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      Radiomics as a personalized medicine tool in lung cancer: Separating the hope from the hype

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          Highlights

          • Radiomics studies in NSCLC suffer from a number of limitations.

          • No single radiomic signature has been translated into clinical use.

          • Identification of limitations can help future studies to expedite biomarker translation.

          Abstract

          Radiomics has become a popular image analysis method in the last few years. Its key hypothesis is that medical images harbor biological, prognostic and predictive information that is not revealed upon visual inspection. In contrast to previous work with a priori defined imaging biomarkers, radiomics instead calculates image features at scale and uses statistical methods to identify those most strongly associated to outcome. This builds on years of research into computer aided diagnosis and pattern recognition. While the potential of radiomics to aid personalized medicine is widely recognized, several technical limitations exist which hinder biomarker translation. Aspects of the radiomic workflow lack repeatability or reproducibility under particular circumstances, which is a key requirement for the translation of imaging biomarkers into clinical practice. One of the most commonly studied uses of radiomics is for personalized medicine applications in Non-Small Cell Lung Cancer (NSCLC). In this review, we summarize reported methodological limitations in CT based radiomic analyses together with suggested solutions. We then evaluate the current NSCLC radiomics literature to assess the risk associated with accepting the published conclusions with respect to these limitations. We review different complementary scoring systems and initiatives that can be used to critically appraise data from radiomics studies. Wider awareness should improve the quality of ongoing and future radiomics studies and advance their potential as clinically relevant biomarkers for personalized medicine in patients with NSCLC.

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          Most cited references102

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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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              Measuring Computed Tomography Scanner Variability of Radiomics Features.

              The purpose of this study was to determine the significance of interscanner variability in CT image radiomics studies.
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                Author and article information

                Contributors
                Journal
                Lung Cancer
                Lung Cancer
                Lung Cancer (Amsterdam, Netherlands)
                Elsevier Scientific Publishers
                0169-5002
                1872-8332
                1 August 2020
                August 2020
                : 146
                : 197-208
                Affiliations
                [a ]Division of Cancer Sciences, University of Manchester, Manchester, UK
                [b ]Department of Radiation Oncology, The Christie Hospital NHS Foundation Trust, Manchester, UK
                [c ]Department of Radiology, The Christie Hospital NHS Foundation Trust, Manchester, UK
                Author notes
                [* ]Corresponding author at: The University of Manchester, Division of Cancer Sciences, Wilmslow Road, Manchester, M20 4BX, UK. Isabella.fornacon-wood@ 123456postgrad.manchester.ac.uk
                [1]

                These authors contributed equally.

                Article
                S0169-5002(20)30452-9
                10.1016/j.lungcan.2020.05.028
                7383235
                32563015
                caa1a0c9-bc00-43fe-91f3-f87e030d41cf
                © 2020 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 March 2020
                : 18 May 2020
                : 23 May 2020
                Categories
                Article

                auc, area under the curve,ci, concordance index,hr, hazard ratio,roi, region of interest,rqs, radiomics quality score,tripod, transparent reporting of a multivariable prediction model for individual prognosis or diagnosis,radiomics,imaging biomarkers,lung cancer,personalized medicine

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