Pancreatic Tumors, Malignant

Last Updated:

Focused Ultrasound Therapy

Focused ultrasound is a 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. 

Advantages
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.

Clinical Trials

A clinical trial in Japan is using focused ultrasound to enhance chemotherapy in patients with pancreatic cancer.

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. 

See a list of treatment sites >
See a list of clinical trials sites >
See a list of laboratory research sites >

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.

      Additional Resources

      Notable Papers

      Suggested Reading: Focused Ultrasound for Pancreatic Cancer (PDF), July 2019.

      Imran KM, Gannon J, Morrison HA, Tupik JD, Tintera B, Nagai-Singer MA, Ivester H, Madanick JM, Hendricks-Wenger A, Uh K, Luyimbazi DT, Edwards M, Coutermarsh-Ott S, Eden K, Byron C, Clark-Deener S, Lee K, Vlaisavljevich E, Allen IC. Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy. Ultrasound Med Biol. 2023 Nov;49(11):2361-2370. doi: 10.1016/j.ultrasmedbio.2023.07.013. Epub 2023 Aug 16. PMID: 37596154 

      Yang Y, Shi XQ, Chen G, Qian LX. Risk factors for unresectable pancreatic cancer following high-intensity focused ultrasound treatment. Cancer Med. 2023 Oct;12(19):19537-19547. doi: 10.1002/cam4.6568. Epub 2023 Oct 4. PMID: 37792639 

      Spiers L, Gray M, Lyon P, Sivakumar S, Bekkali N, Scott S, Collins L, Carlisle R, Wu F, Middleton M, Coussios C. Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound. BMC Cancer. 2023 Sep 23;23(1):896. doi: 10.1186/s12885-023-11228-z. PMID: 37741968 

      Yang C, Guo J, Chen L, Zhang L, Zhang L, Li K, Chen J, Chen W. The dose of focused ultrasound ablation surgery (FUAS) for unresectable pancreatic cancer is predictable: A multicenter retrospective study. Medicine (Baltimore). 2023 Sep 22;102(38):e34684. doi: 10.1097/MD.0000000000034684. PMID: 37746965 

      De Grandis MC, Ascenti V, Lanza C, Di Paolo G, Galassi B, Ierardi AM, Carrafiello G, Facciorusso A, Ghidini M. Locoregional Therapies and Remodeling of Tumor Microenvironment in Pancreatic Cancer. Int J Mol Sci. 2023 Aug 11;24(16):12681. doi: 10.3390/ijms241612681. PMID: 37628865 

      Imran KM, Gannon J, Morrison HA, Tupik JD, Tintera B, Nagai-Singer MA, Ivester H, Madanick JM, Hendricks-Wenger A, Uh K, Luyimbazi DT, Edwards M, Coutermarsh-Ott S, Eden K, Byron C, Clark-Deener S, Lee K, Vlaisavljevich E, Allen IC. Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy. Ultrasound Med Biol. 2023 Aug 16:S0301-5629(23)00245-4. doi: 10.1016/j.ultrasmedbio.2023.07.013. PMID: 37596154 

      Wang R, Yao Y, Gao Y, Liu M, Yu Q, Song X, Han X, Niu D, Jiang L. CD133-Targeted Hybrid Nanovesicles for Fluorescent/Ultrasonic Imaging-Guided HIFU Pancreatic Cancer Therapy. Int J Nanomedicine. 2023 May 12;18:2539-2552. doi: 10.2147/IJN.S391382. eCollection 2023. PMID: 37207110 

      Imran KM, Tintera B, Morrison HA, Tupik JD, Nagai-Singer MA, Ivester H, Council-Troche M, Edwards M, Coutermarsh-Ott S, Byron C, Clark-Deener S, Uh K, Lee K, Boulos P, Rowe C, Coviello C, and Allen IC. Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study Pharmaceutics 2023, 15(6), 1585. May 2023  doi.org/10.3390/pharmaceutics15061585 

      Khokhlova TD, Wang YN, Son H, Totten S, Whang S, Ha Hwang J. Chronic effects of pulsed high intensity focused ultrasound aided delivery of gemcitabine in a mouse model of pancreatic cancer. Ultrasonics. 2023 Apr 13;132:106993. doi: 10.1016/j.ultras.2023.106993.

