Interventional cancer clinical trials are generally too restrictive, and some patients are often excluded on the basis of comorbidity, past or concomitant treatments, or the fact that they are over a certain age. The efficacy and safety of new treatments for patients with these characteristics are, therefore, not defined. In this work, we built a model to automatically predict whether short clinical statements were considered inclusion or exclusion criteria. We used protocols from cancer clinical trials that were available in public registries from the last 18 years to train word-embeddings, and we constructed a dataset of 6M short free-texts labeled as eligible or not eligible. A text classifier was trained using deep neural networks, with pre-trained word-embeddings as inputs, to predict whether or not short free-text statements describing clinical information were considered eligible. We additionally analyzed the semantic reasoning of the word-embedding representations obtained and were able to identify equivalent treatments for a type of tumor analogous with the drugs used to treat other tumors. We show that representation learning using deep neural networks can be successfully leveraged to extract the medical knowledge from clinical trial protocols for potentially assisting practitioners when prescribing treatments.

The prediction of microsatellite instability (MSI) using deep learning (DL) techniques could have significant benefits, including reducing cost and increasing MSI testing of colorectal cancer (CRC) patients. Nonetheless, batch effects or systematic biases are not well characterized in digital histology models and lead to overoptimistic estimates of model performance. Methods to not only palliate but to directly abrogate biases are needed. We present a multiple bias rejecting DL system based on adversarial networks for the prediction of MSI in CRC from tissue microarrays (TMAs), trained and validated in 1788 patients from EPICOLON and HGUA. The system consists of an end-to-end image preprocessing module that tile samples at multiple magnifications and a tissue classification module linked to the bias-rejecting MSI predictor. We detected three biases associated with the learned representations of a baseline model: the project of origin of samples, the patient’s spot and the TMA glass where each spot was placed. The system was trained to directly avoid learning the batch effects of those variables. The learned features from the bias-ablated model achieved maximum discriminative power with respect to the task and minimal statistical mean dependence with the biases. The impact of different magnifications, types of tissues and the model performance at tile vs patient level is analyzed. The AUC at tile level, and including all three selected tissues (tumor epithelium, mucin and lymphocytic regions) and 4 magnifications, was 0.87 ± 0.03 and increased to 0.9 ± 0.03 at patient level. To the best of our knowledge, this is the first work that incorporates a multiple bias ablation technique at the DL architecture in digital pathology, and the first using TMAs for the MSI prediction task.

This paper describes BIMCV COVID-19+, a large dataset from the Valencian Region Medical ImageBank (BIMCV) containing chest X-ray images CXR (CR, DX) and computed tomography (CT) imaging of COVID-19+ patients along with their radiological findings and locations, pathologies, radiological reports (in Spanish), DICOM metadata, Polymerase chain reaction (PCR), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) diagnostic antibody tests. The findings have been mapped onto standard Unified Medical Language System (UMLS) terminology and cover a wide spectrum of thoracic entities, unlike the considerably more reduced number of entities annotated in previous datasets. Images are stored in high resolution and entities are localized with anatomical labels and stored in a Medical Imaging Data Structure (MIDS) format. In addition, 10 images were annotated by a team of radiologists to include semantic segmentation of radiological findings. This first iteration of the database includes 1,380 CX, 885 DX and 163 CT studies from 1,311 COVID-19+ patients. This is, to the best of our knowledge, the largest COVID-19+ dataset of images available in an open format. The dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/bimcv-covid19.