Radiomic Profiling of Glioblastoma: Identifying an Imaging Predictor of Patient Survival with Improved Performance over Established Clinical and Radiologic Risk Models
Purpose To evaluate whether radiomic feature-based magnetic resonance (MR) imaging signatures allow prediction of survival and stratification of patients with newly diagnosed glioblastoma with improved accuracy compared with that of established clinical and radiologic risk models. Materials and Meth...
Gespeichert in:
Veröffentlicht in: | Radiology 2016-09, Vol.280 (3), p.880-889 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 889 |
---|---|
container_issue | 3 |
container_start_page | 880 |
container_title | Radiology |
container_volume | 280 |
creator | Kickingereder, Philipp Burth, Sina Wick, Antje Götz, Michael Eidel, Oliver Schlemmer, Heinz-Peter Maier-Hein, Klaus H Wick, Wolfgang Bendszus, Martin Radbruch, Alexander Bonekamp, David |
description | Purpose To evaluate whether radiomic feature-based magnetic resonance (MR) imaging signatures allow prediction of survival and stratification of patients with newly diagnosed glioblastoma with improved accuracy compared with that of established clinical and radiologic risk models. Materials and Methods Retrospective evaluation of data was approved by the local ethics committee and informed consent was waived. A total of 119 patients (allocated in a 2:1 ratio to a discovery [n = 79] or validation [n = 40] set) with newly diagnosed glioblastoma were subjected to radiomic feature extraction (12 190 features extracted, including first-order, volume, shape, and texture features) from the multiparametric (contrast material-enhanced T1-weighted and fluid-attenuated inversion-recovery imaging sequences) and multiregional (contrast-enhanced and unenhanced) tumor volumes. Radiomic features of patients in the discovery set were subjected to a supervised principal component (SPC) analysis to predict progression-free survival (PFS) and overall survival (OS) and were validated in the validation set. The performance of a Cox proportional hazards model with the SPC analysis predictor was assessed with C index and integrated Brier scores (IBS, lower scores indicating higher accuracy) and compared with Cox models based on clinical (age and Karnofsky performance score) and radiologic (Gaussian normalized relative cerebral blood volume and apparent diffusion coefficient) parameters. Results SPC analysis allowed stratification based on 11 features of patients in the discovery set into a low- or high-risk group for PFS (hazard ratio [HR], 2.43; P = .002) and OS (HR, 4.33; P < .001), and the results were validated successfully in the validation set for PFS (HR, 2.28; P = .032) and OS (HR, 3.45; P = .004). The performance of the SPC analysis (OS: IBS, 0.149; C index, 0.654; PFS: IBS, 0.138; C index, 0.611) was higher compared with that of the radiologic (OS: IBS, 0.175; C index, 0.603; PFS: IBS, 0.149; C index, 0.554) and clinical risk models (OS: IBS, 0.161, C index, 0.640; PFS: IBS, 0.139; C index, 0.599). The performance of the SPC analysis model was further improved when combined with clinical data (OS: IBS, 0.142; C index, 0.696; PFS: IBS, 0.132; C index, 0.637). Conclusion An 11-feature radiomic signature that allows prediction of survival and stratification of patients with newly diagnosed glioblastoma was identified, and improved performance compared with that of establis |
doi_str_mv | 10.1148/radiol.2016160845 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1812891208</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1812891208</sourcerecordid><originalsourceid>FETCH-LOGICAL-c344t-1848a75a03e0c34d36989179d356d12b0147832ef5199b838caf2aad61e88c2d3</originalsourceid><addsrcrecordid>eNpFUU1PGzEQtVARpMAP4FL52MumHns_vL1VUaCRqBoFOK9mbW8w9a6pvQniF_Vv1ttQOM1o5r03T_MIuQQ2B8jll4DaejfnDEoomcyLIzKDglcZCCg-kBljQmQyh_qUfIzxkTHIC1mdkFNeCV6WZTEjfzaTRm8VXQffWWeHLfUdvXbWtw7j6Hv8SlfaDKPtXqYlDnTV43Zq18Foq0YfJsYaR5tQ9HYX9naPjj7b8SFBn4LfG03XJnQ-9DgoQ9Mg0GUcsXU2PqTlIp21KnFw0PSfIee3ydLGxl_0h9fGxXNy3KGL5uK1npH7q-Xd4nt28_N6tfh2kymR52MGMpdYFciEYWmiRVnLGqpai6LUwNv0gUoKbroC6rqVQirsOKIuwUipuBZn5PNBN_n-vTNxbHoblXEOB-N3sQEJPClyJhMUDlAVfIzBdM1TsD2GlwZYM-XTHPJp3vNJnE-v8ru2N_qN8T8Q8Rd0Co-C</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1812891208</pqid></control><display><type>article</type><title>Radiomic