Daily Papers

Laboratory test results are an important and generally high dimensional component of a patient's Electronic Health Record (EHR). We train embedding representations (via Word2Vec and GloVe) for LOINC codes of laboratory tests from the EHRs of about 80,000 patients at a cancer center. To include information about lab test outcomes, we also train embeddings on the concatenation of a LOINC code with a symbol indicating normality or abnormality of the result. We observe several clinically meaningful similarities among LOINC embeddings trained over our data. For the embeddings of the concatenation of LOINCs with abnormality codes, we evaluate the performance for mortality prediction tasks and the ability to preserve ordinality properties: i.e. a lab test with normal outcome should be more similar to an abnormal one than to the a very abnormal one.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

Objective: The reading level of health educational materials significantly influences the understandability and accessibility of the information, particularly for minoritized populations. Many patient educational resources surpass the reading level and complexity of widely accepted standards. There is a critical need for high-performing text simplification models in health information to enhance dissemination and literacy. This need is particularly acute in cancer education, where effective prevention and screening education can substantially reduce morbidity and mortality. Methods: We introduce Simplified Digestive Cancer (SimpleDC), a parallel corpus of cancer education materials tailored for health text simplification research, comprising educational content from the American Cancer Society, Centers for Disease Control and Prevention, and National Cancer Institute. Utilizing SimpleDC alongside the existing Med-EASi corpus, we explore Large Language Model (LLM)-based simplification methods, including fine-tuning, reinforcement learning (RL), reinforcement learning with human feedback (RLHF), domain adaptation, and prompt-based approaches. Our experimentation encompasses Llama 2 and GPT-4. A novel RLHF reward function is introduced, featuring a lightweight model adept at distinguishing between original and simplified texts, thereby enhancing the model's effectiveness with unlabeled data. Results: Fine-tuned Llama 2 models demonstrated high performance across various metrics. Our innovative RLHF reward function surpassed existing RL text simplification reward functions in effectiveness. The results underscore that RL/RLHF can augment fine-tuning, facilitating model training on unlabeled text and improving performance.

Detecting breast cancer early is of the utmost importance to effectively treat the millions of women afflicted by breast cancer worldwide every year. Although mammography is the primary imaging modality for screening breast cancer, there is an increasing interest in adding magnetic resonance imaging (MRI) to screening programmes, particularly for women at high risk. Recent guidelines by the European Society of Breast Imaging (EUSOBI) recommended breast MRI as a supplemental screening tool for women with dense breast tissue. However, acquiring and reading MRI scans requires significantly more time from expert radiologists. This highlights the need to develop new automated methods to detect cancer accurately using MRI and Artificial Intelligence (AI), which have the potential to support radiologists in breast MRI interpretation and classification and help detect cancer earlier. For this reason, the ODELIA consortium has made this multi-centre dataset publicly available to assist in developing AI tools for the detection of breast cancer on MRI.

Breast cancer is a major cause of cancer death among women, emphasising the importance of early detection for improved treatment outcomes and quality of life. Mammography, the primary diagnostic imaging test, poses challenges due to the high variability and patterns in mammograms. Double reading of mammograms is recommended in many screening programs to improve diagnostic accuracy but increases radiologists' workload. Researchers explore Machine Learning models to support expert decision-making. Stand-alone models have shown comparable or superior performance to radiologists, but some studies note decreased sensitivity with multiple datasets, indicating the need for high generalisation and robustness models. This work devises MammoDG, a novel deep-learning framework for generalisable and reliable analysis of cross-domain multi-center mammography data. MammoDG leverages multi-view mammograms and a novel contrastive mechanism to enhance generalisation capabilities. Extensive validation demonstrates MammoDG's superiority, highlighting the critical importance of domain generalisation for trustworthy mammography analysis in imaging protocol variations.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

In breast cancer imaging, there has been a trend to directly predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) from histological images based on deep learning (DL). However, it has been a commonly known problem that the constructed DL-based models numerically have better performances in internal validation than in external validation. The primary reason for this situation lies in that the distribution of the external data for validation is different from the distribution of the training data for the construction of the predictive model. In this paper, we aim to alleviate this situation with a more intrinsic approach. We propose an experts' cognition-driven ensemble deep learning (ECDEDL) approach for external validation of predicting pCR to NAC from histological images in breast cancer. The proposed ECDEDL, which takes the cognition of both pathology and artificial intelligence experts into consideration to improve the generalization of the predictive model to the external validation, more intrinsically approximates the working paradigm of a human being which will refer to his various working experiences to make decisions. The proposed ECDEDL approach was validated with 695 WSIs collected from the same center as the primary dataset to develop the predictive model and perform the internal validation, and 340 WSIs collected from other three centers as the external dataset to perform the external validation. In external validation, the proposed ECDEDL approach improves the AUCs of pCR prediction from 61.52(59.80-63.26) to 67.75(66.74-68.80) and the Accuracies of pCR prediction from 56.09(49.39-62.79) to 71.01(69.44-72.58). The proposed ECDEDL was quite effective for external validation, numerically more approximating the internal validation.

Motivation: The Genomic Data Commons (GDC) provides access to high quality, harmonized cancer genomics data through a unified curation and analysis platform centered around patient cohorts. While GDC users can interactively create complex cohorts through the graphical Cohort Builder, users (especially new ones) may struggle to find specific cohort descriptors across hundreds of possible fields and properties. However, users may be better able to describe their desired cohort in free-text natural language. Results: We introduce GDC Cohort Copilot, an open-source copilot tool for curating cohorts from the GDC. GDC Cohort Copilot automatically generates the GDC cohort filter corresponding to a user-input natural language description of their desired cohort, before exporting the cohort back to the GDC for further analysis. An interactive user interface allows users to further refine the generated cohort. We develop and evaluate multiple large language models (LLMs) for GDC Cohort Copilot and demonstrate that our locally-served, open-source GDC Cohort LLM achieves better results than GPT-4o prompting in generating GDC cohorts. Availability and implementation: The standalone docker image for GDC Cohort Copilot is available at https://quay.io/repository/cdis/gdc-cohort-copilot. Source code is available at https://github.com/uc-cdis/gdc-cohort-copilot. GDC Cohort LLM weights are available at https://huggingface.co/uc-ctds.

Cancer is a complex disease, the understanding and treatment of which are being aided through increases in the volume of collected data and in the scale of deployed computing power. Consequently, there is a growing need for the development of data-driven and, in particular, deep learning methods for various tasks such as cancer diagnosis, detection, prognosis, and prediction. Despite recent successes, however, designing high-performing deep learning models for nonimage and nontext cancer data is a time-consuming, trial-and-error, manual task that requires both cancer domain and deep learning expertise. To that end, we develop a reinforcement-learning-based neural architecture search to automate deep-learning-based predictive model development for a class of representative cancer data. We develop custom building blocks that allow domain experts to incorporate the cancer-data-specific characteristics. We show that our approach discovers deep neural network architectures that have significantly fewer trainable parameters, shorter training time, and accuracy similar to or higher than those of manually designed architectures. We study and demonstrate the scalability of our approach on up to 1,024 Intel Knights Landing nodes of the Theta supercomputer at the Argonne Leadership Computing Facility.