High-Intensity Focused Ultrasound Ablation of Pancreatic Cancer

Abstract

Pancreatic cancer is one of the leading causes of cancer deaths, and many patients, with advanced disease, suffer from severe pain that can heavily affect their quality of life. In patients with advanced disease, an eminent role is played by percutaneous techniques, which cause tumor necrosis with a minimally invasive approach. High-intensity focused ultrasound (HIFU) is a relatively recent noninvasive technique that allows ablation of different solid tumors including uterine fibroids, and hepatic, renal, and pancreatic tumors. HIFU technology is based on external emission of an ultrasound beam, which has larger amplitudes than the regular diagnostic probes, focused on a precise target, allowing mechanical energy transfer through the tissues and tumor ablation due to thermal and nonthermal effects. Multiple clinical trials have been performed to evaluate the safety, feasibility, and efficacy of HIFU for the palliation of pancreatic tumors, alone or in combination with chemotherapy. Tumor-related pain relief was achieved in the vast majority of reported cases, and no significant side effects were recorded. This review aims to provide a description of HIFU physical principles, briefly summarize the clinical experience, to date, in HIFU treatment of pancreatic cancer, and discuss the possible future challenges, limitations, and insights in HIFU and pancreatic cancer management.

Keywords

high-intensity focused ultrasound - pancreatic cancer - tumor ablation - pain relief - intervention