Profiling of Glioblastoma: Identifying an Imaging Predictor of Patient Survival with Improved Performance over Established Clinical and Radiologic Risk Models</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Kickingereder, Philipp ; Burth, Sina ; Wick, Antje ; Götz, Michael ; Eidel, Oliver ; Schlemmer, Heinz-Peter ; Maier-Hein, Klaus H ; Wick, Wolfgang ; Bendszus, Martin ; Radbruch, Alexander ; Bonekamp, David</creator><creatorcontrib>Kickingereder, Philipp ; Burth, Sina ; Wick, Antje ; Götz, Michael ; Eidel, Oliver ; Schlemmer, Heinz-Peter ; Maier-Hein, Klaus H ; Wick, Wolfgang ; Bendszus, Martin ; Radbruch, Alexander ; Bonekamp, David</creatorcontrib><description>Purpose To evaluate whether radiomic feature-based magnetic resonance (MR) imaging signatures allow prediction of survival and stratification of patients with newly diagnosed glioblastoma with improved accuracy compared with that of established clinical and radiologic risk models. Materials and Methods Retrospective evaluation of data was approved by the local ethics committee and informed consent was waived. A total of 119 patients (allocated in a 2:1 ratio to a discovery [n = 79] or validation [n = 40] set) with newly diagnosed glioblastoma were subjected to radiomic feature extraction (12 190 features extracted, including first-order, volume, shape, and texture features) from the multiparametric (contrast material-enhanced T1-weighted and fluid-attenuated inversion-recovery imaging sequences) and multiregional (contrast-enhanced and unenhanced) tumor volumes. Radiomic features of patients in the discovery set were subjected to a supervised principal component (SPC) analysis to predict progression-free survival (PFS) and overall survival (OS) and were validated in the validation set. The performance of a Cox proportional hazards model with the SPC analysis predictor was assessed with C index and integrated Brier scores (IBS, lower scores indicating higher accuracy) and compared with Cox models based on clinical (age and Karnofsky performance score) and radiologic (Gaussian normalized relative cerebral blood volume and apparent diffusion coefficient) parameters. Results SPC analysis allowed stratification based on 11 features of patients in the discovery set into a low- or high-risk group for PFS (hazard ratio [HR], 2.43; P = .002) and OS (HR, 4.33; P < .001), and the results were validated successfully in the validation set for PFS (HR, 2.28; P = .032) and OS (HR, 3.45; P = .004). The performance of the SPC analysis (OS: IBS, 0.149; C index, 0.654; PFS: IBS, 0.138; C index, 0.611) was higher compared with that of the radiologic (OS: IBS, 0.175; C index, 0.603; PFS: IBS, 0.149; C index, 0.554) and clinical risk models (OS: IBS, 0.161, C index, 0.640; PFS: IBS, 0.139; C index, 0.599). The performance of the SPC analysis model was further improved when combined with clinical data (OS: IBS, 0.142; C index, 0.696; PFS: IBS, 0.132; C index, 0.637). Conclusion An 11-feature radiomic signature that allows prediction of survival and stratification of patients with newly diagnosed glioblastoma was identified, and improved performance compared with that of established clinical and radiologic risk models was demonstrated. (©) RSNA, 2016 Online supplemental material is available for this article.