Predicting melanoma survival and metastasis with interpretable histopathological features and machine learning models.

Introduction: Melanoma is the fifth most common cancer in US, and the incidence is increasing 1.4% annually. The overall survival rate for early-stage disease is 99.4%. However, melanoma can recur years later (in the same region of the body or as distant metastasis), and results in a dramatically lower survival rate. Currently there is no reliable method to predict tumor recurrence and metastasis on early primary tumor histological images. Methods: To identify rapid, accurate, and cost-effective predictors of metastasis and survival, in this work, we applied various interpretable machine learning approaches to analyze melanoma histopathological H&E images. The result is a set of image features that can help clinicians identify high-risk-of-metastasis patients for increased clinical follow-up and precision treatment. We use simple models (i.e., logarithmic classification and KNN) and "human-interpretable" measures of cell morphology and tissue architecture (e.g., cell size, staining intensity, and cell density) to predict the melanoma survival on public and local Stage I-III cohorts as well as the metastasis risk on a local cohort. Results: We use penalized survival regression to limit features available to downstream classifiers and investigate the utility of convolutional neural networks in isolating tumor regions to focus morphology extraction on only the tumor region. This approach allows us to predict survival and metastasis with a maximum F1 score of 0.72 and 0.73, respectively, and to visualize several high-risk cell morphologies. Discussion: This lays the foundation for future work, which will focus on using our interpretable pipeline to predict metastasis in Stage I & II melanoma.