skip to main content


Title: 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.  more » « less
Award ID(s):
1733742
NSF-PAR ID:
10390829
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Scientific Reports
Volume:
9
Issue:
1
ISSN:
2045-2322
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Background

    Lung cancer is the deadliest and second most common cancer in the United States due to the lack of symptoms for early diagnosis. Pulmonary nodules are small abnormal regions that can be potentially correlated to the occurrence of lung cancer. Early detection of these nodules is critical because it can significantly improve the patient's survival rates. Thoracic thin‐sliced computed tomography (CT) scanning has emerged as a widely used method for diagnosing and prognosis lung abnormalities.

    Purpose

    The standard clinical workflow of detecting pulmonary nodules relies on radiologists to analyze CT images to assess the risk factors of cancerous nodules. However, this approach can be error‐prone due to the various nodule formation causes, such as pollutants and infections. Deep learning (DL) algorithms have recently demonstrated remarkable success in medical image classification and segmentation. As an ever more important assistant to radiologists in nodule detection, it is imperative ensure the DL algorithm and radiologist to better understand the decisions from each other. This study aims to develop a framework integrating explainable AI methods to achieve accurate pulmonary nodule detection.

    Methods

    A robust and explainable detection (RXD) framework is proposed, focusing on reducing false positives in pulmonary nodule detection. Its implementation is based on an explanation supervision method, which uses nodule contours of radiologists as supervision signals to force the model to learn nodule morphologies, enabling improved learning ability on small dataset, and enable small dataset learning ability. In addition, two imputation methods are applied to the nodule region annotations to reduce the noise within human annotations and allow the model to have robust attributions that meet human expectations. The 480, 265, and 265 CT image sets from the public Lung Image Database Consortium and Image Database Resource Initiative (LIDC‐IDRI) dataset are used for training, validation, and testing.

    Results

    Using only 10, 30, 50, and 100 training samples sequentially, our method constantly improves the classification performance and explanation quality of baseline in terms of Area Under the Curve (AUC) and Intersection over Union (IoU). In particular, our framework with a learnable imputation kernel improves IoU from baseline by 24.0% to 80.0%. A pre‐defined Gaussian imputation kernel achieves an even greater improvement, from 38.4% to 118.8% from baseline. Compared to the baseline trained on 100 samples, our method shows less drop in AUC when trained on fewer samples. A comprehensive comparison of interpretability shows that our method aligns better with expert opinions.

    Conclusions

    A pulmonary nodule detection framework was demonstrated using public thoracic CT image datasets. The framework integrates the robust explanation supervision (RES) technique to ensure the performance of nodule classification and morphology. The method can reduce the workload of radiologists and enable them to focus on the diagnosis and prognosis of the potential cancerous pulmonary nodules at the early stage to improve the outcomes for lung cancer patients.

     
    more » « less
  2. null (Ed.)
    Positron emission tomography and computed tomography (PET-CT) dual-modality imaging provides critical diagnostic information in modern cancer diagnosis and therapy. Automated accurate tumor delineation is essentially important in computer-assisted tumor reading and interpretation based on PET-CT. In this paper, we propose a novel approach for the segmentation of lung tumors that combines the powerful fully convolutional networks (FCN) based semantic segmentation framework (3D-UNet) and the graph cut based co-segmentation model. First, two separate deep UNets are trained on PET and CT, separately, to learn high level discriminative features to generate tumor/non-tumor masks and probability maps for PET and CT images. Then, the two probability maps on PET and CT are further simultaneously employed in a graph cut based co-segmentation model to produce the final tumor segmentation results. Comparative experiments on 32 PET-CT scans of lung cancer patients demonstrate the effectiveness of our method. 
    more » « less
  3. null (Ed.)
    Positron emission tomography and computed tomography (PET-CT) plays a critically important role in modern cancer therapy. In this paper, we focus on automated tumor delineation on PET-CT image pairs. Inspired by co-segmentation model, we develop a novel 3D image co-matting technique making use of the inner-modality information of PET and CT for matting. The obtained co-matting results are then incorporated in the graph-cut based PET-CT co-segmentation framework. Our comparative experiments on 32 PET-CT scan pairs of lung cancer patients demonstrate that the proposed 3D image co-matting technique can significantly improve the quality of cost images for the co-segmentation, resulting in highly accurate tumor segmentation on both PET and CT scan pairs. 
    more » « less
  4. In this paper, we present a model to obtain prior knowledge for organ localization in CT thorax images using three dimensional convolutional neural networks (3D CNNs). Specifically, we use the knowledge obtained from CNNs in a Bayesian detector to establish the presence and location of a given target organ defined within a spherical coordinate system. We train a CNN to perform a soft detection of the target organ potentially present at any point, x = [r,Θ,Φ]T. This probability outcome is used as a prior in a Bayesian model whose posterior probability serves to provide a more accurate solution to the target organ detection problem. The likelihoods for the Bayesian model are obtained by performing a spatial analysis of the organs in annotated training volumes. Thoracic CT images from the NSCLC–Radiomics dataset are used in our case study, which demonstrates the enhancement in robustness and accuracy of organ identification. The average value of the detector accuracies for the right lung, left lung, and heart were found to be 94.87%, 95.37%, and 90.76% after the CNN stage, respectively. Introduction of spatial relationship using a Bayes classifier improved the detector accuracies to 95.14%, 96.20%, and 95.15%, respectively, showing a marked improvement in heart detection. This workflow improves the detection rate since the decision is made employing both lower level features (edges, contour etc) and complex higher level features (spatial relationship between organs). This strategy also presents a new application to CNNs and a novel methodology to introduce higher level context features like spatial relationship between objects present at a different location in images to real world object detection problems. 
    more » « less
  5. null (Ed.)
    Abstract Background Interstitial lung abnormalities (ILA) can be detected on computed tomography (CT) in lung cancer patients and have an association with mortality in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study is to demonstrate the significance of ILA for mortality in patients with stage I NSCLC using Boston Lung Cancer Study cohort. Methods Two hundred and thirty-one patients with stage I NSCLC from 2000 to 2011 were investigated in this retrospective study (median age, 69 years; 93 males, 138 females). ILA was scored on baseline CT scans prior to treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA) by a sequential reading method. ILA score 2 was considered the presence of ILA. The difference of overall survival (OS) for patients with different ILA scores were tested via log-rank test and multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) including ILA score, age, sex, smoking status, and treatment as the confounding variables. Results ILA was present in 22 out of 231 patients (9.5%) with stage I NSCLC. The presence of ILA was associated with shorter OS (patients with ILA score 2, median 3.85 years [95% confidence interval (CI): 3.36 – not reached (NR)]; patients with ILA score 0 or 1, median 10.16 years [95%CI: 8.65 - NR]; P  <  0.0001). In a Cox proportional hazards model, the presence of ILA remained significant for increased risk for death (HR = 2.88, P  = 0.005) after adjusting for age, sex, smoking and treatment. Conclusions ILA was detected on CT in 9.5% of patients with stage I NSCLC. The presence of ILA was significantly associated with a shorter OS and could be an imaging marker of shorter survival in stage I NSCLC. 
    more » « less