title: Spatial modelling of tumour drug resistance: the case of GIST liver metastases.
abstract: This work is devoted to modelling gastrointestinal stromal tumour metastases to the liver, their growth and resistance to therapies. More precisely, resistance to two standard treatments based on tyrosine kinase inhibitors (imatinib and sunitinib) is observed clinically. Using observations from medical images (CT scans), we build a spatial model consisting in a set of non-linear partial differential equations. After calibration of its parameters with clinical data, this model reproduces qualitatively and quantitatively the spatial tumour evolution of one specific patient. Important features of the growth such as the appearance of spatial heterogeneities and the therapeutical failures may be explained by our model. We then investigate numerically the possibility of optimizing the treatment in terms of progression-free survival time and minimum tumour size reachable by varying the dose of the first treatment. We find that according to our model, the progression-free survival time reaches a plateau with respect to this dose. We also demonstrate numerically that the spatial structure of the tumour may provide much more insights on the cancer cell activities than the standard RECIST criteria, which only consists in the measurement of the tumour diameter. Finally, we discuss on the non-predictivity of the model using only CT scans, in the sense that the early behaviour of the lesion is not sufficient to predict the response to the treatment.
authors.affiliation: Univ. Bordeaux, IMB, UMR 5251 and INRIA Bordeaux-Sud-Ouest, F-33400, Talence, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lefebvre
authors.affiliation: Univ. Bordeaux, IMB, UMR 5251, F-33400, Talence, France and Service d'imagerie diagnostique et interventionnelle de l'adulte, Hopital Pellegrin, CHU de Bordeaux, Bordeaux, France.
authors.forename: François
authors.initials: F
authors.lastname: Cornelis
authors.affiliation: Group of Applied Mathematics (GMA) and Group of Tumour Angiogenesis (GIANT), Basic Sciences Department, Faculty of Sciences, Universidad del Bio-Bio, Campus Fernando May, Chillaan, Chile and Centre for Biotechnology and Bioengineering, University of Chile, Beauchef 850, Santiago, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Cumsille
authors.affiliation: Bordeaux INP, Univ. Bordeaux, IMB, UMR 5251 and INRIA Bordeaux-Sud-Ouest, F-33400, Talence, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Colin
authors.affiliation: INRIA Bordeaux-Sud-Ouest and CNRS, IMB, UMR 5251, F-33400, Talence, France.
authors.forename: Clair
authors.initials: C
authors.lastname: Poignard
authors.affiliation: INRIA Bordeaux-Sud-Ouest and CNRS, IMB, UMR 5251, F-33400, Talence, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Saut
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D019008:Drug Resistance, Neoplasm; D005770:Gastrointestinal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D055641:Mathematical Concepts; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D017711:Nonlinear Dynamics; D014057:Tomography, X-Ray Computed
keywords: cancer; drug resistance; partial differential equations; tumour growth modelling; tumour heterogeneity