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Population modeling of tumor growth curves and the reduced Gompertz model improve prediction of the age of experimental tumors

hal.structure.identifierModélisation Mathématique pour l'Oncologie [MONC]
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
dc.contributor.authorVAGHI, Cristina
hal.structure.identifierSimulation and Modeling of Adaptive Response for Therapeutics in Cancer [SMARTc]
dc.contributor.authorRODALLEC, Anne
hal.structure.identifierSimulation and Modeling of Adaptive Response for Therapeutics in Cancer [SMARTc]
dc.contributor.authorFANCIULLINO, Raphaëlle
hal.structure.identifierSimulation and Modeling of Adaptive Response for Therapeutics in Cancer [SMARTc]
dc.contributor.authorCICCOLINI, Joseph
hal.structure.identifierIowa State University [ISU]
dc.contributor.authorMOCHEL, Jonathan
hal.structure.identifierRoswell Park Cancer Institute [Buffalo] [RPCI]
dc.contributor.authorMASTRI, Michalis
hal.structure.identifierModélisation Mathématique pour l'Oncologie [MONC]
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
dc.contributor.authorPOIGNARD, Clair
hal.structure.identifierRoswell Park Cancer Institute [Buffalo] [RPCI]
dc.contributor.authorEBOS, John
hal.structure.identifierModélisation Mathématique pour l'Oncologie [MONC]
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
dc.contributor.authorBENZEKRY, Sébastien
dc.date.accessioned2024-04-04T02:55:10Z
dc.date.available2024-04-04T02:55:10Z
dc.date.issued2020-02-25
dc.identifier.issn1553-734X
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/192339
dc.description.abstractEnTumor growth curves are classically modeled by means of ordinary differential equations. In analyzing the Gompertz model several studies have reported a striking correlation between the two parameters of the model, which could be used to reduce the dimensionality and improve predictive power. We analyzed tumor growth kinetics within the statistical framework of nonlinear mixed-effects (population approach). This allowed the simultaneous modeling of tumor dynamics and inter-animal variability. Experimental data comprised three animal models of breast and lung cancers, with 833 measurements in 94 animals. Candidate models of tumor growth included the exponential, logistic and Gompertz models. The exponential and-more notably-logistic models failed to describe the experimental data whereas the Gompertz model generated very good fits. The previously reported population-level correlation between the Gompertz parameters was further confirmed in our analysis (R2 > 0.92 in all groups). Combining this structural correlation with rigorous population parameter estimation, we propose a reduced Gompertz function consisting of a single individual parameter (and one population parameter). Leveraging the population approach using Bayesian inference, we estimated times of tumor initiation using three late measurement timepoints. The reduced Gompertz model was found to exhibit the best results, with drastic improvements when using Bayesian inference as compared to likelihood maximization alone, for both accuracy and precision. Specifically, mean accuracy (prediction error) was 12.2% versus 78% and mean precision (width of the 95% prediction interval) was 15.6 days versus 210 days, for the breast cancer cell line. These results demonstrate the superior predictive power of the reduced Gompertz model, especially when combined with Bayesian estimation. They offer possible clinical perspectives for personalized prediction of the age of a tumor from limited data at diagnosis. The code and data used in our analysis are publicly available at https://github.com/cristinavaghi/plumky.
dc.language.isoen
dc.publisherPublic Library of Science
dc.title.enPopulation modeling of tumor growth curves and the reduced Gompertz model improve prediction of the age of experimental tumors
dc.typeArticle de revue
dc.identifier.doi10.1371/journal.pcbi.1007178
dc.subject.halSciences du Vivant [q-bio]/Cancer
dc.subject.halSciences cognitives/Informatique
bordeaux.journalPLoS Computational Biology
bordeaux.pagee1007178
bordeaux.volume16
bordeaux.hal.laboratoriesInstitut de Mathématiques de Bordeaux (IMB) - UMR 5251*
bordeaux.issue2
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierinserm-02515955
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//inserm-02515955v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS%20Computational%20Biology&rft.date=2020-02-25&rft.volume=16&rft.issue=2&rft.spage=e1007178&rft.epage=e1007178&rft.eissn=1553-734X&rft.issn=1553-734X&rft.au=VAGHI,%20Cristina&RODALLEC,%20Anne&FANCIULLINO,%20Rapha%C3%ABlle&CICCOLINI,%20Joseph&MOCHEL,%20Jonathan&rft.genre=article


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