Abstract Deep learning models have demonstrated the remarkable ability to infer cancer patient prognosis from molecular and anatomic pathology information. Studies in recent years have demonstrated that leveraging information from complementary multimodal data can improve prognostication, further illustrating the potential utility of such methods. Model interpretation is crucial for facilitating the clinical adoption of deep learning methods by fostering practitioner understanding and trust in the technology. However, while prior works have presented novel multimodal neural network architectures as means to improve prognostication performance, these approaches: 1) do not comprehensively leverage biological and histomorphological relationships and 2) make use of emerging strategies to “pretrain” models (i.e., train models on a slightly orthogonal dataset/modeling objective) which may aid prognostication by reducing the amount of information required for achieving optimal performance. Here, we develop an interpretable multimodal modeling framework that combines DNA methylation, gene expression, and histopathology (i.e., tissue slides) data, and we compare the performances of crossmodal pretraining, contrastive learning, and transfer learning versus the standard procedure in this context. Our models outperform the existing state-of-the-art method (average 11.54% C-index increase), and baseline clinically driven models. Our results demonstrate that the selection of pretraining strategies is crucial for obtaining highly accurate prognostication models, even more so than devising an innovative model architecture, and further emphasize the all-important role of the tumor microenvironment on disease progression.

Assessment of Emerging Pretraining Strategies in Interpretable Multimodal Deep Learning for Cancer Prognostication