Image-Based Modeling of Drug Delivery during Intraperitoneal Chemotherapy in a Heterogeneous Tumor Nodule

SIMPLE SUMMARY: Intraperitoneal (IP) chemotherapy is a treatment for cancers in the abdomen, delivering anti-cancer drugs directly into the peritoneal cavity. While this method has shown promising outcomes, limited drug penetration into tumors remains a challenge due to their unique pathophysiology. Our study aims to investigate drug delivery during IP chemotherapy using a mathematical model. We incorporated a real tumor image into our model to understand how tumor vessels and their distribution affect drug delivery. Our model allowed us to analyze the spatiotemporal distribution of drug concentration in the tumor. We also quantitatively evaluated treatment efficacy by examining drug availability in the tumor, drug penetration depth, and the fraction of killed cells during the treatment. Our findings revealed that each tumor’s specific vascular network can impact drug delivery during IP chemotherapy. Our model provides valuable insights into the challenges of IP chemotherapy and holds promise for applications in personalized medicine. ABSTRACT: Intraperitoneal (IP) chemotherapy is a promising treatment approach for patients diagnosed with peritoneal carcinomatosis, allowing the direct delivery of therapeutic agents to the tumor site within the abdominal cavity. Nevertheless, limited drug penetration into the tumor remains a primary drawback of this method. The process of delivering drugs to the tumor entails numerous complications, primarily stemming from the specific pathophysiology of the tumor. Investigating drug delivery during IP chemotherapy and studying the parameters affecting it are challenging due to the limitations of experimental studies. In contrast, mathematical modeling, with its capabilities such as enabling single-parameter studies, and cost and time efficiency, emerges as a potent tool for this purpose. In this study, we developed a numerical model to investigate IP chemotherapy by incorporating an actual image of a tumor with heterogeneous vasculature. The tumor’s geometry is reconstructed using image processing techniques. The model also incorporates drug binding and uptake by cancer cells. After 60 min of IP treatment with Doxorubicin, the area under the curve (AUC) of the average free drug concentration versus time curve, serving as an indicator of drug availability to the tumor, reached 295.18 mol·m(−3)·s(−1). Additionally, the half-width parameter W(1/2), which reflects drug penetration into the tumor, ranged from 0.11 to 0.14 mm. Furthermore, the treatment resulted in a fraction of killed cells reaching 20.4% by the end of the procedure. Analyzing the spatial distribution of interstitial fluid velocity, pressure, and drug concentration in the tumor revealed that the heterogeneous distribution of tumor vasculature influences the drug delivery process. Our findings underscore the significance of considering the specific vascular network of a tumor when modeling intraperitoneal chemotherapy. The proposed methodology holds promise for application in patient-specific studies.