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| Initial staging of cancer disease is critical in clinical oncology since it impacts on the
subsequent treatment strategies. In this respect, early detection of occult metastasis remaining
invisible upon imaging is an unmet medical need. Mathematical models describing metastatic
spreading could be attractive tools to better estimate the risk for a given tumor to spread when
clinical evidence is not available.
In this work, we have adapted a top-down model, constituted by a transport equation
describing metastatic growth and endowed with a boundary condition for metastatic emission.
Model predictions have been confronted with nonclinical experimental data. Nod Scid mice were
orthotopically xenografted with MDA-231 Luc+ breast cancer cells. Main tumor growth and
metastatic spreading and growth were monitored over up to six weeks by bioluminescence
tomography. A total of 166 observations on primary tumor size and 63 observations on metastatic
burden were obtained. For model building, a tailored computational approach permitted to use the
Monolix software, classically employed for Ordinary Differential Equations (ODE), for a Partial
Differential Equation (PDE) model. |
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