Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study

Background Bayesian networks (BNs) are machine-learning–based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node me...

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Autores: Reijnen, Casper, Gogou, Evangelia, Visser, Nicole C. M., Engerud, Hilde, Ramjith, Jordache, van der Putten, Louis J. M., van de Vijver, Koen, Santacana Espasa, Maria, Bronsert, Peter, Bulten, Johan, Hirschfeld, Marc, Colás, Eva, Gil-Moreno, Antonio, Reques, Armando, Mancebo, Gemma, Krakstad, Camilla, Trovik, Jone, Haldorsen, Ingfrid S., Huvila, Jutta, Koskas, Martin, Weinberger, Vit, Bednaříková, Markéta, Hausnerova, Jitka, van der Wurff, Anneke A. M., Matias-Guiu, Xavier, Amant, Frederic, Massuger, Leon F. A. G., Snijders, Marc P. L. M., Küsters-Vandevelde, Heidi V. N, Lucas, Peter J. F., Pijnenborg, Johanna M. A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/83394
Acceso en línea:https://doi.org/10.1371/journal.pmed.1003111
http://hdl.handle.net/10459.1/83394
Access Level:acceso abierto
Palabra clave:Endometrial cancer
Preoperative risk
Bayesian networks
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dc.title.none.fl_str_mv Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
title Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
spellingShingle Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
Reijnen, Casper
Endometrial cancer
Preoperative risk
Bayesian networks
title_short Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
title_full Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
title_fullStr Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
title_full_unstemmed Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
title_sort Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
dc.creator.none.fl_str_mv Reijnen, Casper
Gogou, Evangelia
Visser, Nicole C. M.
Engerud, Hilde
Ramjith, Jordache
van der Putten, Louis J. M.
van de Vijver, Koen
Santacana Espasa, Maria
Bronsert, Peter
Bulten, Johan
Hirschfeld, Marc
Colás, Eva
Gil-Moreno, Antonio
Reques, Armando
Mancebo, Gemma
Krakstad, Camilla
Trovik, Jone
Haldorsen, Ingfrid S.
Huvila, Jutta
Koskas, Martin
Weinberger, Vit
Bednaříková, Markéta
Hausnerova, Jitka
van der Wurff, Anneke A. M.
Matias-Guiu, Xavier
Amant, Frederic
Massuger, Leon F. A. G.
Snijders, Marc P. L. M.
Küsters-Vandevelde, Heidi V. N
Lucas, Peter J. F.
Pijnenborg, Johanna M. A.
author Reijnen, Casper
author_facet Reijnen, Casper
Gogou, Evangelia
Visser, Nicole C. M.
Engerud, Hilde
Ramjith, Jordache
van der Putten, Louis J. M.
van de Vijver, Koen
Santacana Espasa, Maria
Bronsert, Peter
Bulten, Johan
Hirschfeld, Marc
Colás, Eva
Gil-Moreno, Antonio
Reques, Armando
Mancebo, Gemma
Krakstad, Camilla
Trovik, Jone
Haldorsen, Ingfrid S.
Huvila, Jutta
Koskas, Martin
Weinberger, Vit
Bednaříková, Markéta
Hausnerova, Jitka
van der Wurff, Anneke A. M.
Matias-Guiu, Xavier
Amant, Frederic
Massuger, Leon F. A. G.
Snijders, Marc P. L. M.
Küsters-Vandevelde, Heidi V. N
Lucas, Peter J. F.
Pijnenborg, Johanna M. A.
author_role author
author2 Gogou, Evangelia
Visser, Nicole C. M.
Engerud, Hilde
Ramjith, Jordache
van der Putten, Louis J. M.
van de Vijver, Koen
Santacana Espasa, Maria
Bronsert, Peter
Bulten, Johan
Hirschfeld, Marc
Colás, Eva
Gil-Moreno, Antonio
Reques, Armando
Mancebo, Gemma
Krakstad, Camilla
Trovik, Jone
Haldorsen, Ingfrid S.
Huvila, Jutta
Koskas, Martin
Weinberger, Vit
Bednaříková, Markéta
Hausnerova, Jitka
van der Wurff, Anneke A. M.
Matias-Guiu, Xavier
Amant, Frederic
Massuger, Leon F. A. G.
Snijders, Marc P. L. M.
Küsters-Vandevelde, Heidi V. N
Lucas, Peter J. F.
