4:12 PM Abstract No. 198 Transarterial embolization of liver cancer in a transgenic pig model

Abstract

To develop a porcine model of liver cancer, which could be used to test new locoregional therapies. Liver tumors were induced in 14 Oncopigs (transgenic pigs with Cre-inducible p53 and Kras mutations) by using an adenovirus carrying the Cre-recombinase gene. The resulting tumors (n = 50) were characterized on multiphase contrast-enhanced CT, angiography, and necropsy. Transarterial embolization was performed using 40-120 micron or 100-300 micron Embospheres. Response to embolization was evaluated by mRECIST, and on pathology. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy. Liver tumors developed at 50 of 58 sites (86%) that were inoculated. Average tumor size was 2.1 cm at 1 week. Histopathology revealed an invasive malignant neoplasm, with metastases to lymph nodes and peritoneum in some cases. H&E staining and immunohistochemistry showed poorly differentiated or undifferentiated tumors of undetermined origin, but features suggesting a biliary epithelial origin were seen in some cases. Neoplastic cells were accompanied by a major inflammatory component. 2 of 14 pigs only had inflammatory nodules without evidence of neoplasia. On multiphase CT, all tumors had a hypovascular center, and 18 of 50 (36%) had a hypervascular rim. After transarterial embolization, non-contrast CT showed retained contrast in the tumors. Follow-up contrast-enhanced scan showed a complete radiographic response in 3 of 3 pigs treated using 40-120 micron Embospheres, and 2 of 3 pigs treated using 100-300 micron Embospheres. One pig treated with 40-120 micron Embospheres developed postembolization syndrome (vomiting) requiring euthanasia. One pig treated with 100-300 micron Embospheres died during sedation for terminal imaging, and was found to have a large right pleural effusion, liver infarct, and progressive extrahepatic disease. Liver tumors can be induced in a transgenic pig, and can be successfully treated using bland embolization. This new model system could be used to develop the next generation of arterially directed therapies for primary or secondary liver cancer.