Dataset Information

A deep learning-based framework for lung cancer survival analysis with biomarker interpretation.

ABSTRACT: BACKGROUND:Lung cancer is the leading cause of cancer-related deaths in both men and women in the United States, and it has a much lower five-year survival rate than many other cancers. Accurate survival analysis is urgently needed for better disease diagnosis and treatment management. RESULTS:In this work, we propose a survival analysis system that takes advantage of recently emerging deep learning techniques. The proposed system consists of three major components. 1) The first component is an end-to-end cellular feature learning module using a deep neural network with global average pooling. The learned cellular representations encode high-level biologically relevant information without requiring individual cell segmentation, which is aggregated into patient-level feature vectors by using a locality-constrained linear coding (LLC)-based bag of words (BoW) encoding algorithm. 2) The second component is a Cox proportional hazards model with an elastic net penalty for robust feature selection and survival analysis. 3) The third commponent is a biomarker interpretation module that can help localize the image regions that contribute to the survival model's decision. Extensive experiments show that the proposed survival model has excellent predictive power for a public (i.e., The Cancer Genome Atlas) lung cancer dataset in terms of two commonly used metrics: log-rank test (p-value) of the Kaplan-Meier estimate and concordance index (c-index). CONCLUSIONS:In this work, we have proposed a segmentation-free survival analysis system that takes advantage of the recently emerging deep learning framework and well-studied survival analysis methods such as the Cox proportional hazards model. In addition, we provide an approach to visualize the discovered biomarkers, which can serve as concrete evidence supporting the survival model's decision.

SUBMITTER: Cui L

PROVIDER: S-EPMC7079513 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A deep learning-based framework for lung cancer survival analysis with biomarker interpretation.

Cui Lei L Li Hansheng H Hui Wenli W Chen Sitong S Yang Lin L Kang Yuxin Y Bo Qirong Q Feng Jun J

BMC bioinformatics 20200318 1

<h4>Background</h4>Lung cancer is the leading cause of cancer-related deaths in both men and women in the United States, and it has a much lower five-year survival rate than many other cancers. Accurate survival analysis is urgently needed for better disease diagnosis and treatment management.<h4>Results</h4>In this work, we propose a survival analysis system that takes advantage of recently emerging deep learning techniques. The proposed system consists of three major components. 1) The first c ...[more]

PMID: 32183709

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Project description:Digital pathology coupled with advanced machine learning (e.g., deep learning) has been changing the paradigm of whole-slide histopathological images (WSIs) analysis. Major applications in digital pathology using machine learning include automatic cancer classification, survival analysis, and subtyping from pathological images. While most pathological image analyses are based on patch-wise processing due to the extremely large size of histopathology images, there are several applications that predict a single clinical outcome or perform pathological diagnosis per slide (e.g., cancer classification, survival analysis). However, current slide-based analyses are task-dependent, and a general framework of slide-based analysis in WSI has been seldom investigated. We propose a novel slide-based histopathology analysis framework that creates a WSI representation map, called HipoMap, that can be applied to any slide-based problems, coupled with convolutional neural networks. HipoMap converts a WSI of various shapes and sizes to structured image-type representation. Our proposed HipoMap outperformed existing methods in intensive experiments with various settings and datasets. HipoMap showed the Area Under the Curve (AUC) of 0.96±0.026 (5% improved) in the experiments for lung cancer classification, and c-index of 0.787±0.013 (3.5% improved) and coefficient of determination ([Formula: see text]) of 0.978±0.032 (24% improved) in survival analysis and survival prediction with TCGA lung cancer data respectively, as a general framework of slide-based analysis with a flexible capability. The results showed significant improvement comparing to the current state-of-the-art methods on each task. We further discussed experimental results of HipoMap as pathological viewpoints and verified the performance using publicly available TCGA datasets. A Python package is available at https://pypi.org/project/hipomap , and the package can be easily installed using Python PIP. The open-source codes in Python are available at: https://github.com/datax-lab/HipoMap .

Project description:Breast cancer tumor grade is strongly associated with patient survival. In current clinical practice, pathologists assign tumor grade after visual analysis of tissue specimens. However, different studies show significant inter-observer variation in breast cancer grading. Computer-based breast cancer grading methods have been proposed but only work on specifically selected tissue areas and/or require labor-intensive annotations to be applied to new datasets. In this study, we trained and evaluated a deep learning-based breast cancer grading model that works on whole-slide histopathology images. The model was developed using whole-slide images from 706 young (< 40 years) invasive breast cancer patients with corresponding tumor grade (low/intermediate vs. high), and its constituents nuclear grade, tubule formation and mitotic rate. The performance of the model was evaluated using Cohen's kappa on an independent test set of 686 patients using annotations by expert pathologists as ground truth. The predicted low/intermediate (n = 327) and high (n = 359) grade groups were used to perform survival analysis. The deep learning system distinguished low/intermediate versus high tumor grade with a Cohen's Kappa of 0.59 (80% accuracy) compared to expert pathologists. In subsequent survival analysis the two groups predicted by the system were found to have a significantly different overall survival (OS) and disease/recurrence-free survival (DRFS/RFS) (p < 0.05). Univariate Cox hazard regression analysis showed statistically significant hazard ratios (p < 0.05). After adjusting for clinicopathologic features and stratifying for molecular subtype the hazard ratios showed a trend but lost statistical significance for all endpoints. In conclusion, we developed a deep learning-based model for automated grading of breast cancer on whole-slide images. The model distinguishes between low/intermediate and high grade tumors and finds a trend in the survival of the two predicted groups.

Dataset Information

A deep learning-based framework for lung cancer survival analysis with biomarker interpretation.

Publications

A deep learning-based framework for lung cancer survival analysis with biomarker interpretation.

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