The growth rate of in situ-induced hepatic lesions in an Oncopig large animal model is quantitatively assessed. Oncopigs (n = 9) received baseline triple-phase CT scans prior to lesion induction. Lesions were subsequently induced by delivering the Ad-Cre vector to four locations in the liver. Triple-phase CT scans were obtained weekly to track the growth of the lesions. Animals were sacrificed at 14, 21, or 28 days (n = 3 in each group). The overall success rate of lesion generation was ~78%. Histopathology sections consistently revealed lesions that were highly inflammatory and consisted of a large leukocyte population without clear evidence of carcinomas. Lesions presented within imaging as hypovascular, low attenuating masses with slight contrast enhancement around the margins but little to no enhancement within the lesions themselves. The observed lesions were manually segmented on the venous phase image. Segmentation volumes were fitted to a logistic growth and decay model. Several lesions observed at earlier time points in the 28-day group had fully regressed by the time of the necropsy. The overall trend of rapid growth for the first 21 days, with spontaneous regression of the lesions being observed from day 21 to 28, suggests that the optimal window for experimental studies may be from days 14 to 21. The data and mathematical models generated from this study may be used for future computational models; however, the current model presented has moderate clinical relevance because many induced tumors resolved spontaneously within a few weeks. Awareness and careful consideration of the modest relevance and limitations of the model are advisable for each specific use case.
Keywords: hepatocellular carcinoma; image segmentation; large animal model; mathematical modeling.