A 3D CFD model of the interstitial fluid pressure and drug distribution in heterogeneous tumor nodules during intraperitoneal chemotherapy

Drug Delivery

Margo Steuperaert¹  Charlotte Debbaut¹  Patrick Segers¹  Charlotte Carlier²  Wim Ceelen²  Olivier De Wever³  Benedicte Descamps⁴  Christian Vanhove⁴ 

[1] Biofluid, Tissue and Solid Mechanics for Medical Applications (bioMMeda), Department of Electronics and Information Systems, Ghent University, Ghent, Belgium;Departement of GI Surgery and Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Department of Human Structure and Repair, Ghent University, Ghent, Belgium;Infinity (iMinds-IBiTech-MEDISIP), Department of Electronics and Information Systems, Ghent University, Ghent, Belgiu;

关键词: Drug transport;    intraperitoneal chemotherapy;    interstitial fluid pressure;    DCE-MRI;    computational fluid dynamics;   

DOI  :  10.1080/10717544.2019.1588423

来源: publisher

【 摘 要 】

Although intraperitoneal chemotherapy (IPC) has evolved into an established treatment modality for patients with peritoneal metastasis (PM), drug penetration into tumor nodules remains limited. Drug transport during IPC is a complex process that depends on a large number of different parameters (e.g. drug, dose, tumor size, tumor pressure, tumor vascularization). Mathematical modeling allows for a better understanding of the processes that underlie drug transport and the relative importance of the parameters influencing it. In this work, we expanded our previously developed 3D Computational Fluid Dynamics (CFD) model of the drug mass transport in idealized tumor nodules during IP chemotherapy to include realistic tumor geometries and spatially varying vascular properties. DCE-MRI imaging made it possible to distinguish between tumorous tissues, healthy surrounding tissues and necrotic zones based on differences in the vascular properties. We found that the resulting interstitial pressure profiles within tumors were highly dependent on the irregular geometries and different zones. The tumor-specific cisplatin penetration depths ranged from 0.32 mm to 0.50 mm. In this work, we found that the positive relationship between tumor size and IFP does not longer hold in the presence of zones with different vascular properties, while we did observe a positive relationship between the percentage of viable tumor tissue and the maximal IFP. Our findings highlight the importance of incorporating both the irregular tumor geometries and different vascular zones in CFD models of IPC.

【 授权许可】

CC BY