Effectiveness of High-intensity Focused Ultrasound (HIFU) Therapy of Solid and Complex Benign Thyroid Nodules – A Long-term Follow up Two-center Study

Abstract

Purpose To investigate the effectiveness of high-intensity focused ultrasound (HIFU) of solid and complex benign thyroid nodules.

Methods Fifty-eight patients with benign thyroid nodules were treated with HIFU at two centers from 2014–2019. The device, EchoPulse (Teraclion, Malakoff, France), heats the nodes to 80–90 °C. Nodal volumes were measured by ultrasound at regular intervals before and up to 12 months after therapy. In a retrospective long-term two-center study, average volume reductions in relation to baseline volume were statistically analyzed by the Wilcoxon signed-rank test. Side effects were documented.

Results In solid nodules, the average percent volume reductions at the 3, 6, 9, and 12-months follow-up were 49.98%, 46.40%, 65.77%, and 63.88%, respectively. The results were significant with p<0.05 in the Wilcoxon signed-rank test at the 3, 6, and 9-months follow-up. In complex nodules, the average percent volume reduction was 35.2% at 3 months, 36.89% at 6 months, and 63.64% at twelve months follow up. The results were significant with p<0.05 in the Wilcoxon signed-rank test at the 3- and 6-months follow-up. The complication rate was 5.2%. All complications occurred in patients with solid nodules.

Conclusion The study showed that HIFU is an effective treatment method for both solid and complex nodules. The complication rate is relatively high at 5.2%. No long-term complications occurred. The solid nodules responded better to HIFU than complex nodules.

