Dataset Information

Deep learning-based survival prediction for multiple cancer types using histopathology images.

ABSTRACT: Providing prognostic information at the time of cancer diagnosis has important implications for treatment and monitoring. Although cancer staging, histopathological assessment, molecular features, and clinical variables can provide useful prognostic insights, improving risk stratification remains an active research area. We developed a deep learning system (DLS) to predict disease specific survival across 10 cancer types from The Cancer Genome Atlas (TCGA). We used a weakly-supervised approach without pixel-level annotations, and tested three different survival loss functions. The DLS was developed using 9,086 slides from 3,664 cases and evaluated using 3,009 slides from 1,216 cases. In multivariable Cox regression analysis of the combined cohort including all 10 cancers, the DLS was significantly associated with disease specific survival (hazard ratio of 1.58, 95% CI 1.28-1.70, p<0.0001) after adjusting for cancer type, stage, age, and sex. In a per-cancer adjusted subanalysis, the DLS remained a significant predictor of survival in 5 of 10 cancer types. Compared to a baseline model including stage, age, and sex, the c-index of the model demonstrated an absolute 3.7% improvement (95% CI 1.0-6.5) in the combined cohort. Additionally, our models stratified patients within individual cancer stages, particularly stage II (p = 0.025) and stage III (p<0.001). By developing and evaluating prognostic models across multiple cancer types, this work represents one of the most comprehensive studies exploring the direct prediction of clinical outcomes using deep learning and histopathology images. Our analysis demonstrates the potential for this approach to provide significant prognostic information in multiple cancer types, and even within specific pathologic stages. However, given the relatively small number of cases and observed clinical events for a deep learning task of this type, we observed wide confidence intervals for model performance, thus highlighting that future work will benefit from larger datasets assembled for the purposes for survival modeling.

SUBMITTER: Wulczyn E

PROVIDER: S-EPMC7299324 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Deep learning-based survival prediction for multiple cancer types using histopathology images.

Wulczyn Ellery E Steiner David F DF Xu Zhaoyang Z Sadhwani Apaar A Wang Hongwu H Flament-Auvigne Isabelle I Mermel Craig H CH Chen Po-Hsuan Cameron PC Liu Yun Y Stumpe Martin C MC

PloS one 20200617 6

Providing prognostic information at the time of cancer diagnosis has important implications for treatment and monitoring. Although cancer staging, histopathological assessment, molecular features, and clinical variables can provide useful prognostic insights, improving risk stratification remains an active research area. We developed a deep learning system (DLS) to predict disease specific survival across 10 cancer types from The Cancer Genome Atlas (TCGA). We used a weakly-supervised approach w ...[more]

PMID: 32555646

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Project description:BackgroundOvarian cancer remains the leading gynecological cause of cancer mortality. Predicting the sensitivity of ovarian cancer to chemotherapy at the time of pathological diagnosis is a goal of precision medicine research that we have addressed in this study using a novel deep-learning neural network framework to analyze the histopathological images.MethodsWe have developed a method based on the Inception V3 deep learning algorithm that complements other methods for predicting response to standard platinum-based therapy of the disease. For the study, we used histopathological H&E images (pre-treatment) of high-grade serous carcinoma from The Cancer Genome Atlas (TCGA) Genomic Data Commons portal to train the Inception V3 convolutional neural network system to predict whether cancers had independently been labeled as sensitive or resistant to subsequent platinum-based chemotherapy. The trained model was then tested using data from patients left out of the training process. We used receiver operating characteristic (ROC) and confusion matrix analyses to evaluate model performance and Kaplan-Meier survival analysis to correlate the predicted probability of resistance with patient outcome. Finally, occlusion sensitivity analysis was piloted as a start toward correlating histopathological features with a response.ResultsThe study dataset consisted of 248 patients with stage 2 to 4 serous ovarian cancer. For a held-out test set of forty patients, the trained deep learning network model distinguished sensitive from resistant cancers with an area under the curve (AUC) of 0.846 ± 0.009 (SE). The probability of resistance calculated from the deep-learning network was also significantly correlated with patient survival and progression-free survival. In confusion matrix analysis, the network classifier achieved an overall predictive accuracy of 85% with a sensitivity of 73% and specificity of 90% for this cohort based on the Youden-J cut-off. Stage, grade, and patient age were not statistically significant for this cohort size. Occlusion sensitivity analysis suggested histopathological features learned by the network that may be associated with sensitivity or resistance to the chemotherapy, but multiple marker studies will be necessary to follow up on those preliminary results.ConclusionsThis type of analysis has the potential, if further developed, to improve the prediction of response to therapy of high-grade serous ovarian cancer and perhaps be useful as a factor in deciding between platinum-based and other therapies. More broadly, it may increase our understanding of the histopathological variables that predict response and may be adaptable to other cancer types and imaging modalities.

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Dataset Information

Deep learning-based survival prediction for multiple cancer types using histopathology images.

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Deep learning-based survival prediction for multiple cancer types using histopathology images.

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