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Deep segmentation networks predict survival of non-small cell lung cancer.

ABSTRACT: Non-small-cell lung cancer (NSCLC) represents approximately 80-85% of lung cancer diagnoses and is the leading cause of cancer-related death worldwide. Recent studies indicate that image-based radiomics features from positron emission tomography/computed tomography (PET/CT) images have predictive power for NSCLC outcomes. To this end, easily calculated functional features such as the maximum and the mean of standard uptake value (SUV) and total lesion glycolysis (TLG) are most commonly used for NSCLC prognostication, but their prognostic value remains controversial. Meanwhile, convolutional neural networks (CNN) are rapidly emerging as a new method for cancer image analysis, with significantly enhanced predictive power compared to hand-crafted radiomics features. Here we show that CNNs trained to perform the tumor segmentation task, with no other information than physician contours, identify a rich set of survival-related image features with remarkable prognostic value. In a retrospective study on pre-treatment PET-CT images of 96 NSCLC patients before stereotactic-body radiotherapy (SBRT), we found that the CNN segmentation algorithm (U-Net) trained for tumor segmentation in PET and CT images, contained features having strong correlation with 2- and 5-year overall and disease-specific survivals. The U-Net algorithm has not seen any other clinical information (e.g. survival, age, smoking history, etc.) than the images and the corresponding tumor contours provided by physicians. In addition, we observed the same trend by validating the U-Net features against an extramural data set provided by Stanford Cancer Institute. Furthermore, through visualization of the U-Net, we also found convincing evidence that the regions of metastasis and recurrence appear to match with the regions where the U-Net features identified patterns that predicted higher likelihoods of death. We anticipate our findings will be a starting point for more sophisticated non-intrusive patient specific cancer prognosis determination. For example, the deep learned PET/CT features can not only predict survival but also visualize high-risk regions within or adjacent to the primary tumor and hence potentially impact therapeutic outcomes by optimal selection of therapeutic strategy or first-line therapy adjustment.

SUBMITTER: Baek S

PROVIDER: S-EPMC6872742 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Deep segmentation networks predict survival of non-small cell lung cancer.

Baek Stephen S Baek Stephen S He Yusen Y Allen Bryan G BG Buatti John M JM Smith Brian J BJ Tong Ling L Sun Zhiyu Z Wu Jia J Diehn Maximilian M Loo Billy W BW Plichta Kristin A KA Seyedin Steven N SN Gannon Maggie M Cabel Katherine R KR Kim Yusung Y Wu Xiaodong X

Scientific reports 20191121 1

Non-small-cell lung cancer (NSCLC) represents approximately 80-85% of lung cancer diagnoses and is the leading cause of cancer-related death worldwide. Recent studies indicate that image-based radiomics features from positron emission tomography/computed tomography (PET/CT) images have predictive power for NSCLC outcomes. To this end, easily calculated functional features such as the maximum and the mean of standard uptake value (SUV) and total lesion glycolysis (TLG) are most commonly used for ...[more]

PMID: 31754135

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Project description:BackgroundDespite the fact that tumor microenvironment (TME) and gene mutations are the main determinants of progression of the deadliest cancer in the world - lung cancer, their interrelations are not well understood. Digital pathology data provides a unique insight into the spatial composition of the TME. Various spatial metrics and machine learning approaches were proposed for prediction of either patient survival or gene mutations from this data. Still, these approaches are limited in the scope of analyzed features and in their explainability, and as such fail to transfer to clinical practice.MethodsHere, we generated 23,199 image patches from 26 hematoxylin-and-eosin (H&E)-stained lung cancer tissue sections and annotated them into 9 different tissue classes. Using this dataset, we trained a deep neural network ARA-CNN. Next, we applied the trained network to segment 467 lung cancer H&E images from The Cancer Genome Atlas (TCGA) database. We used the segmented images to compute human-interpretable features reflecting the heterogeneous composition of the TME, and successfully utilized them to predict patient survival and cancer gene mutations.ResultsWe achieved per-class AUC ranging from 0.72 to 0.99 for classifying tissue types in lung cancer with ARA-CNN. Machine learning models trained on the proposed human-interpretable features achieved a c-index of 0.723 in the task of survival prediction and AUC up to 73.5% for PDGFRB in the task of mutation classification.ConclusionsWe presented a framework that accurately predicted survival and gene mutations in lung adenocarcinoma patients based on human-interpretable features extracted from H&E slides. Our approach can provide important insights for designing novel cancer treatments, by linking the spatial structure of the TME in lung adenocarcinoma to gene mutations and patient survival. It can also expand our understanding of the effects that the TME has on tumor evolutionary processes. Our approach can be generalized to different cancer types to inform precision medicine strategies.

Project description:Importance:There is a lack of studies exploring the performance of a deep learning survival neural network in non-small cell lung cancer (NSCLC). Objectives:To compare the performances of DeepSurv, a deep learning survival neural network with a tumor, node, and metastasis staging system in the prediction of survival and test the reliability of individual treatment recommendations provided by the deep learning survival neural network. Design, Setting, and Participants:In this population-based cohort study, a deep learning-based algorithm was developed and validated using consecutive cases of newly diagnosed stages I to IV NSCLC between January 2010 and December 2015 in a Surveillance, Epidemiology, and End Results database. A total of 127 features, including patient characteristics, tumor stage, and treatment strategies, were assessed for analysis. The algorithm was externally validated on an independent test cohort, comprising 1182 patients with stage I to III NSCLC diagnosed between January 2009 and December 2013 in Shanghai Pulmonary Hospital. Analysis began January 2018 and ended June 2019. Main Outcomes and Measures:The deep learning survival neural network model was compared with the tumor, node, and metastasis staging system for lung cancer-specific survival. The C statistic was used to assess the performance of models. A user-friendly interface was provided to facilitate the survival predictions and treatment recommendations of the deep learning survival neural network model. Results:Of 17 322 patients with NSCLC included in the study, 13 361 (77.1%) were white and the median (interquartile range) age was 68 (61-74) years. The majority of tumors were stage I disease (10 273 [59.3%]) and adenocarcinoma (11 985 [69.2%]). The median (interquartile range) follow-up time was 24 (10-43) months. There were 3119 patients who had lung cancer-related death during the follow-up period. The deep learning survival neural network model showed more promising results in the prediction of lung cancer-specific survival than the tumor, node, and metastasis stage on the test data set (C statistic = 0.739 vs 0.706). The population who received the recommended treatments had superior survival rates than those who received treatments not recommended (hazard ratio, 2.99; 95% CI, 2.49-3.59; P < .001), which was verified by propensity score-matched groups. The deep learning survival neural network model visualization was realized by a user-friendly graphic interface. Conclusions and Relevance:The deep learning survival neural network model shows potential benefits in prognostic evaluation and treatment recommendation with respect to lung cancer-specific survival. This novel analytical approach may provide reliable individual survival information and treatment recommendations.

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Deep segmentation networks predict survival of non-small cell lung cancer.

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Deep segmentation networks predict survival of non-small cell lung cancer.

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