Focused Ultrasound Therapy
Focused ultrasound is an early stage, noninvasive therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with pancreatic tumors. This novel technology focuses beams of ultrasound energy precisely and accurately on targets deep in the body without damaging surrounding normal tissue.
How it Works
Where the beams converge, focused ultrasound can produce a couple of effects. One is ablation, or thermal destruction of tissue. The goal could be complete ablation of the cancer or it can be done partially, and partial ablation may help awaken the immune system for a more generalized response. This ablation can also be targeted at the innervation of the pancreas, to help lessen the pain from the disease. A second approach is to treat the targeted tissue to enable enhanced absorption of chemotherapy.
Current treatment options are focused on pancreatic cancer, and include combinations of surgery, radiation, chemotherapy, embolization or other ablative methods, yet these still not very effective for many patients.
Focused ultrasound – used alone and in combination with other therapies – is being investigated to treat pancreatic cancer and the pain associated with the disease. Focused ultrasound has the potential to achieve symptomatic relief by improving the resection of the tumor prior to surgery, by reducing tumor size and spread, and by reduction in overall tumor pain.
For certain patients, focused ultrasound could provide a noninvasive alternative to surgery with less risk of complications – such as surgical wound healing or infection – at a lower cost. It can reach the desired target without damaging surrounding tissue and is repeatable, if necessary.
Focused ultrasound can also be a complement to drug therapy, enabling enhanced delivery of chemotherapy or immunotherapy to tumors. It may potentially induce an anti-tumor immune response.
A clinical trial has begun in Stanford, California, that is treating patients with adenocarcinoma of the pancreas.
A clinical trial in Oxford, UK, will treat patients with pancreatic cancer with focused ultrasound. Those interested in learning more about this trial can contact the site's study coordinator.
The University of Roma La Sapienza is leading a study to assess the feasibility and clinical performance of focused ultrasound ablation of unresectable pancreatic cancer in pain palliation and tumor control.
A clinical trial in Norway is using focused ultrasound with microbubbles to enhance the uptake of chemotherapy in patients with pancreatic ductal adenocarcinoma.
The Focused Ultrasound Foundation has established the ARRAY registry to capture data from pancreatic cancer patients to help guide future decisions about optimal clinical care, safety and regulatory factors, and reimbursement concerns. The goal of this registry is to capture early data to expedite the availability of focused ultrasound improvements for patient care as soon as possible.
Researchers in Japan are using sonodynamic therapy to release chemotherapeutic agents in patients with pancreatic cancer.
Regulatory Approval and Reimbursement
The Model JC system manufactured by Chongqing Haifu has been approved in Europe for palliative treatment in patients with pancreatic cancer.
Focused ultrasound treatment for patients with pancreatic cancer is not universally reimbursed by medical insurers.
Preclinical Laboratory Studies
Preclinical studies are underway to investigate the use of non-ablation mechanisms of focused ultrasound in the treatment of pancreatic cancer. Examples of these studies include:
- Focused ultrasound to induce an immune response that could be combined with immunotherapeutics to treat both local and systemic disease.
- Focused ultrasound to enable targeted delivery and/or activation of drugs via carrier vehicles (e.g. microbubbles, nanoparticles, liposomes) to enable delivery of high concentrations in the tumor with minimal systemic side effects.
Suggested Reading: Focused Ultrasound for Pancreatic Cancer (PDF), July 2019.
Stanislavova N, Karamanliev M, Ivanov T, Yotsov T, Zhou K, Dimitrov D. Is high-intensity focused ultrasound (HIFU) an option for neoadjuvant therapy for borderline resectable pancreatic cancer patients? - a systematic review. Int J Hyperthermia. 2021 Sep;38(2):75-80. doi: 10.1080/02656736.2021.1909150.
Mouratidis PXE, Costa M, Rivens I, Repasky EE, Ter Haar G. Pulsed focused ultrasound can improve the anti-cancer effects of immune checkpoint inhibitors in murine pancreatic cancer. J R Soc Interface. 2021 Jul;18(180):20210266. doi: 10.1098/rsif.2021.0266. Epub 2021 Jul 7.
Tonguc T, Strunk H, Gonzalez-Carmona MA, Recker F, Lütjohann D, Thudium M, Conrad R, Becher MU, Savchenko O, Davidova D, Luechters G, Mustea A, Strassburg CP, Attenberger U, Pieper CC, Jenne J, Marinova M. US-guided high-intensity focused ultrasound (HIFU) of abdominal tumors: outcome, early ablation-related laboratory changes and inflammatory reaction. A single-center experience from Germany. Int J Hyperthermia. 2021 Sep;38(2):65-74. doi: 10.1080/02656736.2021.1900926.
