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Mathematical Modeling of Drug Transport during Intraperitoneal Chemotherapy

(2016)
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Abstract
AIM: Patients with peritoneal carcinomatosis suffer from a widespread metastatic growth of tumor nodules in the peritoneal cavity. Intraperitoneal (IP) chemotherapy is an alternative treatment, that allows for higher intratumor concentrations of the cytotoxic agent and less side effects compared to conventional intravenous administration. Although IP chemotherapy is a promising technique, its clinical application is still limited due to the poor drug penetration (typically a few millimeters) in the tumor tissue. It is thus essential to better understand the drug transport during IP chemotherapy. To this end, we developed a computational fluid dynamics (CFD) model that allows for testing the influence of therapy-related parameters. METHODS & RESULTS: A 3D CFD model of a tumor nodule was created in Comsol (COMSOL, Inc., Burlington, USA) to describe the drug transport during IP chemotherapy. The model includes the convective, diffusive and reactive drug transport in different tumor geometries with a necrotic core (e.g. a spherical baseline model with radius r = 1 cm and rnecrotic = 5 mm; Fig. 1a). Tumor tissue is modeled as a rigid porous medium using Darcy’s Law (permeability of 3.10 E-17 m2 for baseline model). Incompressible interstitial fluid flow is modeled by the steady-state continuity equation in which the constitutive relation for the fluid gain from the vasculature is based on Starling’s hypothesis and lymphatic loss is neglected. The time-dependent drug concentration is calculated using mass conservation accounting for convective-diffusive transport and including the drug loss by cell uptake and vascular uptake. Boundary conditions include a zero pressure and fixed concentration at the outer tumor edge (c = 0.0125 mol/m3 for baseline model). The baseline model was subsequently adapted to perform a parameter study of therapy-related parameters (i.e. different types of drugs, tissue permeability, presence of necrotic core, vascular properties etc.) on the drug penetration. Next, the resulting concentration profiles were analyzed to distinguish the general trend for each of the parameters (e.g. better drug penetration for drugs with a higher diffusivity). CONCLUSIONS: The model is able to predict drug penetration depth and local drug concentrations for different sets of IP chemotherapy-related parameters, which may lead to the optimization of drug transport during IP chemotherapy.

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Citation

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MLA
Steuperaert, Margo, Giuseppe Falve D’Urso Labate, Charlotte Debbaut, et al. “Mathematical Modeling of Drug Transport During Intraperitoneal Chemotherapy.” 2016. Print.
APA
Steuperaert, M., Falve D’Urso Labate, G., Debbaut, C., Ceelen, W., & Segers, P. (2016). Mathematical Modeling of Drug Transport during Intraperitoneal Chemotherapy. Presented at the ECCOMAS.
Chicago author-date
Steuperaert, Margo, Giuseppe Falve D’Urso Labate, Charlotte Debbaut, Wim Ceelen, and Patrick Segers. 2016. “Mathematical Modeling of Drug Transport During Intraperitoneal Chemotherapy.” In .
Chicago author-date (all authors)
Steuperaert, Margo, Giuseppe Falve D’Urso Labate, Charlotte Debbaut, Wim Ceelen, and Patrick Segers. 2016. “Mathematical Modeling of Drug Transport During Intraperitoneal Chemotherapy.” In .
Vancouver
1.
Steuperaert M, Falve D’Urso Labate G, Debbaut C, Ceelen W, Segers P. Mathematical Modeling of Drug Transport during Intraperitoneal Chemotherapy. 2016.
IEEE
[1]
M. Steuperaert, G. Falve D’Urso Labate, C. Debbaut, W. Ceelen, and P. Segers, “Mathematical Modeling of Drug Transport during Intraperitoneal Chemotherapy,” presented at the ECCOMAS, CRETE, 2016.
@inproceedings{8134582,
  abstract     = {AIM: Patients with peritoneal carcinomatosis suffer from a widespread metastatic growth of tumor nodules in the peritoneal cavity. Intraperitoneal (IP) chemotherapy is an alternative treatment, that allows for higher intratumor concentrations of the cytotoxic agent and less side effects compared to conventional intravenous administration. Although IP chemotherapy is a promising technique, its clinical application is still limited due to the poor drug penetration (typically a few millimeters) in the tumor tissue. It is thus essential to better understand the drug transport during IP chemotherapy. To this end, we developed a computational fluid dynamics (CFD) model that allows for testing the influence of therapy-related parameters.
METHODS & RESULTS: A  3D  CFD model of a tumor nodule was created in Comsol (COMSOL, Inc., Burlington, USA) to describe the drug transport during IP chemotherapy. The model includes the convective, diffusive and reactive drug transport in different tumor geometries with a necrotic core (e.g. a spherical baseline model with radius r = 1 cm and rnecrotic = 5 mm; Fig. 1a).
Tumor tissue is modeled as a rigid porous medium using Darcy’s Law (permeability of 3.10 E-17 m2 for baseline model). Incompressible interstitial fluid flow is modeled by the steady-state continuity equation in which the constitutive relation for the fluid gain from the vasculature is based on Starling’s hypothesis and lymphatic loss is neglected. The time-dependent drug concentration is calculated using mass conservation accounting for convective-diffusive transport and including the drug loss by cell uptake and vascular uptake. Boundary conditions include a zero pressure and fixed concentration at the outer tumor edge (c = 0.0125 mol/m3 for baseline model).
The baseline model was subsequently adapted to perform a parameter study of therapy-related parameters (i.e. different types of drugs, tissue permeability, presence of necrotic core, vascular properties etc.) on the drug penetration. Next, the resulting concentration profiles were analyzed to distinguish the general trend for each of the parameters (e.g. better drug penetration for drugs with a higher diffusivity).
CONCLUSIONS: The model is able to predict drug penetration depth and local drug concentrations for different sets of IP chemotherapy-related parameters, which may lead to the optimization of drug transport during IP chemotherapy.},
  author       = {Steuperaert, Margo and Falve D'Urso Labate, Giuseppe and Debbaut, Charlotte and Ceelen, Wim and Segers, Patrick},
  language     = {eng},
  location     = {CRETE},
  title        = {Mathematical Modeling of Drug Transport during Intraperitoneal Chemotherapy},
  year         = {2016},
}