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Published in: European Radiology 9/2014

01-09-2014 | Ultrasound

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

Authors: Jung Hoon Kim, Haeri Kim, Young Jae Kim, Jae Young Lee, Joon Koo Han, Byung-Ihn Choi

Published in: European Radiology | Issue 9/2014

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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.
Literature
1.
go back to reference Stathis A, Moore MJ (2010) Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 7:163–172PubMedCrossRef Stathis A, Moore MJ (2010) Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 7:163–172PubMedCrossRef
2.
go back to reference Hr B, Moore MJ, Andersen J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413 Hr B, Moore MJ, Andersen J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413
3.
go back to reference Visioli A, Rivens I, Ter Haar G et al (1999) Preliminary results of a phase I dose escalation clinical trial using focused ultrasound in the treatment of localised tumours. Eur J Ultrasound 9:11–18PubMedCrossRef Visioli A, Rivens I, Ter Haar G et al (1999) Preliminary results of a phase I dose escalation clinical trial using focused ultrasound in the treatment of localised tumours. Eur J Ultrasound 9:11–18PubMedCrossRef
4.
go back to reference Chen H, Li X, Wan M (2006) Spatial–temporal dynamics of cavitation bubble clouds in 1.2 MHz focused ultrasound field. Ultrason Sonochem 13:480–486PubMedCrossRef Chen H, Li X, Wan M (2006) Spatial–temporal dynamics of cavitation bubble clouds in 1.2 MHz focused ultrasound field. Ultrason Sonochem 13:480–486PubMedCrossRef
5.
go back to reference Coussios C, Farny C, Ter Haar G, Roy R (2007) Role of acoustic cavitation in the delivery and monitoring of cancer treatment by high-intensity focused ultrasound (HIFU). Int J Hyperth 23:105–120CrossRef Coussios C, Farny C, Ter Haar G, Roy R (2007) Role of acoustic cavitation in the delivery and monitoring of cancer treatment by high-intensity focused ultrasound (HIFU). Int J Hyperth 23:105–120CrossRef
6.
go back to reference Hancock HA, Smith LH, Cuesta J et al (2009) Investigations into Pulsed High-Intensity Focused Ultrasound–Enhanced Delivery: Preliminary Evidence for a Novel Mechanism. Ultrasound Med Biol 35:1722–1736PubMedCentralPubMedCrossRef Hancock HA, Smith LH, Cuesta J et al (2009) Investigations into Pulsed High-Intensity Focused Ultrasound–Enhanced Delivery: Preliminary Evidence for a Novel Mechanism. Ultrasound Med Biol 35:1722–1736PubMedCentralPubMedCrossRef
7.
go back to reference Kieran K, Hall TL, Parsons JE et al (2007) Refining histotripsy: defining the parameter space for the creation of nonthermal lesions with high intensity, pulsed focused ultrasound of the in vitro kidney. J Urol 178:672–676PubMedCrossRef Kieran K, Hall TL, Parsons JE et al (2007) Refining histotripsy: defining the parameter space for the creation of nonthermal lesions with high intensity, pulsed focused ultrasound of the in vitro kidney. J Urol 178:672–676PubMedCrossRef
8.
go back to reference Roberts WW, Hall TL, Ives K, Wolf JS Jr, Fowlkes JB, Cain CA (2006) Pulsed cavitational ultrasound: A noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney. J Urol 175:734–738PubMedCrossRef Roberts WW, Hall TL, Ives K, Wolf JS Jr, Fowlkes JB, Cain CA (2006) Pulsed cavitational ultrasound: A noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney. J Urol 175:734–738PubMedCrossRef
10.
go back to reference Lee JY, Choi BI, Ryu JK et al (2011) Concurrent chemotherapy and pulsed high-intensity focused ultrasound therapy for the treatment of unresectable pancreatic cancer: initial experiences. Korean J Radiol 12:176–186PubMedCentralPubMedCrossRef Lee JY, Choi BI, Ryu JK et al (2011) Concurrent chemotherapy and pulsed high-intensity focused ultrasound therapy for the treatment of unresectable pancreatic cancer: initial experiences. Korean J Radiol 12:176–186PubMedCentralPubMedCrossRef
11.
go back to reference Wang K, Chen Z, Meng Z et al (2011) Analgesic effect of high intensity focused ultrasound therapy for unresectable pancreatic cancer. Int J Hyperth 27:101–107CrossRef Wang K, Chen Z, Meng Z et al (2011) Analgesic effect of high intensity focused ultrasound therapy for unresectable pancreatic cancer. Int J Hyperth 27:101–107CrossRef
12.
