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      Radiomics-based Prognosis Analysis for Non-Small Cell Lung Cancer

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          Abstract

          Radiomics characterizes tumor phenotypes by extracting large numbers of quantitative features from radiological images. Radiomic features have been shown to provide prognostic value in predicting clinical outcomes in several studies. However, several challenges including feature redundancy, unbalanced data, and small sample sizes have led to relatively low predictive accuracy. In this study, we explore different strategies for overcoming these challenges and improving predictive performance of radiomics-based prognosis for non-small cell lung cancer (NSCLC). CT images of 112 patients (mean age 75 years) with NSCLC who underwent stereotactic body radiotherapy were used to predict recurrence, death, and recurrence-free survival using a comprehensive radiomics analysis. Different feature selection and predictive modeling techniques were used to determine the optimal configuration of prognosis analysis. To address feature redundancy, comprehensive analysis indicated that Random Forest models and Principal Component Analysis were optimum predictive modeling and feature selection methods, respectively, for achieving high prognosis performance. To address unbalanced data, Synthetic Minority Over-sampling technique was found to significantly increase predictive accuracy. A full analysis of variance showed that data endpoints, feature selection techniques, and classifiers were significant factors in affecting predictive accuracy, suggesting that these factors must be investigated when building radiomics-based predictive models for cancer prognosis.

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          Machine Learning methods for Quantitative Radiomic Biomarkers

          Radiomics extracts and mines large number of medical imaging features quantifying tumor phenotypic characteristics. Highly accurate and reliable machine-learning approaches can drive the success of radiomic applications in clinical care. In this radiomic study, fourteen feature selection methods and twelve classification methods were examined in terms of their performance and stability for predicting overall survival. A total of 440 radiomic features were extracted from pre-treatment computed tomography (CT) images of 464 lung cancer patients. To ensure the unbiased evaluation of different machine-learning methods, publicly available implementations along with reported parameter configurations were used. Furthermore, we used two independent radiomic cohorts for training (n = 310 patients) and validation (n = 154 patients). We identified that Wilcoxon test based feature selection method WLCX (stability = 0.84 ± 0.05, AUC = 0.65 ± 0.02) and a classification method random forest RF (RSD = 3.52%, AUC = 0.66 ± 0.03) had highest prognostic performance with high stability against data perturbation. Our variability analysis indicated that the choice of classification method is the most dominant source of performance variation (34.21% of total variance). Identification of optimal machine-learning methods for radiomic applications is a crucial step towards stable and clinically relevant radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor-phenotypic characteristics in clinical practice.
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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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              GLUMIP 2.0: SAS/IML Software for Planning Internal Pilots.

              Internal pilot designs involve conducting interim power analysis (without interim data analysis) to modify the final sample size. Recently developed techniques have been described to avoid the type I error rate inflation inherent to unadjusted hypothesis tests, while still providing the advantages of an internal pilot design. We present GLUMIP 2.0, the latest version of our free SAS/IML software for planning internal pilot studies in the general linear univariate model (GLUM) framework. The new analytic forms incorporated into the updated software solve many problems inherent to current internal pilot techniques for linear models with Gaussian errors. Hence, the GLUMIP 2.0 software makes it easy to perform exact power analysis for internal pilots under the GLUM framework with independent Gaussian errors and fixed predictors.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                18 April 2017
                2017
                : 7
                : 46349
                Affiliations
                [1 ]Dept. of Medical Imaging, Sunnybrook Research Institute, University of Toronto , Toronto, ON, Canada
                [2 ]Dept. of Systems Design Engineering, University of Waterloo , Waterloo, ON, Canada
                Author notes
                Article
                srep46349
                10.1038/srep46349
                5394465
                28418006
                80546316-8061-415b-9f32-5182a038e978
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 07 November 2016
                : 14 March 2017
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