Pijnenborg, Johanna M. A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Endometrial cancer
Preoperative risk
Bayesian networks
topic Endometrial cancer
Preoperative risk
Bayesian networks
description Background Bayesian networks (BNs) are machine-learning–based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node metastasis (LNM) is challenging in endometrial cancer, and although several biomarkers are related to LNM, none of them are incorporated in clinical practice. The aim of this study was to develop and externally validate a preoperative BN to predict LNM and outcome in endometrial cancer patients. Methods and findings Within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), we performed a retrospective multicenter cohort study including 763 patients, median age 65 years (interquartile range [IQR] 58–71), surgically treated for endometrial cancer between February 1995 and August 2013 at one of the 10 participating European hospitals. A BN was developed using score-based machine learning in addition to expert knowledge. Our main outcome measures were LNM and 5-year disease-specific survival (DSS). Preoperative clinical, histopathological, and molecular biomarkers were included in the network. External validation was performed using 2 prospective study cohorts: the Molecular Markers in Treatment in Endometrial Cancer (MoMaTEC) study cohort, including 446 Norwegian patients, median age 64 years (IQR 59–74), treated between May 2001 and 2010; and the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study cohort, including 384 Dutch patients, median age 66 years (IQR 60–73), treated between September 2011 and December 2013. A BN called ENDORISK (preoperative risk stratification in endometrial cancer) was developed including the following predictors: preoperative tumor grade; immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, and L1 cell adhesion molecule (L1CAM); cancer antigen 125 serum level; thrombocyte count; imaging results on lymphadenopathy; and cervical cytology. In the MoMaTEC cohort, the area under the curve (AUC) was 0.82 (95% confidence interval [CI] 0.76–0.88) for LNM and 0.82 (95% CI 0.77–0.87) for 5-year DSS. In the PIPENDO cohort, the AUC for 5-year DSS was 0.84 (95% CI 0.78–0.90). The network was well-calibrated. In the MoMaTEC cohort, 249 patients (55.8%) were classified with <5% risk of LNM, with a false-negative rate of 1.6%. A limitation of the study is the use of imputation to correct for missing predictor variables in the development cohort and the retrospective study design. Conclusions In this study, we illustrated how BNs can be used for individualizing clinical decision-making in oncology by incorporating easily accessible and multimodal biomarkers. The network shows the complex interactions underlying the carcinogenetic process of endometrial cancer by its graphical representation. A prospective feasibility study will be needed prior to implementation in the clinic.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1371/journal.pmed.1003111
http://hdl.handle.net/10459.1/83394
url https://doi.org/10.1371/journal.pmed.1003111
http://hdl.handle.net/10459.1/83394
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a https://doi.org/10.1371/journal.pmed.1003111
Plos Medicine, 2020, vol. 17, núm. 5, e1003111
dc.rights.none.fl_str_mv cc-by (c) Reijnen et al., 2020
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c) Reijnen et al., 2020
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation studyReijnen, CasperGogou, EvangeliaVisser, Nicole C. M.Engerud, HildeRamjith, Jordachevan der Putten, Louis J. M.van de Vijver, KoenSantacana Espasa, MariaBronsert, PeterBulten, JohanHirschfeld, MarcColás, EvaGil-Moreno, AntonioReques, ArmandoMancebo, GemmaKrakstad, CamillaTrovik, JoneHaldorsen, Ingfrid S.Huvila, JuttaKoskas, MartinWeinberger, VitBednaříková, MarkétaHausnerova, Jitkavan der Wurff, Anneke A. M.Matias-Guiu, XavierAmant, FredericMassuger, Leon F. A. G.Snijders, Marc P. L. M.Küsters-Vandevelde, Heidi V. NLucas, Peter J. F.Pijnenborg, Johanna M. A.Endometrial cancerPreoperative riskBayesian networksBackground Bayesian networks (BNs) are machine-learning–based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node metastasis (LNM) is challenging in endometrial cancer, and although several biomarkers are related to LNM, none of them are incorporated in clinical practice. The aim of this study was to develop and externally validate a preoperative BN to predict LNM and outcome in endometrial cancer patients. Methods and findings Within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), we performed a retrospective multicenter cohort study including 763 patients, median age 65 years (interquartile range [IQR] 58–71), surgically treated for endometrial cancer between February 1995 and August 2013 at one of the 10 participating European hospitals. A BN was developed using score-based machine learning in addition to expert knowledge. Our main outcome measures were LNM and 5-year disease-specific survival (DSS). Preoperative clinical, histopathological, and molecular biomarkers were included in the network. External validation was performed using 2 prospective study cohorts: the Molecular Markers in Treatment in Endometrial Cancer (MoMaTEC) study cohort, including 446 Norwegian patients, median age 64 years (IQR 59–74), treated between May 2001 and 2010; and the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study cohort, including 384 Dutch patients, median age 66 years (IQR 60–73), treated between September 2011 and December 2013. A BN called ENDORISK (preoperative risk stratification in endometrial cancer) was developed including the following predictors: preoperative tumor grade; immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, and L1 cell adhesion molecule (L1CAM); cancer antigen 125 serum level; thrombocyte count; imaging results on lymphadenopathy; and cervical cytology. In the MoMaTEC cohort, the area under the curve (AUC) was 0.82 (95% confidence interval [CI] 0.76–0.88) for LNM and 0.82 (95% CI 0.77–0.87) for 5-year DSS. In the PIPENDO cohort, the AUC for 5-year DSS was 0.84 (95% CI 0.78–0.90). The network was well-calibrated. In the MoMaTEC cohort, 249 patients (55.8%) were classified with <5% risk of LNM, with a false-negative rate of 1.6%. A limitation of the study is the use of imputation to correct for missing predictor variables in the development cohort and the retrospective study design. Conclusions In this study, we illustrated how BNs can be used for individualizing clinical decision-making in oncology by incorporating easily accessible and multimodal biomarkers. The network shows the complex interactions underlying the carcinogenetic process of endometrial cancer by its graphical representation. A prospective feasibility study will be needed prior to implementation in the clinic.This work was supported by the Dutch Cancer Society (JMAP, Grant: 10616/2016-2). The funder did not play any role in the design and conduct of the study; in the collection, management, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript.Public Library of Science2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1371/journal.pmed.1003111http://hdl.handle.net/10459.1/83394reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a https://doi.org/10.1371/journal.pmed.1003111Plos Medicine, 2020, vol. 17, núm. 5, e1003111cc-by (c) Reijnen et al., 2020info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:recercat.cat:10459.1/833942026-05-29T05:05:01Z
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