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

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Key points: 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.