REIJNEN, C., E. GOGOU, N. C. M. VISSER, H. ENGERUD, J. RAMJITH, L. J. M. VAN DER PUTTEN, K. V. DE VIJVER, M. SANTACANA, P. BRONSERT, J. BULTEN, M. HIRSCHFELD, E. COLAS, A. GIL-MORENO, A. REQUES, G. MANCEBO, C. KRAKSTAD, J. TROVIK, I. S. HALDORSEN, J. HUVILA, M. KOSKAS, Vít WEINBERGER, Markéta BEDNAŘÍKOVÁ, Jitka HAUSNEROVÁ, A. A. M. VAN DER WURFF, X. MATIAS-GUIU, F. AMANT, L. F. A. G. MASSUGER, M. P. L. M. SNIJDERS, H. V. N. KUSTERS-VANDEVELDE, P. J. F. LUCAS and J. M. A. PIJNENBORG. Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study. PLOS MEDICINE. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2020, vol. 17, No 5, p. 1-19. ISSN 1549-1277. Available from: https://dx.doi.org/10.1371/journal.pmed.1003111.
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Basic information
Original name Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study
Authors REIJNEN, C. (guarantor), E. GOGOU, N. C. M. VISSER, H. ENGERUD, J. RAMJITH, L. J. M. VAN DER PUTTEN, K. V. DE VIJVER, M. SANTACANA, P. BRONSERT, J. BULTEN, M. HIRSCHFELD, E. COLAS, A. GIL-MORENO, A. REQUES, G. MANCEBO, C. KRAKSTAD, J. TROVIK, I. S. HALDORSEN, J. HUVILA, M. KOSKAS, Vít WEINBERGER (203 Czech Republic, belonging to the institution), Markéta BEDNAŘÍKOVÁ (203 Czech Republic, belonging to the institution), Jitka HAUSNEROVÁ (203 Czech Republic, belonging to the institution), A. A. M. VAN DER WURFF, X. MATIAS-GUIU, F. AMANT, L. F. A. G. MASSUGER, M. P. L. M. SNIJDERS, H. V. N. KUSTERS-VANDEVELDE, P. J. F. LUCAS and J. M. A. PIJNENBORG.
Edition PLOS MEDICINE, SAN FRANCISCO, PUBLIC LIBRARY SCIENCE, 2020, 1549-1277.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30218 General and internal medicine
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 11.069
RIV identification code RIV/00216224:14110/20:00116535
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1371/journal.pmed.1003111
UT WoS 000558077100011
Keywords in English endometrial cancer; Bayesian network model
Tags 14110212, 14110230, 14110411, GPK, GPKonko, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 30/9/2020 13:34.
Abstract
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 (ENI-TEC), 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.
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