</description><identifier>ISSN: 0033-8419</identifier><identifier>EISSN: 1527-1315</identifier><identifier>DOI: 10.1148/radiol.2016160845</identifier><identifier>PMID: 27326665</identifier><language>eng</language><publisher>United States</publisher><subject>Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - pathology ; Contrast Media ; Female ; Germany ; Glioblastoma - diagnostic imaging ; Glioblastoma - pathology ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging - methods ; Male ; Meglumine ; Organometallic Compounds ; Predictive Value of Tests ; Retrospective Studies ; Risk Assessment ; Survival Rate ; Tumor Burden</subject><ispartof>Radiology, 2016-09, Vol.280 (3), p.880-889</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-1848a75a03e0c34d36989179d356d12b0147832ef5199b838caf2aad61e88c2d3</citedby><cites>FETCH-LOGICAL-c344t-1848a75a03e0c34d36989179d356d12b0147832ef5199b838caf2aad61e88c2d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27326665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kickingereder, Philipp</creatorcontrib><creatorcontrib>Burth, Sina</creatorcontrib><creatorcontrib>Wick, Antje</creatorcontrib><creatorcontrib>Götz, Michael</creatorcontrib><creatorcontrib>Eidel, Oliver</creatorcontrib><creatorcontrib>Schlemmer, Heinz-Peter</creatorcontrib><creatorcontrib>Maier-Hein, Klaus H</creatorcontrib><creatorcontrib>Wick, Wolfgang</creatorcontrib><creatorcontrib>Bendszus, Martin</creatorcontrib><creatorcontrib>Radbruch, Alexander</creatorcontrib><creatorcontrib>Bonekamp, David</creatorcontrib><title>Radiomic Profiling of Glioblastoma: Identifying an Imaging Predictor of Patient Survival with Improved Performance over Established Clinical and Radiologic Risk Models</title><title>Radiology</title><addtitle>Radiology</addtitle><description>Purpose To evaluate whether radiomic feature-based magnetic resonance (MR) imaging signatures allow prediction of survival and stratification of patients with newly diagnosed glioblastoma with improved accuracy compared with that of established clinical and radiologic risk models. Materials and Methods Retrospective evaluation of data was approved by the local ethics committee and informed consent was waived. A total of 119 patients (allocated in a 2:1 ratio to a discovery [n = 79] or validation [n = 40] set) with newly diagnosed glioblastoma were subjected to radiomic feature extraction (12 190 features extracted, including first-order, volume, shape, and texture features) from the multiparametric (contrast material-enhanced T1-weighted and fluid-attenuated inversion-recovery imaging sequences) and multiregional (contrast-enhanced and unenhanced) tumor volumes. Radiomic features of patients in the discovery set were subjected to a supervised principal component (SPC) analysis to predict progression-free survival (PFS) and overall survival (OS) and were validated in the validation set. The performance of a Cox proportional hazards model with the SPC analysis predictor was assessed with C index and integrated Brier scores (IBS, lower scores indicating higher accuracy) and compared with Cox models based on clinical (age and Karnofsky performance score) and radiologic (Gaussian normalized relative cerebral blood volume and apparent diffusion coefficient) parameters. Results SPC analysis allowed stratification based on 11 features of patients in the discovery set into a low- or high-risk group for PFS (hazard ratio [HR], 2.43; P = .002) and OS (HR, 4.33; P < .001), and the results were validated successfully in the validation set for PFS (HR, 2.28; P = .032) and OS (HR, 3.45; P = .004). The performance of the SPC analysis (OS: IBS, 0.149; C index, 0.654; PFS: IBS, 0.138; C index, 0.611) was higher compared with that of the radiologic (OS: IBS, 0.175; C index, 0.603; PFS: IBS, 0.149; C index, 0.554) and clinical risk models (OS: IBS, 0.161, C index, 0.640; PFS: IBS, 0.139; C index, 0.599). The performance of the SPC analysis model was further improved when combined with clinical data (OS: IBS, 0.142; C index, 0.696; PFS: IBS, 0.132; C index, 0.637). Conclusion An 11-feature radiomic signature that allows prediction of survival and stratification of patients with newly diagnosed glioblastoma was identified, and improved performance compared with that of established clinical and radiologic risk models was demonstrated. (©) RSNA, 2016 Online supplemental material is available for this article.