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 W1/2, 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.
腹腔内化疗是治疗腹膜癌患者的一种前景广阔的治疗方法，能够将治疗药物直接递送至腹腔内的肿瘤部位。然而，药物在肿瘤组织中的渗透能力有限仍是该方法的主要缺陷。药物递送至肿瘤的过程涉及诸多复杂因素，主要源于肿瘤特有的病理生理学特性。由于实验研究的局限性，探究腹腔内化疗中的药物递送过程及其影响因素具有挑战性。相比之下，数学模型因其能够进行单参数研究、且具有成本和时间效益等特点，成为解决这一问题的有力工具。本研究通过整合具有异质性血管系统的真实肿瘤图像，建立了一个数值模型以研究腹腔内化疗。利用图像处理技术重建了肿瘤的几何结构，该模型同时考虑了药物与癌细胞的结合及摄取过程。在使用阿霉素进行腹腔内治疗60分钟后，作为肿瘤药物可用性指标的平均游离药物浓度-时间曲线下面积达到295.18 mol·m⁻³·s⁻¹。此外，反映药物向肿瘤渗透能力的半宽度参数W₁/₂介于0.11至0.14 mm之间。治疗结束时，被杀灭细胞比例达到20.4%。通过分析肿瘤组织间液流速、压力及药物浓度的空间分布，发现肿瘤血管系统的异质性分布会影响药物递送过程。我们的研究结果强调了在建立腹腔内化疗模型时考虑肿瘤特异性血管网络的重要性。所提出的方法在个体化医疗研究中具有应用潜力。
肿瘤(癌症)患者之家