• References

• 1 Ducreux M, Cuhna AS, Caramella C. , et al; ESMO Guidelines Committee. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (Suppl. 05) v56-v68
• 2 Seufferlein T, Bachet JB, Van Cutsem E, Rougier P. ; ESMO Guidelines Working Group. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 23 (Suppl. 07) vii33-vii40
• 3 American Cancer Society. Pancreatic Cancer. https://www.cancer.org/cancer/pancreatic-cancer.html . Accessed November 24, 2018
• 4 Hammel P, Huguet F, van Laethem J-L. , et al; LAP07 Trial Group. Effect of Chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 Randomized Clinical Trial. JAMA 2016; 315 (17) 1844-1853
• 5 Conroy T, Desseigne F, Ychou M. , et al; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364 (19) 1817-1825
• 6 Trouilloud I, Dupont-Gossard AC, Malka D. , et al. Fixed-dose rate gemcitabine alone or alternating with FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) in the first-line treatment of patients with metastatic pancreatic adenocarcinoma: an AGEO randomised phase II study (FIRGEM). Eur J Cancer 2014; 50 (18) 3116-3124
• 7 Von Hoff DD, Ervin T, Arena FP. , et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369 (18) 1691-1703
• 8 Ghosn M, Farhat F, Kattan J. , et al. FOLFOX-6 combination as the first-line treatment of locally advanced and/or metastatic pancreatic cancer. Am J Clin Oncol 2007; 30 (01) 15-20
• 9 Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JAC. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer 2002; 87 (02) 161-167
• 10 IARC. World Cancer Report 2014. Geneva: World Health Organization; 2015: 350-359
• 11 Sultana A, Smith CT, Cunningham D, Starling N, Neoptolemos JP, Ghaneh P. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 2007; 25 (18) 2607-2615
• 12 Jemal A, Siegel R, Ward E. , et al. Cancer statistics, 2006. CA Cancer J Clin 2006; 56 (02) 106-130
• 13 Ilic M, Ilic I. Epidemiology of pancreatic cancer. World J Gastroenterol 2016; 22 (44) 9694-9705
• 14 Marinova M, Rauch M, Mücke M. , et al. High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity. Eur Radiol 2016; 26 (11) 4047-4056
• 15 Rombouts SJE, Vogel JA, van Santvoort HC. , et al. Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer. Br J Surg 2015; 102 (03) 182-193
• 16 Khokhlova TD, Hwang JH. HIFU for palliative treatment of pancreatic cancer. Adv Exp Med Biol 2016; 880: 83-95
• 17 Dababou S, Marrocchio C, Scipione R. , et al. High-intensity focused ultrasound for pain management in patients with cancer. Radiographics 2018; 38 (02) 603-623
• 18 Wu F. High intensity focused ultrasound: a noninvasive therapy for locally advanced pancreatic cancer. World J Gastroenterol 2014; 20 (44) 16480-16488
• 19 Li PZ, Zhu SH, He W. , et al. High-intensity focused ultrasound treatment for patients with unresectable pancreatic cancer. Hepatobiliary Pancreat Dis Int 2012; 11 (06) 655-660
• 20 Dubinsky TJ, Cuevas C, Dighe MK, Kolokythas O, Hwang JH. High-intensity focused ultrasound: current potential and oncologic applications. AJR Am J Roentgenol 2008; 190 (01) 191-199
• 21 Xu H-X. Contrast-enhanced ultrasound: the evolving applications. World J Radiol 2009; 1 (01) 15-24
• 22 Meaney PM, Zhou T, Fanning MW, Geimer SD, Paulsen KD. Microwave thermal imaging of scanned focused ultrasound heating: phantom results. Int J Hyperthermia 2008; 24 (07) 523-536
• 23 Ebbini ES, Yao H, Shrestha A. Dual-mode ultrasound phased arrays for image-guided surgery. Ultrason Imaging 2006; 28 (02) 65-82
• 24 Straube WL, Arthur RM. Theoretical estimation of the temperature dependence of backscattered ultrasonic power for noninvasive thermometry. Ultrasound Med Biol 1994; 20 (09) 915-922
• 25 Vaezy S, Shi X, Martin RW. , et al. Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging. Ultrasound Med Biol 2001; 27 (01) 33-42
• 26 Anzidei M, Marincola BC, Bezzi M. , et al. Magnetic resonance-guided high-intensity focused ultrasound treatment of locally advanced pancreatic adenocarcinoma: preliminary experience for pain palliation and local tumor control. Invest Radiol 2014; 49 (12) 759-765
• 27 Dababou S, Marrocchio C, Rosenberg J. , et al. A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound. J Ther Ultrasound 2017; 5 (01) 9
• 28 Tempany CMC, McDannold NJ, Hynynen K, Jolesz FA. Focused ultrasound surgery in oncology: overview and principles. Radiology 2011; 259 (01) 39-56
• 29 Marmottant P, Hilgenfeldt S. Controlled vesicle deformation and lysis by single oscillating bubbles. Nature 2003; 423 (6936): 153-156
• 30 Schlicher RK, Hutcheson JD, Radhakrishna H, Apkarian RP, Prausnitz MR. Changes in cell morphology due to plasma membrane wounding by acoustic cavitation. Ultrasound Med Biol 2010; 36 (04) 677-692
• 31 Sokka SD, King R, Hynynen K. MRI-guided gas bubble enhanced ultrasound heating in in vivo rabbit thigh. Phys Med Biol 2003; 48 (02) 223-241