Zhao J, Shen H, Hu X, Wang Y, Yuan Y. The efficacy of a new high-intensity focused ultrasound therapy for metastatic pancreatic cancer. Int J Hyperthermia. 2021;38(1):288-295. doi: 10.1080/02656736.2021.1876252.
Fabritius M, Lambin T, Cao E, Robert J, Milot L, Lafon C, Pioche M. High intensity focused ultrasound: a future alternative to surgery for the treatment of localized pancreatic tumors? Endoscopy. 2021 Feb 16. doi: 10.1055/a-1338-0293.
Marinova M, Feradova H, Gonzalez-Carmona MA, Conrad R, Tonguc T, Thudium M, Becher MU, Kun Z, Gorchev G, Tomov S, Strassburg CP, Attenberger U, Schild HH, Dimitrov D, Strunk HM. Improving quality of life in pancreatic cancer patients following high-intensity focused ultrasound (HIFU) in two European centers. Eur Radiol. 2021 Jan 23. doi: 10.1007/s00330-020-07682-z.
Dan Z, Yi F, Qi Z, Yi-Jie Q, Xiao-Fan T, Shuai-Nan S, Yi D, Tian-Shu L, Wen-Ping W. The value of dynamic contrast enhanced ultrasound (DCE-US) in monitoring treatment effect of high-intensity focused ultrasound (HIFU) in locally advanced pancreatic cancer (LAPC). Clin Hemorheol Microcirc. 2020 Nov 25. doi: 10.3233/CH-201020.
Kang HJ, Lee JY, Park EJ, Lee HJ, Ha SW, Ahn YD, Cheon Y, Han JK. Synergistic Effects of Pulsed Focused Ultrasound and a Doxorubicin-Loaded Microparticle-Microbubble Complex in a Pancreatic Cancer Xenograft Mouse Model. Ultrasound Med Biol. 2020 Aug 20:S0301-5629(20)30334-3. doi: 10.1016/j.ultrasmedbio.2020.07.019.
Sebeke LC, Rademann P, Maul AC, Schubert-Quecke C, Annecke T, Yeo SY, Castillo-Gómez JD, Schmidt P, Grüll H, Heijman E. Feasibility study of MR-guided pancreas ablation using high-intensity focused ultrasound in a healthy swine model. Int J Hyperthermia. 2020;37(1):786-798. doi: 10.1080/02656736.2020.1782999.
Thudium M, Bette B, Tonguc T, Ghaei S, Conrad R, Becher MU, Mücke M, Luechters G, Strunk H, Marinova M. Multidisciplinary management and outcome in pancreatic cancer patients treated with high-intensity focused ultrasound. Int J Hyperthermia. 2020;37(1):456-462. doi: 10.1080/02656736.2020.1762006.
Guo X, Zhu H, Zhou K, Jin C, Yang Y, Zhang J, Yang W, Ran L, Dimitrov DD. Effects of high-intensity focused ultrasound treatment on peripancreatic arterial and venous blood vessels in pancreatic cancer. Oncol Lett. 2020 Jun;19(6):3839-3850. doi: 10.3892/ol.2020.11511. Epub 2020 Apr 3.
Yu Q, Yao Y, Zhu X, Gao Y, Chen Y, Wang R, Xu P, Wei X, Jiang L. In Vivo Flow Cytometric Evaluation of Circulating Metastatic Pancreatic Tumor Cells after High-Intensity Focused Ultrasound Therapy. Cytometry A. 2020 Apr 19. doi: 10.1002/cyto.a.24014.
Maloney E, Wang YN, Vohra R, Son H, Whang S, Khokhlova T, Park J, Gravelle K, Totten S, Hwang JH, Lee D. Magnetic resonance imaging biomarkers for pulsed focused ultrasound treatment of pancreatic ductal adenocarcinoma. World J Gastroenterol. 2020 Mar 7;26(9):904-917. doi: 10.3748/wjg.v26.i9.904.
Dimitrov D, Stanislavova N, Yotsov T, Zhou K. Recurrent pancreatic cancer patient treated by chemotherapy and focused ultrasound surgery. A case report. Med Ultrason. 2019 Aug 15. doi: 10.11152/mu-2031.
