Endometrial cancer (EC) is the most common gynecologic malignancy in the United States. Hormone therapies and hysterectomy are viable treatments for early-stage EC and atypical endometrial hyperplasia (AEH), a high-risk precursor to EC. Prediction of patient response to hormonal treatment is useful for patients to make treatment decisions. We have previously developed a mix-supervised model: a weakly supervised deep learning model for hormonal treatment response prediction based on pathologist-annotated AEH and EC regions on whole slide images of H&E stained slides. The reliance on pathologist annotation in applying the model to new cases is cumbersome and subject to inter-observer variability. In this study, we automate the task of ROI detection by developing a supervised deep learning model to detect AEH and EC regions. This model achieved a patch-wise AUROC performance of 0.974 (approximate 95% CI [0.972, 0.976]). The mixsupervised model yielded a patient-level AUROC of 0.76 (95% CI [0.59, 0.92]) with ROIs detected by our new model on a hold-out test set in the task of classifying patients into responders and non-responders. As a comparison, the original model as tested on pathologist-annotated ROIs achieved an AUROC of 0.80 with 95% CI [0.63, 0.95]. Our results demonstrate the potential of using weakly supervised deep learning and supervised ROI detection model for predicting hormonal treatment response in endometrial cancer patients.
PurposeEndometrial cancer (EC) is the most common gynecologic malignancy in the United States, and atypical endometrial hyperplasia (AEH) is considered a high-risk precursor to EC. Hormone therapies and hysterectomy are practical treatment options for AEH and early-stage EC. Some patients prefer hormone therapies for reasons such as fertility preservation or being poor surgical candidates. However, accurate prediction of an individual patient’s response to hormonal treatment would allow for personalized and potentially improved recommendations for these conditions. This study aims to explore the feasibility of using deep learning models on whole slide images (WSI) of endometrial tissue samples to predict the patient’s response to hormonal treatment.ApproachWe curated a clinical WSI dataset of 112 patients from two clinical sites. An expert pathologist annotated these images by outlining AEH/EC regions. We developed an end-to-end machine learning model with mixed supervision. The model is based on image patches extracted from pathologist-annotated AEH/EC regions. Either an unsupervised deep learning architecture (Autoencoder or ResNet50), or non-deep learning (radiomics feature extraction) is used to embed the images into a low-dimensional space, followed by fully connected layers for binary prediction, which was trained with binary responder/non-responder labels established by pathologists. We used stratified sampling to partition the dataset into a development set and a test set for internal validation of the performance of our models.ResultsThe autoencoder model yielded an AUROC of 0.80 with 95% CI [0.63, 0.95] on the independent test set for the task of predicting a patient with AEH/EC as a responder vs non-responder to hormonal treatment.ConclusionsThese findings demonstrate the potential of using mixed supervised machine learning models on WSIs for predicting the response to hormonal treatment in AEH/EC patients.
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