Concordance-based Predictive Uncertainty (CPU)-Index: Proof-of-concept with application towards improved specificity of lung cancers on low dose screening CT.

In this paper, we introduce a novel concordance-based predictive uncertainty (CPU)-Index, which integrates insights from subgroup analysis and personalized AI time-to-event models. Through its application in refining lung cancer screening (LCS) predictions generated by an individualized AI time-to-event model trained with fused data of low dose CT (LDCT) radiomics with patient demographics, we demonstrate its effectiveness, resulting in improved risk assessment compared to the Lung CT Screening Reporting & Data System (Lung-RADS). Subgroup-based Lung-RADS faces challenges in representing individual variations and relies on a limited set of predefined characteristics, resulting in variable predictions. Conversely, personalized AI time-to-event models are hindered by transparency issues and biases from censored data. By measuring the prediction consistency between subgroup analysis and AI time-to-event models, the CPU-Index framework offers a nuanced evaluation of the bias-variance trade-off and improves the transparency and reliability of predictions. Consistency was estimated by the concordance index of subgroup analysis-based similarity rank and model prediction similarity rank. Subgroup analysis-based similarity loss was defined as the sum-of-the-difference between Lung-RADS and feature-level 0-1 loss. Model prediction similarity loss was defined as squared loss. To test our approach, we identified 3,326 patients who underwent LDCT for LCS from 1/1/2015 to 6/30/2020 with confirmation of lung cancer on pathology within one year. For each LDCT image, the lesion associated with a Lung-RADS score was detected using a pretrained deep learning model from Medical Open Network for AI (MONAI), from which radiomic features were extracted. Radiomics were optimally fused with patient demographics via a positional encoding scheme and used to train a neural multi-task logistic regression time-to-event model that predicts malignancy. Performance was maximized when radiomics features were fused with positionally encoded demographic features. In this configuration, our algorithm raised the AUC from 0.81 ± 0.04 to 0.89 ± 0.02. Compared to standard Lung-RADS, our approach reduced the False-Positive-Rate from 0.41 ± 0.02 to 0.30 ± 0.12 while maintaining the same False-Negative-Rate. Our methodology enhances lung cancer risk assessment by estimating prediction uncertainty and adjusting accordingly. Furthermore, the optimal integration of radiomics and patient demographics improved overall diagnostic performance, indicating their complementary nature.