Vanja Miskovic

Michele Zanitti, Vanja Miskovic, Francesco Trovò et al.

Predicting survival outcomes for non-small cell lung cancer (NSCLC) patients is challenging due to the different individual prognostic features. This task can benefit from the integration of whole-slide images, bulk transcriptomics, and DNA methylation, which offer complementary views of the patient's condition at diagnosis. However, real-world clinical datasets are often incomplete, with entire modalities missing for a significant fraction of patients. State-of-the-art models rely on available data to create patient-level representations or use generative models to infer missing modalities, but they lack robustness in cases of severe missingness. We propose a Multimodal Contrastive Variational AutoEncoder (MCVAE) to address this issue: modality-specific variational encoders capture the uncertainty in each data source, and a fusion bottleneck with learned gating mechanisms is introduced to normalize the contributions from present modalities. We propose a multi-task objective that combines survival loss and reconstruction loss to regularize patient representations, along with a cross-modal contrastive loss that enforces cross-modal alignment in the latent space. During training, we apply stochastic modality masking to improve the robustness to arbitrary missingness patterns. Extensive evaluations on the TCGA-LUAD (n=475) and TCGA-LUSC (n=446) datasets demonstrate the efficacy of our approach in predicting disease-specific survival (DSS) and its robustness to severe missingness scenarios compared to two state-of-the-art models. Finally, we bring some clarifications on multimodal integration by testing our model on all subsets of modalities, finding that integration is not always beneficial to the task.

Katinka Becker, Maximilian P. Oppelt, Tobias S. Zech et al.

Machine learning (ML) in medicine has transitioned from research to concrete applications aimed at supporting several medical purposes like therapy selection, monitoring and treatment. Acceptance and effective adoption by clinicians and patients, as well as regulatory approval, require evidence of trustworthiness. A major factor for the development of trustworthy AI is the quantification of data quality for AI model training and testing. We have recently proposed the METRIC-framework for systematically evaluating the suitability (fit-for-purpose) of data for medical ML for a given task. Here, we operationalize this theoretical framework by introducing a collection of data quality metrics - the metric library - for practically measuring data quality dimensions. For each metric, we provide a metric card with the most important information, including definition, applicability, examples, pitfalls and recommendations, to support the understanding and implementation of these metrics. Furthermore, we discuss strategies and provide decision trees for choosing an appropriate set of data quality metrics from the metric library given specific use cases. We demonstrate the impact of our approach exemplarily on the PTB-XL ECG-dataset. This is a first step to enable fit-for-purpose evaluation of training and test data in practice as the base for establishing trustworthy AI in medicine.

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.