Effect of Whole-abdominal Irradiation on Penetration Depth of Doxorubicin in Normal Tissue After Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in a Post-mortem Swine Model

Background: This study was performed to evaluate the impact of whole-abdominal irradiation on local penetration of doxorubicin into the peritoneum and the abdominal organs in a post-mortem swine model. Materials and Methods: Doxorubicin was aerosolized into the abdominal cavity of swine at a pressure of 12 mmHg CO2 at room temperature (25 degrees). One swine was subjected to pressurized intraperitoneal aerosol chemotherapy (PIPAC) using Micropump (c) without irradiation; the second one received 2 Gy and the third one 7 Gy whole-abdominal irradiation, 15 min prior to PIPAC application. Samples of the peritoneal surface were extracted at different positions from within the abdominal cavity. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. Results: The depth of penetration of doxorubicin was found to be wide-ranging, between 17 mu m on the surface of the stomach and 348 mu m in the small intestine. The penetration depth into the small intestine was 348 mu m, 312 mu m and 265 mu m for PIPAC alone, PIPAC with 2 Gy irradiation and PIPAC with 7 Gy irradiation, respectively (p<0.05). The penetration into the liver was 64 mu m, 55 mu m and 40 mu m, respectively (p= 0.05). Conclusion: Irradiation was not found to increase the depth of doxorubicin penetration into normal tissue in the postmortem swine model. A reduction of doxorubicin penetration was observed after application of higher irradiation doses. Further studies are warranted to determine if irradiation can be used safely as chemopotentiating agent for patients with peritoneal metastases treated with PIPAC.