Abstract 2825: Experimental hyperthermic intraperitoneal chemotherapy in mice: Establishment of a novel ovarian cancer xenograft model

Abstract

Abstract Introduction: The peritoneum is a common metastatic site for several abdominal cancers, including ovarian and colorectal cancer. Peritoneal metastasis is associated with poor prognosis and poor response to therapy. A potentially curative treatment is cytoreductive surgery (CRS) to remove all visible tumor tissue, followed by perfusion with hyperthermic intraperitoneal chemotherapy (HIPEC) to eliminate small residual tumors and free-floating tumor cells. Hyperthermia can enhance the cytotoxic effect of the drug, inhibit DNA repair and activate the immune system. At the current time, there is no standardized protocol for performing HIPEC, and there is a large variation regarding key parameters, such as choice of drug, drug concentration, treatment duration, carrier solution, volume and temperature. The impact of these parameters is unknown, and in vivo models can be a helpful tool to better understand some of these parameters to improve this treatment strategy. Methods: HIPEC was established in a murine xenograft model of ovarian cancer to evaluate the response to intraperitoneal perfusion of cisplatin and mitomycin C for 30 min at 41.5°C (HIPEC) and 37°C (NIPEC) compared to no treatment or intraperitoneal perfusion with saline at 41.5°C. The luciferase transfected B76 ovarian cancer cell line was injected intraperitoneally and treatment was performed on day 4 when the tumors were < 2 mm. Treatment efficacy was assessed by weekly luminescence measurement, tumor weight at an early time point (day 17), and overall survival. Results: Intraperitoneal perfusion with cisplatin or mitomycin C significantly inhibited tumor growth as assessed by luminescence, tumor weight on day 17, as well as increased overall survival of the mice compared to control treatment from 25-27 days to 36 days for cisplatin and 37 days for mitomycin C. No significant differences in tumor growth or survival were observed by the addition of hyperthermia. However, a slight reduction of tumor weight at day 17 was observed in the HIPEC groups. Conclusion: We have established a functional closed HIPEC model in mice bearing peritoneal metastases from the B76 ovarian cancer cell line which accurately mimics many features of the procedure in patients. Intraperitoneal perfusion of both cisplatin and mitomycin C efficaciously inhibited tumor growth and improved overall survival of the mice. Addition of hyperthermia caused an additional modest, temporary growth inhibition which did not translate into improved long-term outcome. Citation Format: Karianne Giller Fleten, Yvonne Andersson, Emil Løvstakken, Theodor M. Herud, Stein Waagene, Kjersti Flatmark. Experimental hyperthermic intraperitoneal chemotherapy in mice: Establishment of a novel ovarian cancer xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2825.