• 32 Melodelima D, Chapelon JY, Theillère Y, Cathignol D. Combination of thermal and cavitation effects to generate deep lesions with an endocavitary applicator using a plane transducer: ex vivo studies. Ultrasound Med Biol 2004; 30 (01) 103-111
• 33 Holt RG, Roy RA. Measurements of bubble-enhanced heating from focused, MHz-frequency ultrasound in a tissue-mimicking material. Ultrasound Med Biol 2001; 27 (10) 1399-1412
• 34 van den Bijgaart RJE, Eikelenboom DC, Hoogenboom M, Fütterer JJ, den Brok MH, Adema GJ. Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies. Cancer Immunol Immunother 2017; 66 (02) 247-258
• 35 Prise KM, O'Sullivan JM. Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer 2009; 9 (05) 351-360
• 36 Rao P, Escudier B, de Baere T. Spontaneous regression of multiple pulmonary metastases after radiofrequency ablation of a single metastasis. Cardiovasc Intervent Radiol 2011; 34 (02) 424-430
• 37 Mauri G, Nicosia L, Xu Z. , et al. Focused ultrasound: tumour ablation and its potential to enhance immunological therapy to cancer. Br J Radiol 2018; 91 (1083): 20170641
• 38 Yuh EL, Shulman SG, Mehta SA. , et al. Delivery of systemic chemotherapeutic agent to tumors by using focused ultrasound: study in a murine model. Radiology 2005; 234 (02) 431-437
• 39 Liang HD, Tang J, Halliwell M. Sonoporation, drug delivery, and gene therapy. Proc Inst Mech Eng H 2010; 224 (02) 343-361
• 40 Perera RH, Hernandez C, Zhou H, Kota P, Burke A, Exner AA. Ultrasound imaging beyond the vasculature with new generation contrast agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2015; 7 (04) 593-608
• 41 Jolesz FA, Hynynen K, McDannold N, Tempany C. MR imaging-controlled focused ultrasound ablation: a noninvasive image-guided surgery. Magn Reson Imaging Clin N Am 2005; 13 (03) 545-560
• 42 Kennedy JE, ter Haar GR, Wu F. , et al. Contrast-enhanced ultrasound assessment of tissue response to high-intensity focused ultrasound. Ultrasound Med Biol 2004; 30 (06) 851-854
• 43 Wong GY, Schroeder DR, Carns PE. , et al. Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a randomized controlled trial. JAMA 2004; 291 (09) 1092-1099
• 44 Orgera G, Krokidis M, Monfardini L. , et al. High intensity focused ultrasound ablation of pancreatic neuroendocrine tumours: report of two cases. Cardiovasc Intervent Radiol 2011; 34 (02) 419-423
• 45 Petrou A, Moris D, Paul Tabet P, David Wensley Richards B, Kourounis G. Ablation of the locally advanced pancreatic cancer: an introduction and brief summary of techniques. J BUON 2016; 21 (03) 650-658
• 46 Keane MG, Bramis K, Pereira SP, Fusai GK. Systematic review of novel ablative methods in locally advanced pancreatic cancer. World J Gastroenterol 2014; 20 (09) 2267-2278
• 47 Gao HF, Wang K, Meng ZQ. , et al. High intensity focused ultrasound treatment for patients with local advanced pancreatic cancer. Hepatogastroenterology 2013; 60 (128) 1906-1910
• 48 Martin CT, Gao Y, Pugely AJ, Wolf BR. 30-day morbidity and mortality after elective shoulder arthroscopy: a review of 9410 cases. J Shoulder Elbow Surg 2013; 22 (12) 1667-1675.e1
• 49 Orgera G, Monfardini L, Della Vigna P. , et al. High-intensity focused ultrasound (HIFU) in patients with solid malignancies: evaluation of feasibility, local tumour response and clinical results. Radiol Med (Torino) 2011; 116 (05) 734-748
• 50 Zhou Y-F. High intensity focused ultrasound in clinical tumor ablation. World J Clin Oncol 2011; 2 (01) 8-27
• 51 Wang K, Chen Z, Meng Z. , et al. Analgesic effect of high intensity focused ultrasound therapy for unresectable pancreatic cancer. Int J Hyperthermia 2011; 27 (02) 101-107
• 52 Vidal-Jove J, Perich E, Del Castillo MA. Ultrasound guided high intensity focused ultrasound for malignant tumors: the Spanish experience of survival advantage in stage III and IV pancreatic cancer. Ultrason Sonochem 2015; 27: 703-706
• 53 Scott SJ, Adams MS, Salgaonkar V, Sommer FG, Diederich CJ. Theoretical investigation of transgastric and intraductal approaches for ultrasound-based thermal therapy of the pancreas. J Ther Ultrasound 2017; 5 (01) 10
• 54 Wu F. High intensity focused ultrasound ablation and antitumor immune response. J Acoust Soc Am 2013; 134 (02) 1695-1701
• 55 Zhou Q, Zhu XQ, Zhang J, Xu ZL, Lu P, Wu F. Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment. Ultrasound Med Biol 2008; 34 (01) 81-87
• 56 Kim YS, Rhim H, Choi MJ, Lim HK, Choi D. High-intensity focused ultrasound therapy: an overview for radiologists. Korean J Radiol 2008; 9 (04) 291-302
• 57 Copelan A, Hartman J, Chehab M, Venkatesan AM. High-intensity focused ultrasound: current status for image-guided therapy. Semin Intervent Radiol 2015; 32 (04) 398-415
• 58 Miller DL, Pislaru SV, Greenleaf JE. Sonoporation: mechanical DNA delivery by ultrasonic cavitation. Somat Cell Mol Genet 2002; 27 (1-6): 115-134