go back to reference R-s W, Liu L-x G, Y-h LQ-f, R-h G, Y-q S (2010) The effect of endostatin and gemcitabine combined with HIFU on the animal xenograft model of human pancreatic cancer. Biomed Pharmacother 64:309–312CrossRef R-s W, Liu L-x G, Y-h LQ-f, R-h G, Y-q S (2010) The effect of endostatin and gemcitabine combined with HIFU on the animal xenograft model of human pancreatic cancer. Biomed Pharmacother 64:309–312CrossRef
13.
go back to reference Wu F, Wang Z-B, Zhu H et al (2005) Feasibility of US-guided High-Intensity Focused Ultrasound Treatment in Patients with Advanced Pancreatic Cancer: Initial Experience1. Radiology 236:1034–1040PubMedCrossRef Wu F, Wang Z-B, Zhu H et al (2005) Feasibility of US-guided High-Intensity Focused Ultrasound Treatment in Patients with Advanced Pancreatic Cancer: Initial Experience1. Radiology 236:1034–1040PubMedCrossRef
14.
go back to reference Hwang M, Niermann KJ, Lyshchik A, Fleischer AC (2009) Sonographic assessment of tumor response: from in vivo models to clinical applications. Ultrasound Quart 25:175–183CrossRef Hwang M, Niermann KJ, Lyshchik A, Fleischer AC (2009) Sonographic assessment of tumor response: from in vivo models to clinical applications. Ultrasound Quart 25:175–183CrossRef
15.
go back to reference Lassau N, Koscielny S, Albiges L et al (2010) Metastatic renal cell carcinoma treated with sunitinib: early evaluation of treatment response using dynamic contrast-enhanced ultrasonography. Clin Cancer Res 16:1216–1225PubMedCrossRef Lassau N, Koscielny S, Albiges L et al (2010) Metastatic renal cell carcinoma treated with sunitinib: early evaluation of treatment response using dynamic contrast-enhanced ultrasonography. Clin Cancer Res 16:1216–1225PubMedCrossRef
16.
go back to reference Lassau N, Koscielny S, Chami L et al (2011) Advanced hepatocellular carcinoma: early evaluation of response to bevacizumab therapy at dynamic contrast-enhanced US with quantification—preliminary results. Radiology 258:291–300PubMedCrossRef Lassau N, Koscielny S, Chami L et al (2011) Advanced hepatocellular carcinoma: early evaluation of response to bevacizumab therapy at dynamic contrast-enhanced US with quantification—preliminary results. Radiology 258:291–300PubMedCrossRef
17.
go back to reference Sirsi SR, Flexman ML, Vlachos F et al (2012) Contrast ultrasound imaging for identification of early responder tumor models to anti-angiogenic therapy. Ultrasound Med Biol 38:1019–1029PubMedCentralPubMedCrossRef Sirsi SR, Flexman ML, Vlachos F et al (2012) Contrast ultrasound imaging for identification of early responder tumor models to anti-angiogenic therapy. Ultrasound Med Biol 38:1019–1029PubMedCentralPubMedCrossRef
18.
go back to reference Nishida M, Koito K, Hirokawa N, Hori M, Satoh T, Hareyama M (2009) Does contrast-enhanced ultrasound reveal tumor angiogenesis in pancreatic ductal carcinoma? A prospective study. Ultrasound Med Biol 35:175–185PubMedCrossRef Nishida M, Koito K, Hirokawa N, Hori M, Satoh T, Hareyama M (2009) Does contrast-enhanced ultrasound reveal tumor angiogenesis in pancreatic ductal carcinoma? A prospective study. Ultrasound Med Biol 35:175–185PubMedCrossRef
19.
go back to reference Zhao H, Yang G, Wang D et al (2010) Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer. Anti-Cancer Drugs 21:447–452PubMedCrossRef Zhao H, Yang G, Wang D et al (2010) Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer. Anti-Cancer Drugs 21:447–452PubMedCrossRef
20.
go back to reference Lee ES, Lee JY, Kim H et al (2013) Pulsed High-Intensity Focused Ultrasound Enhances Apoptosis of Pancreatic Cancer Xenograft with Gemcitabine. Ultrasound in medicine & biology Lee ES, Lee JY, Kim H et al (2013) Pulsed High-Intensity Focused Ultrasound Enhances Apoptosis of Pancreatic Cancer Xenograft with Gemcitabine. Ultrasound in medicine & biology
21.
go back to reference Greis C (2011) Quantitative evaluation of microvascular blood flow by contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc 49:137–149PubMed Greis C (2011) Quantitative evaluation of microvascular blood flow by contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc 49:137–149PubMed
Metadata
Title
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
Authors
Jung Hoon Kim
Haeri Kim
Young Jae Kim
Jae Young Lee
Joon Koo Han
Byung-Ihn Choi
Publication date
01-09-2014
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 9/2014
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-014-3260-4

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