Feasibility of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in a Rabbit Model of Peritoneal Metastases: PIPALIM Project.

Abstract

BACKGROUND: Animal models are essential for testing new pressurized intraperitoneal aerosol chemotherapy (PIPAC) protocols; however, no immunocompetent animal model of peritoneal surface malignancies (PSMs) treated with PIPAC has been established. This study evaluated the feasibility, safety, and oncological efficacy of PIPAC in a rabbit PSM model. METHODS: The study was conducted in two phases: (1) Feasibility Assessment: Three healthy rabbits underwent three consecutive PIPAC procedures (saline) at weekly intervals. The rabbits' well-being, morbidity, mortality, and histological changes were monitored. (2) Treatment Phase: Rabbits with PSM were treated with PIPAC using oxaliplatin, cisplatin-doxorubicin, or saline. Parameters such as animal well-being, ascites volume, morbidity, Peritoneal Cancer Index (PCI), histological response (Peritoneal Regression Grading Score [PRGS]), tumor cell proliferation/apoptosis, and circulating tumor DNA (ctDNA) levels were assessed. RESULTS: PIPAC was feasible and safe, with no increased morbidity or mortality. PIPAC demonstrated antitumor efficacy with lower PCI (control 21.6 vs. oxaliplatin 9.2 vs. cisplatin-doxorubicin 10.2; p&#xa0;<&#xa0;0.001), improved histological response (PRGS: control 3.38 vs. oxaliplatin 1.95 vs. cisplatin-doxorubicin 1.85; p&#xa0;=&#xa0;0.01), and reduced tumor cell proliferation (control 5.3% vs. oxaliplatin 0.82% vs. cisplatin-doxorubicin 0.62%; p&#xa0;<&#xa0;0.0001). ctDNA levels showed promise for monitoring treatment response, warranting further investigation. CONCLUSION: This study confirms the feasibility and effectiveness of PIPAC with oxaliplatin or cisplatin-doxorubicin in rabbits with PSM. The model provides a foundation for future research on PIPAC protocols and related treatments.