Trustworthy learning with (un)sure annotation for lung nodule diagnosis with CT

Recent evolution in deep learning has proven its value for CT-based lung nodule classification. Most current techniques are intrinsically black-box systems, suffering from two generalizability issues in clinical practice. First, benign-malignant discrimination is often assessed by human observers without pathologic diagnoses at the nodule level. We termed these data as "unsure-annotation data". Second, a classifier does not necessarily acquire reliable nodule features for stable learning and robust prediction with patch-level labels during learning. In this study, we construct a sure-annotation dataset with pathologically-confirmed labels and propose a collaborative learning framework to facilitate sure nodule classification by integrating unsure-annotation data knowledge through nodule segmentation and malignancy score regression. A loss function is designed to learn reliable features by introducing interpretability constraints regulated with nodule segmentation maps. Furthermore, based on model inference results that reflect the understanding from both machine and experts, we explore a new nodule analysis method for similar historical nodule retrieval and interpretable diagnosis. Detailed experimental results demonstrate that our approach is beneficial for achieving improved performance coupled with trustworthy model reasoning for lung cancer prediction with limited data. Extensive cross-evaluation results further illustrate the effect of unsure-annotation data for deep-learning based methods in lung nodule classification.