      Lee JY, Oh DY, Lee KH, Lee SH, Lee DH, Kang K, Kang SY, Park DH. Combination of chemotherapy and focused ultrasound for the treatment of unresectable pancreatic cancer: a proof-of-concept study. Eur Radiol. 2023 Apr;33(4):2620-2628. doi: 10.1007/s00330-022-09271-8. Epub 2022 Dec 8.

      Haram M, Snipstad S, Berg S, Mjønes P, Rønne E, Lage J, Mühlenpfordt M, Davies CL. Ultrasound and Microbubbles Increase the Uptake of Platinum in Murine Orthotopic Pancreatic Tumors. Ultrasound Med Biol. 2023 Feb 24:S0301-5629(23)00026-1. doi: 10.1016/j.ultrasmedbio.2023.01.014.

      Ning J, Wang S, Guo Y, Diao J, Bai X, Wang H, Hu K, Zhao Q. High Intensity Focused Ultrasound Ablation for Patients With Locally Advanced Pancreatic Adenocarcinoma: A Propensity Score-Matching Analysis. J Ultrasound Med. 2023 Jan 24. doi: 10.1002/jum.16181.

      Wang J, Fite BZ, Kare AJ, Wu B, Raie M, Tumbale SK, Zhang N, Davis RR, Tepper CG, Aviran S, Newman AM, King DA, Ferrara KW. Multiomic analysis for optimization of combined focal and immunotherapy protocols in murine pancreatic cancer. Theranostics. 2022 Nov 14;12(18):7884-7902. doi: 10.7150/thno.73218. eCollection 2022.

      Lee JY, Oh DY, Lee KH, Lee SH, Lee DH, Kang K, Kang SY, Park DH. Combination of chemotherapy and focused ultrasound for the treatment of unresectable pancreatic cancer: a proof-of-concept study. Eur Radiol. 2022 Dec 8. doi: 10.1007/s00330-022-09271-8. Online ahead of print.

      Joiner JB, Kren NP, Durham PG, McRee AJ, Dayton PA, Pylayeva-Gupta Y. Low-Intensity Focused Ultrasound Produces Immune Response in Pancreatic Cancer. Ultrasound Med Biol. 2022 Nov;48(11):2344-2353. doi: 10.1016/j.ultrasmedbio.2022.06.017. Epub 2022 Aug 24.

      Gray M, Spiers L, Coussios C. Effects of human tissue acoustic properties, abdominal wall shape, and respiratory motion on ultrasound-mediated hyperthermia for targeted drug delivery to pancreatic tumors. Int J Hyperthermia. 2022 Dec;39(1):918-934. doi: 10.1080/02656736.2022.2091799.

      Sofuni A, Asai Y, Mukai S, Yamamoto K, Itoi T. High-intensity focused ultrasound therapy for pancreatic cancer. J Med Ultrason (2001). 2022 May 12. doi: 10.1007/s10396-022-01208-4.

      Mouratidis PXE, Ter Haar G. Latest Advances in the Use of Therapeutic Focused Ultrasound in the Treatment of Pancreatic Cancer. Cancers (Basel). 2022 Jan 27;14(3):638. doi: 10.3390/cancers14030638.

      Yang Y, Shi XQ, Chen G, Zhou XN, Qian LX. Contrast-enhanced ultrasound for evaluating response to pulsed-wave high-intensity focused ultrasound therapy in advanced pancreatic cancer. Clin Hemorheol Microcirc. 2022 Jan 5. doi: 10.3233/CH-211342.

      Fergadi MP, Magouliotis DE, Rountas C, Vlychou M, Athanasiou T, Symeonidis D, Pappa PA, Zacharoulis D. A meta-analysis evaluating the role of high-intensity focused ultrasound (HIFU) as a fourth treatment modality for patients with locally advanced pancreatic cancer. Abdom Radiol (NY). 2021 Oct 31. doi: 10.1007/s00261-021-03334-y.

      Guo J, Wang Y, Chen J, Qiu W, Chen W. Systematic review and trial sequential analysis of high-intensity focused ultrasound combined with chemotherapy versus chemotherapy in the treatment of unresectable pancreatic ductal adenocarcinoma. Int J Hyperthermia. 2021;38(1):1375-1383. doi: 10.1080/02656736.2021.1962550.

      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.

      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.

      Click here for additional references from PubMed. 

      International Approval
      Clinical Trials