Regularized bidimensional estimation of the hazard rate

In epidemiological or demographic studies, with variable age at onset, a typical quantity of interest is the incidence of a disease (for example the cancer incidence). In these studies, the individuals are usually highly heterogeneous in terms of dates of birth (the cohort) and with respect to the calendar time (the period) and appropriate estimation methods are needed. In this article a new estimation method is presented which extends classical age-period-cohort analysis by allowing interactions between age, period and cohort effects. We introduce a bidimensional regularized estimate of the hazard rate where a penalty is introduced on the likelihood of the model. This penalty can be designed either to smooth the hazard rate or to enforce consecutive values of the hazard to be equal, leading to a parsimonious representation of the hazard rate. In the latter case, we make use of an iterative penalized likelihood scheme to approximate the L 0 norm, which makes the computation tractable. The method is evaluated on simulated data and applied on breast cancer survival data from the SEER program.

Deep Learning with Multimodal Representation for Pancancer Prognosis Prediction

Estimating the future course of cancer is invaluable to physicians; however, current clinical methods fail to effectively use the vast amount of multimodal data that is available for cancer patients.To tackle this problem, we constructed a deep neural network based model to predict the survival of patients for 20 different cancer types using gene expressions, microRNA data, clinical data and histopathology whole slide images (WSIs). We developed an unsupervised encoder to compress these four data modalities into a single feature vector for each patient, handling missing data through a resilient, multimodal dropout method. Encoding methods were tailored to each data type - using deep highway networks to extract features from genomic and clinical data, and convolutional neural networks extract features from pathology images. We then used these feature encodings trained on pancancer data to predict pancancer and single cancer survival data, achieving a C-index of 0.784 overall.This work shows that it is possible to build a pancancer model for prognosis that also predicts prognosis in single cancer sites. Furthermore, our model handles multiple data modalities, efficiently analyzes WSIs, and summarizes patient details flexibly into an unsupervised, informative profile. We thus present a powerful automated tool to accurately determine prognosis, a key step towards personalized treatment for cancer patients.