Dynamic contrast-enhanced ultrasonographic (DCE-US) assessment of the early response after combined gemcitabine and HIFU with low-power treatment for the mouse xenograft model of human pancreatic cancer.

Abstract

To assess therapeutic efficacy of gemcitabine and HIFU for a mouse model of pancreatic cancer, and the role of DCE-US for predicting early treatment response compared with pathology. In 48 PANC-1- nude mice (G1, HIFU_higher power [n = 14]; G2, gemcitabine [n = 12]; G3, combined gemcitabine and HIFU_low power [n = 12]; and G4, control [n = 10]), pulsed HIFU or gemcitabine therapy was used. DCE-US was performed 1 day before and after first treatment. Seven DCE-US perfusion parameters were obtained. Therapeutic efficacy was estimated using necrotic fraction and apoptosis. Correlation between tumour size and US perfusion parameters was analysed. Pathology results showed that combined gemcitabine and HIFU using low-power treatment had a more effective response than other treatments, including in the control group, i.e. necrotic fraction: 40.5 ± 4.9 vs. 16.9 ± 8.0, p = 0.000 and apoptosis: 44.3 ± 29.4 vs. 7.9 ± 4.9, p = 0.002. In this group, US perfusion parameters, including peak intensity (22.6 ± 22.6 vs. 9.6 ± 6.3, p = 0.002), AUC (961.8 ± 96.9 vs. 884.4 ± 91.4, p = 0.000), and AUCout (799.9 ± 75.6 vs. 747.1 ± 77.9, p = 0.000), had significantly decreased 1 day following first treatment (p < 0.05). In addition, peak intensity, AUC, and AUCout showed a tendency to decrease in treated groups. Alternatively, peak intensity, AUC, and AUCout showed a tendency to increase in control group. Gemcitabine and HIFU were more effective and safer than other treatments. US perfusion parameters were useful for predicting early therapeutic response 1 day following treatment. Recently, treatment of pancreatic cancer has changed based on a multidisciplinary approach. Combined gemcitabine_HIFU demonstrated more effective therapeutic response than other treatments. DCE-US is useful for predicting early therapeutic response 1 day after treatment. In the combined group, PI, AUC, and AUC (out) decreased 1 day after treatment.