Effect of Layout and Shape to the Drug Delivery of Intratumoral Implant

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Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. In 2015, about 90.5 million people had cancer. About 14.1 million new cases occur a year.[1] It caused about 8.8 million deaths (15.7% of deaths).Abdominal cancer is a particular type of cancer that occurs when there is an uncontrolled growth of abnormal cells anywhere in the abdomen. It is one of the most pernicious types of cancer.[2] Since the abdomen consists of many organs, including the stomach, intestines, liver, gallbladder, and pancreas, abdominal cancer is more difficult to detect and treat. [3-5] Currently the most curative treatment option for abdominal cancers is surgical resection followed by adjuvant chemotherapy or radiation therapy to minimize the risk of recurrence [6]. Many cancers respond well to this treatment strategy, but many patients are not eligible for surgical resection due to a variety of reasons. For example, cancer of the liver is difficult to treat with resection because more than one liver lobe may be involved and the possibility of a coexisting liver condition (e.g., cirrhosis) [7]. Abdominal cancers, such as those of the pancreas and stomach, also have low resection success rates and poor overall patient survival [9]. Treatment of unresectable tumors has been supplemented in recent years by the development of minimally invasive interventions, such as laser, microwave, and radiofrequency (RF) ablation. [10] RF ablation in particular has shown improved efficacy, where approximately 80% of tumors cannot be surgically removed. However, despite its success, RF ablation is restricted by limited effective ablation volume that can be created with a single treatment as well as the risk of tumor recurrence around the boundary. [11-12] Biodegradable polymer implants, termed polymer millirods, have been designed to deliver chemotherapeutic agents to the RF treated region to kill residual tumor cells and prevent tumor recurrence. [8] These implants have been studied systematically in non-ablated and ablated liver tissues, and initial studies using doxorubicin-containing implants to treat tumors have indicated their potential benefit. Currently, the major challenge in effectively treating tumors with polymer millirods has been the limited drug penetration distance into the surrounding tissue. Although several changes to implant design have already been described, how these changes would affect local drug delivery and antitumor efficacy is still not known. In “Modeling doxorubicin transport to improve intratumoral drug delivery to RF ablated tumors”, the researchers built a mathematical model to provide an ideal strategy to optimize intratumoral drug delivery implants to supplement radiofrequency (RF) ablation for tumor treatment [8].They focused on the drug diffusion process in both a one-dimensional (1-D) simulation model and a more complex three-dimensional (3-D) simulation model. According to their experiment data and modeling analysis, they estimated the diffusion coefficient and drug elimination rate in ablated and non-ablated tumors. They found that RF ablation facilitates intratumoral drug delivery in tissue by reducing normal elimination processes and increasing diffusion. Also, they suggested that computational modeling approach has great advantages to design and rapidly prototype new implant treatment strategies. In "Polymer implants for intratumoral drug delivery and cancer therapy”, Weinberg et al. examined different designs of tumor implants to provide optimal drug release kinetics [7]. They examined the delivery goals for the implants and the methods to modulate local drug pharmacokinetics. They used three-dimensional (3-D) modeling to study the effect of using one central implant versus four peripheral implants on the drug diffusion process inside the tumor. The different layouts of the implants can maximize drug coverage of the tumor periphery, but also need to maintain a reasonable number of implants and total drug dose, which needs further exploration. These studies, we are going to create a more realistic model that replicates ablating a tumor in the liver and then delivering a chemotherapy drug, Doxorubicin, intratumorally. While previous research focused on the simplified spherical geometry, we constructed a more realistic three-dimensional (3-D) tumor simulation from a CT scan of the actual tumor. This will provide us with more accurate insight in our exploration of the optimal implant drug delivery.

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2020-05
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