Isolated effects of regional hyperthermic perfusion on the development of peritoneal metastasis and overall survival in rats with transplanted high-grade ovarian carcinoma

Abstract

Aim:  To construct a perfusion circuit for experimental open hyperthermic intraperitoneal perfusion (HIPEP) and to evaluate the antitumor effects of regional hyperthermia in a model of advanced syngeneic high-grade ovarian carcinoma in vivo.

Method: 24 mature female Wistar rats underwent intraperitoneal transplantation of ascitic ovarian tumor 1×10⁷ cells per rat. 48 hours after transplantation the animals were randomized into two groups: I. NIPEP group (12 rats) – normothermic intraperitoneal perfusion (NIPEP) with normal saline at room temperature during 45 minutes; II. HIPEP group (12 rats) – open hyperthermic intraperitoneal perfusion (HIPEP) with normal saline (40.5-41.5 ℃) during 45 minutes. Endpoints included overall survival (OS), the total peritoneal cancer index (PCI), ascites weight and the grade of ascites hemorrhage.

Results: In both groups all animals survived the procedure, in the HIPEP group one rat died due to infectious complications on day 32. Compared with NIPEP group HIPEP with normal saline significantly increased the median OS from 19 to 39 days (log-rank test, P=0.0013), reducing the risk of death by 68% (HR=0.32; 95% CI 0.13-0.82). The open HIPEP without a cytostatic was associated with significantly lower total PCI (14 vs 5 points, P=0.0155). In the HIPEP group 3 of 12 animals had intrathoracic tumor spread with malignant pleural effusion without signs of peritoneal carcinomatosis and ascites.

Conclusion: The transplanted syngeneic tumor is a valid model that allows to quantitatively assess antitumor activity of intraperitoneal perfusion therapy. Our preclinical data confirmed the role of regional hyperthermia in the treatment of peritoneal carcinomatosis in ovarian tumors.