</description><subject>Brain Neoplasms - diagnostic imaging</subject><subject>Brain Neoplasms - pathology</subject><subject>Contrast Media</subject><subject>Female</subject><subject>Germany</subject><subject>Glioblastoma - diagnostic imaging</subject><subject>Glioblastoma - pathology</subject><subject>Humans</subject><subject>Image Interpretation, Computer-Assisted</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Male</subject><subject>Meglumine</subject><subject>Organometallic Compounds</subject><subject>Predictive Value of Tests</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Survival Rate</subject><subject>Tumor Burden</subject><issn>0033-8419</issn><issn>1527-1315</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUU1PGzEQtVARpMAP4FL52MumHns_vL1VUaCRqBoFOK9mbW8w9a6pvQniF_Vv1ttQOM1o5r03T_MIuQQ2B8jll4DaejfnDEoomcyLIzKDglcZCCg-kBljQmQyh_qUfIzxkTHIC1mdkFNeCV6WZTEjfzaTRm8VXQffWWeHLfUdvXbWtw7j6Hv8SlfaDKPtXqYlDnTV43Zq18Foq0YfJsYaR5tQ9HYX9naPjj7b8SFBn4LfG03XJnQ-9DgoQ9Mg0GUcsXU2PqTlIp21KnFw0PSfIee3ydLGxl_0h9fGxXNy3KGL5uK1npH7q-Xd4nt28_N6tfh2kymR52MGMpdYFciEYWmiRVnLGqpai6LUwNv0gUoKbroC6rqVQirsOKIuwUipuBZn5PNBN_n-vTNxbHoblXEOB-N3sQEJPClyJhMUDlAVfIzBdM1TsD2GlwZYM-XTHPJp3vNJnE-v8ru2N_qN8T8Q8Rd0Co-C</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Kickingereder, Philipp</creator><creator>Burth, Sina</creator><creator>Wick, Antje</creator><creator>Götz, Michael</creator><creator>Eidel, Oliver</creator><creator>Schlemmer, Heinz-Peter</creator><creator>Maier-Hein, Klaus H</creator><creator>Wick, Wolfgang</creator><creator>Bendszus, Martin</creator><creator>Radbruch, Alexander</creator><creator>Bonekamp, David</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201609</creationdate><title>Radiomic Profiling of Glioblastoma: Identifying an Imaging Predictor of Patient Survival with Improved Performance over Established Clinical and Radiologic Risk Models</title><author>Kickingereder, Philipp ; Burth, Sina ; Wick, Antje ; Götz, Michael ; Eidel, Oliver ; Schlemmer, Heinz-Peter ; Maier-Hein, Klaus H ; Wick, Wolfgang ; Bendszus, Martin ; Radbruch, Alexander ; Bonekamp, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-1848a75a03e0c34d36989179d356d12b0147832ef5199b838caf2aad61e88c2d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Brain Neoplasms - diagnostic imaging</topic><topic>Brain Neoplasms - pathology</topic><topic>Contrast Media</topic><topic>Female</topic><topic>Germany</topic><topic>Glioblastoma - diagnostic imaging</topic><topic>Glioblastoma - pathology</topic><topic>Humans</topic><topic>Image Interpretation, Computer-Assisted</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Male</topic><topic>Meglumine</topic><topic>Organometallic Compounds</topic><topic>Predictive Value of Tests</topic><topic>Retrospective Studies</topic><topic>Risk Assessment</topic><topic>Survival Rate</topic><topic>Tumor Burden</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kickingereder, Philipp</creatorcontrib><creatorcontrib>Burth, Sina</creatorcontrib><creatorcontrib>Wick, Antje</creatorcontrib><creatorcontrib>Götz, Michael</creatorcontrib><creatorcontrib>Eidel, Oliver</creatorcontrib><creatorcontrib>Schlemmer, Heinz-Peter</creatorcontrib><creatorcontrib>Maier-Hein, Klaus H</creatorcontrib><creatorcontrib>Wick, Wolfgang</creatorcontrib><creatorcontrib>Bendszus, Martin</creatorcontrib><creatorcontrib>Radbruch, Alexander</creatorcontrib><creatorcontrib>Bonekamp, David</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Radiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kickingereder, Philipp</au><au>Burth, Sina</au><au>Wick, Antje</au><au>Götz, Michael</au><au>Eidel, Oliver</au><au>Schlemmer, Heinz-Peter</au><au>Maier-Hein, Klaus H</au><au>Wick, Wolfgang</au><au>Bendszus, Martin</au><au>Radbruch, Alexander</au><au>Bonekamp, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Radiomic Profiling of Glioblastoma: Identifying an Imaging Predictor of Patient Survival with Improved Performance over Established Clinical and Radiologic Risk Models</atitle><jtitle>Radiology</jtitle><addtitle>Radiology</addtitle><date>2016-09</date><risdate>2016</risdate><volume>280</volume><issue>3</issue><spage>880</spage><epage>889</epage><pages>880-889</pages><issn>0033-8419</issn><eissn>1527-1315</eissn><abstract>Purpose To evaluate whether radiomic feature-based magnetic resonance (MR) imaging signatures allow prediction of