Deep Learning-based Prediction of Breast Cancer Tumor and Immune Phenotypes from Histopathology

The interactions between tumor cells and the tumor microenvironment (TME) dictate therapeutic efficacy of radiation and many systemic therapies in breast cancer. However, to date, there is not a widely available method to reproducibly measure tumor and immune phenotypes for each patient's tumor. Given this unmet clinical need, we applied multiple instance learning (MIL) algorithms to assess activity of ten biologically relevant pathways from the hematoxylin and eosin (H&E) slide of primary breast tumors. We employed different feature extraction approaches and state-of-the-art model architectures. Using binary classification, our models attained area under the receiver operating characteristic (AUROC) scores above 0.70 for nearly all gene expression pathways and on some cases, exceeded 0.80. Attention maps suggest that our trained models recognize biologically relevant spatial patterns of cell sub-populations from H&E. These efforts represent a first step towards developing computational H&E biomarkers that reflect facets of the TME and hold promise for augmenting precision oncology.

Patient-specific, mechanistic models of tumor growth incorporating artificial intelligence and big data

Despite the remarkable advances in cancer diagnosis, treatment, and management that have occurred over the past decade, malignant tumors remain a major public health problem. Further progress in combating cancer may be enabled by personalizing the delivery of therapies according to the predicted response for each individual patient. The design of personalized therapies requires patient-specific information integrated into an appropriate mathematical model of tumor response. A fundamental barrier to realizing this paradigm is the current lack of a rigorous, yet practical, mathematical theory of tumor initiation, development, invasion, and response to therapy. In this review, we begin by providing an overview of different approaches to modeling tumor growth and treatment, including mechanistic as well as data-driven models based on ``big data" and artificial intelligence. Next, we present illustrative examples of mathematical models manifesting their utility and discussing the limitations of stand-alone mechanistic and data-driven models. We further discuss the potential of mechanistic models for not only predicting, but also optimizing response to therapy on a patient-specific basis. We then discuss current efforts and future possibilities to integrate mechanistic and data-driven models. We conclude by proposing five fundamental challenges that must be addressed to fully realize personalized care for cancer patients driven by computational models.

Estimating Test Performance for AI Medical Devices under Distribution Shift with Conformal Prediction

Estimating the test performance of software AI-based medical devices under distribution shifts is crucial for evaluating the safety, efficiency, and usability prior to clinical deployment. Due to the nature of regulated medical device software and the difficulty in acquiring large amounts of labeled medical datasets, we consider the task of predicting the test accuracy of an arbitrary black-box model on an unlabeled target domain without modification to the original training process or any distributional assumptions of the original source data (i.e. we treat the model as a "black-box" and only use the predicted output responses). We propose a "black-box" test estimation technique based on conformal prediction and evaluate it against other methods on three medical imaging datasets (mammography, dermatology, and histopathology) under several clinically relevant types of distribution shift (institution, hardware scanner, atlas, hospital). We hope that by promoting practical and effective estimation techniques for black-box models, manufacturers of medical devices will develop more standardized and realistic evaluation procedures to improve the robustness and trustworthiness of clinical AI tools.