Marina Chiara Garassino

James M Dolezal, Andrew Srisuwananukorn, Dmitry Karpeyev et al.

A model's ability to express its own predictive uncertainty is an essential attribute for maintaining clinical user confidence as computational biomarkers are deployed into real-world medical settings. In the domain of cancer digital histopathology, we describe a novel, clinically-oriented approach to uncertainty quantification (UQ) for whole-slide images, estimating uncertainty using dropout and calculating thresholds on training data to establish cutoffs for low- and high-confidence predictions. We train models to identify lung adenocarcinoma vs. squamous cell carcinoma and show that high-confidence predictions outperform predictions without UQ, in both cross-validation and testing on two large external datasets spanning multiple institutions. Our testing strategy closely approximates real-world application, with predictions generated on unsupervised, unannotated slides using predetermined thresholds. Furthermore, we show that UQ thresholding remains reliable in the setting of domain shift, with accurate high-confidence predictions of adenocarcinoma vs. squamous cell carcinoma for out-of-distribution, non-lung cancer cohorts.

James M. Dolezal, Rachelle Wolk, Hanna M. Hieromnimon et al.

Artificial intelligence methods including deep neural networks (DNN) can provide rapid molecular classification of tumors from routine histology with accuracy that matches or exceeds human pathologists. Discerning how neural networks make their predictions remains a significant challenge, but explainability tools help provide insights into what models have learned when corresponding histologic features are poorly defined. Here, we present a method for improving explainability of DNN models using synthetic histology generated by a conditional generative adversarial network (cGAN). We show that cGANs generate high-quality synthetic histology images that can be leveraged for explaining DNN models trained to classify molecularly-subtyped tumors, exposing histologic features associated with molecular state. Fine-tuning synthetic histology through class and layer blending illustrates nuanced morphologic differences between tumor subtypes. Finally, we demonstrate the use of synthetic histology for augmenting pathologist-in-training education, showing that these intuitive visualizations can reinforce and improve understanding of histologic manifestations of tumor biology.

Chiara Giangregorio, Cristina Maria Licciardello, Vanja Miskovic et al.

Early detection of non-small cell lung cancer (NSCLC) is critical for improving patient outcomes, and novel approaches are needed to facilitate early diagnosis. In this study, we explore the use of automatic cough analysis as a pre-screening tool for distinguishing between NSCLC patients and healthy controls. Cough audio recordings were prospectively acquired from a total of 227 subjects, divided into NSCLC patients and healthy controls. The recordings were analyzed using machine learning techniques, such as support vector machine (SVM) and XGBoost, as well as deep learning approaches, specifically convolutional neural networks (CNN) and transfer learning with VGG16. To enhance the interpretability of the machine learning model, we utilized Shapley Additive Explanations (SHAP). The fairness of the models across demographic groups was assessed by comparing the performance of the best model across different age groups (less than or equal to 58y and higher than 58y) and gender using the equalized odds difference on the test set. The results demonstrate that CNN achieves the best performance, with an accuracy of 0.83 on the test set. Nevertheless, SVM achieves slightly lower performances (accuracy of 0.76 in validation and 0.78 in the test set), making it suitable in contexts with low computational power. The use of SHAP for SVM interpretation further enhances model transparency, making it more trustworthy for clinical applications. Fairness analysis shows slightly higher disparity across age (0.15) than gender (0.09) on the test set. Therefore, to strengthen our findings' reliability, a larger, more diverse, and unbiased dataset is needed -- particularly including individuals at risk of NSCLC and those in early disease stages.