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      Peritumoral radiomics features predict distant metastasis in locally advanced NSCLC

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          Abstract

          Purpose

          Radiomics provides quantitative tissue heterogeneity profiling and is an exciting approach to developing imaging biomarkers in the context of precision medicine. Normal-appearing parenchymal tissues surrounding primary tumors can harbor microscopic disease that leads to increased risk of distant metastasis (DM). This study assesses whether computed-tomography (CT) imaging features of such peritumoral tissues can predict DM in locally advanced non-small cell lung cancer (NSCLC).

          Material and methods

          200 NSCLC patients of histological adenocarcinoma were included in this study. The investigated lung tissues were tumor rim, defined to be 3mm of tumor and parenchymal tissue on either side of the tumor border and the exterior region extended from 3 to 9mm outside of the tumor. Fifteen stable radiomic features were extracted and evaluated from each of these regions on pre-treatment CT images. For comparison, features from expert-delineated tumor contours were similarly prepared. The patient cohort was separated into training and validation datasets for prognostic power evaluation. Both univariable and multivariable analyses were performed for each region using concordance index (CI).

          Results

          Univariable analysis reveals that six out of fifteen tumor rim features were significantly prognostic of DM (p-value < 0.05), as were ten features from the visible tumor, and only one of the exterior features was. Multivariablely, a rim radiomic signature achieved the highest prognostic performance in the independent validation sub-cohort (CI = 0.64, p-value = 2.4×10 −5) significantly over a multivariable clinical model (CI = 0.53), a visible tumor radiomics model (CI = 0.59), or an exterior tissue model (CI = 0.55). Furthermore, patient stratification by the combined rim signature and clinical predictor led to a significant improvement on the clinical predictor alone and also outperformed stratification using the combined tumor signature and clinical predictor.

          Conclusions

          We identified peritumoral rim radiomic features significantly associated with DM. This study demonstrated that peritumoral imaging characteristics may provide additional valuable information over the visible tumor features for patient risk stratification due to cancer metastasis.

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          Most cited references25

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Microenvironmental regulation of metastasis.

            Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.
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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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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – original draft
                Role: Software
                Role: Software
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Project administration
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 November 2018
                2018
                : 13
                : 11
                : e0206108
                Affiliations
                [1 ] Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States of America
                [2 ] Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands
                Baylor College of Medicine, UNITED STATES
                Author notes

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

                Author information
                http://orcid.org/0000-0002-6153-8790
                Article
                PONE-D-18-18942
                10.1371/journal.pone.0206108
                6214508
                30388114
                c00c1b73-2f3c-4ac2-872c-ce8609b14455
                © 2018 Dou et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 June 2018
                : 5 October 2018
                Page count
                Figures: 4, Tables: 1, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: U24CA194354
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: U01CA190234
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007886, Dana-Farber Cancer Institute;
                Award Recipient :
                This work was supported by: the National Cancer Institute (Bethesda, United States) 2015-04 to 2020-03, Grant: U24CA194354 (HA) ( https://grants.uberresearch.com/100000054/U24CA194354/Quantitative-Radiomics-System-Decoding-the-Tumor-Phenotype); National Cancer Institute (Bethesda, United States) 2015-01 to 2019-12, Grant: U01CA190234 (HA)( https://grants.uberresearch.com/100000054/U01CA190234/Genotype-and-Imaging-Phenotype-Biomarkers-in-Lung-Cancer); and the Dana-Farber Cancer Institute (HA), the Kaye Scholar Award, and the DFCI Clinical-Translational Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Cancers and Neoplasms
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