Sofuni A, Fujita M, Asai Y, Tsuchiya T, Ishii K, Tanaka R, Tonozuka R, Honjo M, Mukai S, Nagai K, Yamamoto K, Matsunami Y, Kurosawa T, Kojima H, Itoi T. A Case of Unresectable Pancreatic Cancer with Long-Term Survival in High-Intensity Focused Ultrasound (HIFU) Therapy. Ultrasound Int Open. 2019 Nov;5(3):E89-E92. doi: 10.1055/a-1061-7790. Epub 2020 Jan 8.
Razavi M, Zheng F, Telichko A, Ullah M, Dahl J, Thakor AS. Effect of Pulsed Focused Ultrasound on the Native Pancreas. Ultrasound Med Biol. 2019 Dec 24. pii: S0301-5629(19)31598-4. doi: 10.1016/j.ultrasmedbio.2019.11.016.
Moulla Y, Petersen TO, Maiwald B, Balis N, Kreuser N, Lordick F, Seehofer D, Sucher R, Hecker M, Hoffmeister A, Jansen-Winkeln B, Gockel I. [Ablative treatment options for locally advanced unresectable and borderline resectable pancreatic carcinoma]. Chirurg. 2019 Dec 11. doi: 10.1007/s00104-019-01072-y. Review. German.
Tao SF, Gu WH, Gu JC, Zhu ML, Wang Q, Zheng LZ. A Retrospective Case Series Of High-Intensity Focused Ultrasound (HIFU) In Combination With Gemcitabine And Oxaliplatin (Gemox) On Treating Elderly Middle And Advanced Pancreatic Cancer. Onco Targets Ther. 2019 Nov 15;12:9735-9745. doi: 10.2147/OTT.S220299. eCollection 2019.
Focused Ultrasound Foundation Workshop. The Role of Focused Ultrasound in Pancreatic Cancer, 2019.
Zhu B, Li J, Diao L, Ma K, Fan Y, Yang W. High-intensity focused ultrasound ablation for advanced pancreatic cancer. J Cancer Res Ther. 2019;15(4):831-835. doi: 10.4103/jcrt.JCRT_408_18.
Ning Z, Zhu Z, Wang H, Zhang C, Xu L, Zhuang L, Yan X, Wang D, Wang P, Meng Z. High-intensity focused ultrasound enhances the effect of bufalin by inducing apoptosis in pancreatic cancer cells. Onco Targets Ther. 2019 Feb 12;12:1161-1170. doi: 10.2147/OTT.S185953. eCollection 2019.
Saccomandi P, Lapergola A, Longo F, Schena E, Quero G. Thermal ablation of pancreatic cancer: A systematic literature review of clinical practice and pre-clinical studies. Int J Hyperthermia. 2018 Nov 14:1-21. doi: 10.1080/02656736.2018.1506165.
Nabavizadeh A, Payen T, Saharkhiz N, McGarry M, Olive KP, Konofagou EE. Technical Note: Feasibility of the In vivo Young's modulus visualization of pancreatic ductal adenocarcinoma during HIFU ablation Using Harmonic Motion Elastography (HME) in vivo. Med Phys. 2018 Sep 4. doi: 10.1002/mp.13170.
Marinova M, Huxold HC, Henseler J, Mücke M, Conrad R, Rolke R, Ahmadzadehfar H, Rauch M, Fimmers R, Luechters G, Cuhls H, Radbruch L, Schild HH, Strunk H. Clinical Effectiveness and Potential Survival Benefit of US-Guided High-Intensity Focused Ultrasound Therapy in Patients with Advanced-Stage Pancreatic Cancer. Ultraschall Med. 2018 Apr 17. doi: 10.1055/a-0591-3386.
Park EJ, Ahn YD, Lee JY. In vivo study of enhanced chemotherapy combined with ultrasound image-guided focused ultrasound (USgFUS) treatment for pancreatic cancer in a xenograft mouse model. Eur Radiol. 2018 Mar 29. doi: 10.1007/s00330-018-5355-9.
Strunk HM, Lützow C, Henseler J, Mücke M, Rauch M, Marx C, Schild HH, Marinova M. Mesenteric Vessel Patency Following HIFU Therapy in Patients with Locally Invasive Pancreatic Cancer. Panc ca Ultraschall Med. 2018 Jan 18. doi: 10.1055/s-0043-125391.
Click here for additional references from PubMed.