survival and stratification of patients with newly diagnosed glioblastoma with improved accuracy compared with that of established clinical and radiologic risk models. Materials and Methods Retrospective evaluation of data was approved by the local ethics committee and informed consent was waived. A total of 119 patients (allocated in a 2:1 ratio to a discovery [n = 79] or validation [n = 40] set) with newly diagnosed glioblastoma were subjected to radiomic feature extraction (12 190 features extracted, including first-order, volume, shape, and texture features) from the multiparametric (contrast material-enhanced T1-weighted and fluid-attenuated inversion-recovery imaging sequences) and multiregional (contrast-enhanced and unenhanced) tumor volumes. Radiomic features of patients in the discovery set were subjected to a supervised principal component (SPC) analysis to predict progression-free survival (PFS) and overall survival (OS) and were validated in the validation set. The performance of a Cox proportional hazards model with the SPC analysis predictor was assessed with C index and integrated Brier scores (IBS, lower scores indicating higher accuracy) and compared with Cox models based on clinical (age and Karnofsky performance score) and radiologic (Gaussian normalized relative cerebral blood volume and apparent diffusion coefficient) parameters. Results SPC analysis allowed stratification based on 11 features of patients in the discovery set into a low- or high-risk group for PFS (hazard ratio [HR], 2.43; P = .002) and OS (HR, 4.33; P < .001), and the results were validated successfully in the validation set for PFS (HR, 2.28; P = .032) and OS (HR, 3.45; P = .004). The performance of the SPC analysis (OS: IBS, 0.149; C index, 0.654; PFS: IBS, 0.138; C index, 0.611) was higher compared with that of the radiologic (OS: IBS, 0.175; C index, 0.603; PFS: IBS, 0.149; C index, 0.554) and clinical risk models (OS: IBS, 0.161, C index, 0.640; PFS: IBS, 0.139; C index, 0.599). The performance of the SPC analysis model was further improved when combined with clinical data (OS: IBS, 0.142; C index, 0.696; PFS: IBS, 0.132; C index, 0.637). Conclusion An 11-feature radiomic signature that allows prediction of survival and stratification of patients with newly diagnosed glioblastoma was identified, and improved performance compared with that of established clinical and radiologic risk models was demonstrated. (©) RSNA, 2016 Online supplemental material is available for this article.</abstract><cop>United States</cop><pmid>27326665</pmid><doi>10.1148/radiol.2016160845</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0033-8419 |
ispartof | Radiology, 2016-09, Vol.280 (3), p.880-889 |
issn | 0033-8419 1527-1315 |
language | eng |
recordid | cdi_proquest_miscellaneous_1812891208 |
source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
subjects | Brain Neoplasms - diagnostic imaging Brain Neoplasms - pathology Contrast Media Female Germany Glioblastoma - diagnostic imaging Glioblastoma - pathology Humans Image Interpretation, Computer-Assisted Magnetic Resonance Imaging - methods Male Meglumine Organometallic Compounds Predictive Value of Tests Retrospective Studies Risk Assessment Survival Rate Tumor Burden |
title | Radiomic Profiling of Glioblastoma: Identifying an Imaging Predictor of Patient Survival with Improved Performance over Established Clinical and Radiologic Risk Models |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T21%3A41%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Radiomic%20Profiling%20of%20Glioblastoma:%20Identifying%20an%20Imaging%20Predictor%20of%20Patient%20Survival%20with%20Improved%20Performance%20over%20Established%20Clinical%20and%20Radiologic%20Risk%20Models&rft.jtitle=Radiology&rft.au=Kickingereder,%20Philipp&rft.date=2016-09&rft.volume=280&rft.issue=3&rft.spage=880&rft.epage=889&rft.pages=880-889&rft.issn=0033-8419&rft.eissn=1527-1315&rft_id=info:doi/10.1148/radiol.2016160845&rft_dat=%3Cproquest_cross%3E1812891208%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1812891208&rft_id=info:pmid/27326665&rfr_iscdi=true |