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      Radiomics Study for Predicting the Expression of PD-L1 and Tumor Mutation Burden in Non-Small Cell Lung Cancer Based on CT Images and Clinicopathological Features

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          Abstract

          Background

          The present study compared the predictive performance of pretreatment computed tomography (CT)-based radiomics signatures and clinicopathological and CT morphological factors for ligand programmed death-ligand 1 (PD-L1) expression level and tumor mutation burden (TMB) status and further explored predictive models in patients with advanced-stage non-small cell lung cancer (NSCLC).

          Methods

          A total of 120 patients with advanced-stage NSCLC were enrolled in this retrospective study and randomly assigned to a training dataset or validation dataset. Here, 462 radiomics features were extracted from region-of-interest (ROI) segmentation based on pretreatment CT images. The least absolute shrinkage and selection operator (LASSO) and logistic regression were applied to select radiomics features and develop combined models with clinical and morphological factors for PD-L1 expression and TMB status prediction. Ten-fold cross-validation was used to evaluate the accuracy, and the predictive performance of these models was assessed using receiver operating characteristic (ROC) and area under the curve (AUC) analyses.

          Results

          The PD-L1-positive expression level correlated with differentiation degree (p = 0.005), tumor shape (p = 0.006), and vascular convergence (p = 0.007). Stage (p = 0.023), differentiation degree (p = 0.017), and vacuole sign (p = 0.016) were associated with TMB status. Radiomics signatures showed good performance for predicting PD-L1 and TMB with AUCs of 0.730 and 0.759, respectively. Predictive models that combined radiomics signatures with clinical and morphological factors dramatically improved the predictive efficacy for PD-L1 (AUC = 0.839) and TMB (p = 0.818). The results were verified in the validation datasets.

          Conclusions

          Quantitative CT-based radiomics features have potential value in the classification of PD-L1 expression levels and TMB status. The combined model further improved the predictive performance and provided sufficient information for the guiding of immunotherapy in clinical practice, and it deserves further analysis.

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          Most cited references71

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Regularization Paths for Generalized Linear Models via Coordinate Descent

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              pROC: an open-source package for R and S+ to analyze and compare ROC curves

              Background Receiver operating characteristic (ROC) curves are useful tools to evaluate classifiers in biomedical and bioinformatics applications. However, conclusions are often reached through inconsistent use or insufficient statistical analysis. To support researchers in their ROC curves analysis we developed pROC, a package for R and S+ that contains a set of tools displaying, analyzing, smoothing and comparing ROC curves in a user-friendly, object-oriented and flexible interface. Results With data previously imported into the R or S+ environment, the pROC package builds ROC curves and includes functions for computing confidence intervals, statistical tests for comparing total or partial area under the curve or the operating points of different classifiers, and methods for smoothing ROC curves. Intermediary and final results are visualised in user-friendly interfaces. A case study based on published clinical and biomarker data shows how to perform a typical ROC analysis with pROC. Conclusions pROC is a package for R and S+ specifically dedicated to ROC analysis. It proposes multiple statistical tests to compare ROC curves, and in particular partial areas under the curve, allowing proper ROC interpretation. pROC is available in two versions: in the R programming language or with a graphical user interface in the S+ statistical software. It is accessible at http://expasy.org/tools/pROC/ under the GNU General Public License. It is also distributed through the CRAN and CSAN public repositories, facilitating its installation.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                06 August 2021
                2021
                : 11
                : 620246
                Affiliations
                [1]Department of Radiation Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University , Jinan, China
                Author notes

                Edited by: Meiyappan Solaiyappan, Johns Hopkins University, United States

                Reviewed by: Jinming Yu, Shandong University, China; Qingtao Qiu, Shandong Cancer Hospital, China; Giuseppe Simone, Regina Elena National Cancer Institute (IRCCS), Italy

                *Correspondence: Zhe Yang, sdslyyyz@ 123456126.com

                This article was submitted to Cancer Imaging and Image-directed Interventions, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2021.620246
                8377473
                34422625
                87ed21fd-e637-44f8-ad82-cdb05739dd71
                Copyright © 2021 Wen, Yang, Dai, Feng and Li

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 October 2020
                : 20 July 2021
                Page count
                Figures: 3, Tables: 6, Equations: 0, References: 71, Pages: 12, Words: 6318
                Funding
                Funded by: Natural Science Foundation of Shandong Province 10.13039/501100007129
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                radiomics features,computed tomography,non-small cell lung cancer (nsclc),programmed death-ligand 1 (pd-l1),tumor mutation burden (tmb)

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