RadioPathomics: Multimodal Learning in Non-Small Cell Lung Cancer for Adaptive Radiotherapy

The current cancer treatment practice collects multimodal data, such as radiology images, histopathology slides, genomics and clinical data. The importance of these data sources taken individually has fostered the recent raise of radiomics and pathomics, i.e. the extraction of quantitative features from radiology and histopathology images routinely collected to predict clinical outcomes or to guide clinical decisions using artificial intelligence algorithms. Nevertheless, how to combine them into a single multimodal framework is still an open issue. In this work we therefore develop a multimodal late fusion approach that combines hand-crafted features computed from radiomics, pathomics and clinical data to predict radiation therapy treatment outcomes for non-small-cell lung cancer patients. Within this context, we investigate eight different late fusion rules (i.e. product, maximum, minimum, mean, decision template, Dempster-Shafer, majority voting, and confidence rule) and two patient-wise aggregation rules leveraging the richness of information given by computer tomography images and whole-slide scans. The experiments in leave-one-patient-out cross-validation on an in-house cohort of 33 patients show that the proposed multimodal paradigm with an AUC equal to $90.9\%$ outperforms each unimodal approach, suggesting that data integration can advance precision medicine. As a further contribution, we also compare the hand-crafted representations with features automatically computed by deep networks, and the late fusion paradigm with early fusion, another popular multimodal approach. In both cases, the experiments show that the proposed multimodal approach provides the best results.