Biophysical Model of Interstitial Fluid Pressure in Cervical Tumors

Abstract

Interstitial fluid pressure (IFP) was measured prior to treatment in patients with cervix cancer at Toronto’s Princess Margaret Hospital as part of a prospective clinical study. The results showed that there was a strong correlation between elevated IFP and patient survival, regardless of other prognostic factors such as patient age, stage or lymphatic involvement. With a view to understanding this important correlation, we developed a biophysical model of interstitial fluid flow in cancer tissue based on Darcy’s law (a mathematical law developed originally to describe water flow through porous media). Flow through the pressure-recording device was also modeled.  The result was a mathematical expression showing how measured IFP changes as a function of time, after insertion of the measurement needle into the tumor.  By analyzing 152 pressure-time curves observed in this manner, we were able to show (i) that the time constant governing the rise of measured pressure has no correlation with the steady state IFP; and (ii) that the steady IFP does not depend in any significant way on the cellular morphology or the hydraulic conductivity of the interstitium, but is more dependent on the regional vascular pressure. Our findings suggest that the source of the observed elevation of IFP in cancer patients relates to the nature and distribution of tumor vasculature, rather than to properties of cancer cells themselves.