Pathology image-based lung cancer subtyping using deep-learning features and cell-density maps

Abstract

In this paper, we propose a patch-based system to classify non-small cell lung cancer (NSCLC) diagnostic whole slide images (WSIs) into two major histopathological subtypes: adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Classifying patients accurately is important for prognosis and therapy decisions. The proposed system was trained and tested on 876 subtyped NSCLC gigapixel-resolution diagnostic WSIs from 805 patients – 664 in the training set and 141 in the test set. The algorithm has modules for: 1) auto-generated tumor/non-tumor masking using a trained residual neural network (ResNet34), 2) cell-density map generation (based on color deconvolution, local drain segmentation, and watershed transformation), 3) patch-level feature extraction using a pre-trained ResNet34, 4) a tower of linear SVMs for different cell ranges, and 5) a majority voting module for aggregating subtype predictions in unseen testing WSIs. The proposed system was trained and tested on several WSI magnifications ranging from x4 to x40 with a best ROC AUC of 0.95 and an accuracy of 0.86 in test samples. This fully-automated histopathology subtyping method outperforms similar published state-of-the-art methods for diagnostic WSIs.