19q co-deletion, were predictable from histology with an area under the receiver operating characteristic curve (AUROC) of 0.95, 0.90 and 0.80 in the training cohort respectively. These findings were upheld in external validation cohorts with AUROCs of 0.90, 0.79 and 0.87 for prediction of IDH, ATRX and 1p19q co-deletion respectively. Conclusions In the future, such DL-based implementations could ease diagnostic workflows, particularly for situations in which advanced molecular testing is not readily available.