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      Lung tumor segmentation methods: Impact on the uncertainty of radiomics features for non-small cell lung cancer

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          Abstract

          Purpose

          To evaluate the uncertainty of radiomics features from contrast-enhanced breath-hold helical CT scans of non-small cell lung cancer for both manual and semi-automatic segmentation due to intra-observer, inter-observer, and inter-software reliability.

          Methods

          Three radiation oncologists manually delineated lung tumors twice from 10 CT scans using two software tools (3D-Slicer and MIM Maestro). Additionally, three observers without formal clinical training were instructed to use two semi-automatic segmentation tools, Lesion Sizing Toolkit (LSTK) and GrowCut, to delineate the same tumor volumes. The accuracy of the semi-automatic contours was assessed by comparison with physician manual contours using Dice similarity coefficients and Hausdorff distances. Eighty-three radiomics features were calculated for each delineated tumor contour. Informative features were identified based on their dynamic range and correlation to other features. Feature reliability was then evaluated using intra-class correlation coefficients (ICC). Feature range was used to evaluate the uncertainty of the segmentation methods.

          Results

          From the initial set of 83 features, 40 radiomics features were found to be informative, and these 40 features were used in the subsequent analyses. For both intra-observer and inter-observer reliability, LSTK had higher reliability than GrowCut and the two manual segmentation tools. All observers achieved consistently high ICC values when using LSTK, but the ICC value varied greatly for each observer when using GrowCut and the manual segmentation tools. For inter-software reliability, features were not reproducible across the software tools for either manual or semi-automatic segmentation methods. Additionally, no feature category was found to be more reproducible than another feature category. Feature ranges of LSTK contours were smaller than those of manual contours for all features.

          Conclusion

          Radiomics features extracted from LSTK contours were highly reliable across and among observers. With semi-automatic segmentation tools, observers without formal clinical training were comparable to physicians in evaluating tumor segmentation.

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          Most cited references28

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          Radiomics Signature: A Potential Biomarker for the Prediction of Disease-Free Survival in Early-Stage (I or II) Non-Small Cell Lung Cancer.

          Purpose To develop a radiomics signature to estimate disease-free survival (DFS) in patients with early-stage (stage I-II) non-small cell lung cancer (NSCLC) and assess its incremental value to the traditional staging system and clinical-pathologic risk factors for individual DFS estimation. Materials and Methods Ethical approval by the institutional review board was obtained for this retrospective analysis, and the need to obtain informed consent was waived. This study consisted of 282 consecutive patients with stage IA-IIB NSCLC. A radiomics signature was generated by using the least absolute shrinkage and selection operator, or LASSO, Cox regression model. Association between the radiomics signature and DFS was explored. Further validation of the radiomics signature as an independent biomarker was performed by using multivariate Cox regression. A radiomics nomogram with the radiomics signature incorporated was constructed to demonstrate the incremental value of the radiomics signature to the traditional staging system and other clinical-pathologic risk factors for individualized DFS estimation, which was then assessed with respect to calibration, discrimination, reclassification, and clinical usefulness. Results The radiomics signature was significantly associated with DFS, independent of clinical-pathologic risk factors. Incorporating the radiomics signature into the radiomics-based nomogram resulted in better performance (P < .0001) for the estimation of DFS (C-index: 0.72; 95% confidence interval [CI]: 0.71, 0.73) than with the clinical-pathologic nomogram (C-index: 0.691; 95% CI: 0.68, 0.70), as well as a better calibration and improved accuracy of the classification of survival outcomes (net reclassification improvement: 0.182; 95% CI: 0.02, 0.31; P = .02). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinical-pathologic nomogram. Conclusion The radiomics signature is an independent biomarker for the estimation of DFS in patients with early-stage NSCLC. Combination of the radiomics signature, traditional staging system, and other clinical-pathologic risk factors performed better for individualized DFS estimation in patients with early-stage NSCLC, which might enable a step forward precise medicine. (©) RSNA, 2016 Online supplemental material is available for this article.
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            Method agreement analysis: a review of correct methodology.

            The correct approach to analyzing method agreement is discussed. Whether we are considering agreement between two measurements on the same samples (repeatability) or two individuals using identical methodology on identical samples (reproducibility) or comparing two methods, appropriate procedures are described, and worked examples are shown. The correct approaches for both categorical and numerical variables are explained. More complex analyses involving a comparison of more than two pairs of data are mentioned and guidance for these analyses given. Simple formulae for calculating the approximate sample size needed for agreement analysis are also given. Examples of good practice from the reproduction literature are cited, and common errors of methodology are indicated. 2010 Elsevier Inc. All rights reserved.
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              Reliability, repeatability and reproducibility: analysis of measurement errors in continuous variables.

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: ResourcesRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: ResourcesRole: Writing – review & editing
                Role: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 October 2018
                2018
                : 13
                : 10
                : e0205003
                Affiliations
                [1 ] Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
                [2 ] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, United States of America
                [3 ] Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
                [4 ] Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
                [5 ] Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
                [6 ] Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
                University of Pennsylvania Perelman School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-7208-394X
                http://orcid.org/0000-0002-2557-5340
                http://orcid.org/0000-0002-8090-2770
                http://orcid.org/0000-0002-9254-4501
                Article
                PONE-D-18-13467
                10.1371/journal.pone.0205003
                6171919
                30286184
                2911b0f1-c261-4fe0-8a5d-015c068ab152

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 4 May 2018
                : 18 September 2018
                Page count
                Figures: 13, Tables: 2, Pages: 22
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100004917, Cancer Prevention and Research Institute of Texas;
                Award ID: RP110562
                Award Recipient :
                Funded by: National Institutes of Health through Cancer Center Support Grant
                Award ID: P30CA016672
                Award Recipient :
                The authors acknowledge financial support from the Cancer Prevention Research Institute of Texas (URL: http://www.cprit.state.tx.us/) grant under award number RP110562. J.Y. and L.C. are the authors that received this fund. The authors acknowledge financial support from the National Institutes of Health/National Cancer Institute (URL: https://cancercenters.cancer.gov/) through Cancer Center Support Grant under award number P30 CA016672. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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