Modeling the mass transport in a tumor nodule during intraperitoneal chemotherapy

INTRODUCTION The intraperitoneal (IP) administration of chemotherapy is an alternative treatment to conventional chemotherapy for patients with peritoneal carcinomatosis. During IP therapy, the peritoneal membrane and embedded tumor nodules are brought into direct contact with the cytotoxic solution, aiming for a higher intratumor concentration. Currently, there is no widespread use of this promising therapy because of the limited drug penetration depth in the tumor tissue. Therefore, we present a mass transport model of a tumor nodule to analyze and optimize the drug penetration during IP therapy. METHODS To study the influence of different parameters governing the drug transport during IP chemotherapy, a 3D computational fluid dynamics (CFD) model was created representing a single tumor nodule (isotropic porous medium) and its simplified vascular network (Fig. 1). A parameter study was performed in which the drug diffusivity (9U+202210-9, 9U+202210-10 and 9U+202210-11 m2/s), tissue permeability (10-14 and 10-13 m2) and mass fraction of chemo at the tumor edge (10% and 20%) were varied. RESULTS The results of the parameter study showed that increasing the mass fraction (Fig. 2) leads to a large increase in the systemic concentration as measured at the vascular outlet (3U+202210-4 and 6U+202210-4 kmol/m3 after 1500 s for a mass fraction of 10% and 20%, respectively). However, a higher systemic concentration should ideally be avoided as it results in a higher systemic toxicity. Furthermore, the concentration along the black line in Fig. 1 (Fig. 2) shows only a very limited increase in penetration depth. Increasing the drug diffusivity resulted in an increase in both local and systemic concentrations Increasing the tissue permeability resulted in higher systemic concentrations of chemo and a minor increase in penetration depth. The response to permeability changes was found to be strongly non-linear and will be the subject of future work as this parameter is likely to be significantly different for healthy and tumor tissue. CONCLUSION The model is able to simulate the response of both local and systemic drug concentration profiles to changes in different drug and tissue properties during IP chemotherapy. Future work will focus on extending the model to more realistic configurations and validation.

Jaar van publicatie:2014

Toegankelijkheid:Closed