Abstract 2096: A deep learning system to predict disease-specific survival in stage II and stage III colorectal cancer
Authors: Wulczyn Ellery , Steiner David F. , Moran Melissa , Plass Markus , Reihs Robert , Mueller Heimo , Sadhwani Apaar , Cai Yuannan , Flament Isabelle , Chen Po-Hsuan Cameron , Liu Yun , Stumpe Martin C. , Xu Zhaoyang , Zatloukal Kurt , Mermel Craig H. 
Published: September 2020

Abstract
Accurate prognosis in colorectal cancer can have important implications for clinical management. Here, we develop a deep learning system (DLS) to first identify invasive cancer and then directly predict disease specific survival (DSS) for stage II and stage III colorectal cancer using only digitized histopathology whole-slide images. The DLS was trained using slides from 1173 stage II and 1266 stage III cases (18,304 total slides) and was evaluated on a held-out test set of 601 stage II and 638 stage III cases (9,340 total slides). The area under the receiver operating characteristic curve (AUC) for 5-year DSS prediction was 68.0 for stage II (95% CI 62.2-73.1) and 65.5 for stage III (95% CI 61.1-70.0). For stage II, 5-year DSS was 64% for DLS-predicted high-risk cases versus 89% for DLS-predicted low-risk cases (upper and lower risk quartiles; p&lt;0.001, log rank test). For stage III, 5-year DSS was 35% for DLS-predicted high-risk cases versus 66% for DLS-predicted low-risk cases (upper and lower risk quartiles; p&lt;0.001, log rank test). In a multivariable Cox model, the DLS prediction remained significantly associated with DSS after adjusting for T-category, N-category, age, gender, tumor grade, and lymphovascular invasion (stage II: adjusted hazard ratio 1.55, 95% CI 1.33-1.81, p&lt;0.0001; stage III: adjusted hazard ratio 1.35, 95% CI (1.21-1.51), p&lt;0.0001). Finally, a combined proportional-hazards model using the DLS along with baseline clinicopathologic information provided better risk prediction than the DLS or baseline information alone, increasing 5-year AUC over the baseline-only model by 8.9 points (95% CI 3.9-13.6) and 5.3 points (95% CI 2.3-8.4) for stages II and III, respectively. Taken together, these findings demonstrate that the DLS provides significant prognostic value and risk stratification in both stage II and stage III colorectal cancer, and can be combined with known risk features to further improve prognostic accuracy. This represents novel work to train a DLS to directly predict patient outcomes using whole-slide images and weakly supervised learning. The ability to use non-annotated slides as input has important implications for possible clinical applications and the features learned by the model may also help to identify new prognosis-associated morphologic factors in colorectal cancer. Additional work is ongoing to confirm the utility of these findings, such as validation in additional datasets and interpretability experiments to better understand the features learned by the DLS for these predictions.
Citation Format: Ellery Wulczyn, David F. Steiner, Melissa Moran, Markus Plass, Robert Reihs, Heimo Mueller, Apaar Sadhwani, Yuannan Cai, Isabelle Flament, Po-Hsuan Cameron Chen, Yun Liu, Martin C. Stumpe, Zhaoyang Xu, Kurt Zatloukal, Craig H. Mermel. A deep learning system to predict disease-specific survival in stage II and stage III colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2096.