Key words

thermoablation - nodal morphology - volume reduction - therapeutic effect

Publication History

Received: 01 June 2021
Received: 18 November 2021

Accepted: 06 December 2021

Article published online:
10 January 2022

• References

• 1 Papini E, Monpeyssen H, Frasoldati A. et al. 2020 European Thyroid Association Clinical Practice Guideline for the use of image-guided ablation in benign thyroid nodules. Eur Thyroid J 2020; 9: 172-185
• 2 Haugen BR, Alexander EK, Bible KC. et al. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016; 26: 1-133
• 3 Ha EJ, Lim HK, Yoon JH. et al. Primary imaging test and appropriate biopsy methods for thyroid nodules: Guidelines by Korean Society of Radiology and National Evidence-Based Healthcare Collaborating Agency. Korean J Radiol 2018; 19: 623-631
• 4 Dobnig H. (2015): Schilddrusenknoten und Schilddruse. Österreichische Ärztezeitung 2015; 19: 26-34
• 5 Lang BHH, Wu ALH. High intensity focused ultrasound (HIFU) ablation of benign thyroid nodules – A systematic review. J Ther Ultrasound 2017; 5: 11
• 6 Durante C, Costante G, Lucisano G. et al. The natural history of benign thyroid nodules. JAMA 2015; 313: 926
• 7 Federführende Fachgesellschaft: Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV), Operative Therapie benigner Schilddrüsenerkrankungen. AWMF online 2015
• 8 Dietlein M, Grünwald F, Schmidt M. et al. Radioiodtherapie bei benignen Schilddrüsenerkrankungen (Version 5). Nuklearmedizin 2016; 55: 213-220
• 9 Korkusuz H, Gröner D, Racynski N. et al. Thermal ablation of thyroid nodules: Are radiofrequency ablation, microwave ablation and high intensity focused ultrasound equally safe and effective methods?. Eur Radiol 2018; 28: 929-935
• 10 Chung SR, Baek JH, Suh CH. et al. Efficacy and safety of high-intensity focused ultrasound (HIFU) for treating benign thyroid nodules: A systematic review and meta-analysis. SAGE Journals 2020; 61: 1636-1643
• 11 Korkusuz H. Thermoablation von schilddrüsenknoten. Nuklearmediziner 2016; 39: 227-231
• 12 Trimboli P, Pelloni F, Bini F. et al. High-intensity focused ultrasound (HIFU) for benign thyroid nodules: 2-year follow-up results. Endocrine 2019; 65: 312-317
• 13 Korkusuz H, Fehre N, Sennert M. et al. Volume reduction of benign thyroid nodules 3 months after a single treatment with high-intensity focused ultrasound (HIFU). J Ther Ultrasound 2015; 3: 4
• 14 Korkusuz H, Sennert M, Fehre N. et al. Localized thyroid tissue ablation by high intensity focused ultrasound: Volume reduction, effects on thyroid function and immune response. Fortschr Röntgenstr 2015; 187: 1011-1015
• 15 Sennert M, Happel C, Korkusuz Y. et al. Further investigation on high-intensity focused ultrasound (HIFU) treatment for thyroid nodules. Acad Radiol 2018; 25: 88-94
• 16 Hill CR, Haar GR. Review article: High intensity focused ultrasound–potential for cancer treatment. Br J Radiol 1995; 68: 1296-1303
• 17 Yang R, Sanghvi NT, Rescorla FJ. et al. Liver cancer ablation with extracorporeal high-intensity focused ultrasound. Eur Urol 1993; 23: 17-22
• 18 Wu F, Wang ZB, Cao YD. et al. A randomised clinical trial of high-intensity focused ultrasound ablation for the treatment of patients with localised breast cancer. Br J Cancer 2003; 89: 2227-2233
• 19 Lorton O, Guillemin P, Holman R. et al. Enhancement of HIFU thermal therapy in perfused tissue models using micron-sized FTAC-stabilized PFOB-core endovascular sonosensitizers. Int J Hyprth 2020; 37: 1116-1130
• 20 Zhong X, Mei Z, Tian Z. et al. The study of enhanced high-intensity focused ultrasound therapy by sonodynamic N2O microbubbles. Nanoscale Res Lett 2019; 14: 381
• 21 Spartalis E, Karagiannis SP, Plakopitis N. et al. Single-session high-intensity focused ultrasound (HIFU) ablation for benign thyroid nodules: A systematic review. Expert Rev Med Devices 2020; 17: 1-13
• 22 Izadifar Z, Izadifar Z, Chapman D. et al. An introduction to high intensity focused ultrasound: Systematic review on principles, devices, and clinical applications. J Clin Med 2020; 9: 460
• 23 Trimboli P, Bini F, Marinozzi F. et al. High-intensity focused ultrasound (HIFU) therapy for benign thyroid nodules without anesthesia or sedation. Endocrine 2018; 61: 210-215
• 24 Bryan R. et al. American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer, Thyroid 2016; 26: 1-133
• 25 Cibas ES, Ali SZ. The 2017 Bethesda System for reporting thyroid cytopathology. Thyroid 2017; 27: 1341-1346
• 26 Wen-Bo L. et al. Comparison between thin-slice 3-D volumetric ultrasound and conventional ultrasound in the differentiation of benign and malignant thyroid esions. Ultrasound Med Biol 2015; 41: 3096-3101
• 27 Andrioli M, Carzaniga C, Persani L. et al. Standardized ultrasound report for thyroid nodules: The endocrinologist's viewpoint. Eur Thyroid J 2013; 2: 37-48
• 28 Mi-Jung Lee. et. al. Partially cystic thyroid nodules on ultrasound: Probability of malignancy and sonographic differentiation. Thyroid 2009; 19: 341-346
• 29 Liu X, Li J, Gong X, Zhang D. Nonlinear absorption in biological tissue for high intensity focused ultrasound. Ultrasonics 2006; 44: 27-30
• 30 Bailey MR, Khokhlova VA, Sapozhnikov OA. et al. Physical mechanisms of the therapeutic effect of ultrasound (a review). Acoust Phys 2003; 49: 369-388
• 31 Haar G, Coussios C. High intensity focused ultrasound: Physical principles and devices. Int J Hypertherm 2007; 23: 89-104
• 32 Namakshenas P, Mojra A. Microstructure-based non-Fourier heat transfer modeling of HIFU treatment for thyroid cancer. Comput Methods Programs Biomed 2020; 197: 105698
• 33 Jin C, He ZZ, Yang Y, Liu J. MRI-based three-dimensional thermal physiological characterization of thyroid gland of human body. Med Eng Phys 2014; 36: 16-25
• 34 Yue W, Wang S, Wang B. et al. Ultrasound guided percutaneous microwave ablation of benign thyroid nodules: Safety and imaging follow-up in 222 patients. Eur J Radiol 2013; 82: e11-e16
• 35 Lim HK, Lee JH, Ha EJ. et al. Radiofrequency ablation of benign non-functioning thyroid nodules: 4-year follow-up results for 111 patients. European Radiol 2013; 23: 1044-1049
• 36 Baek JH, Ha EJ, Choi YJ. et al. Radiofrequency versus ethanol ablation for treating predominantly cystic thyroid nodules: A randomized clinical trial. Korean J Radiol 2015; 16: 1332-1340
• 37 Jung HB, Yoon SK, Ducky L. et al. Benign predominantly solid thyroid nodules: Prospective study of efficacy of sonographically guided radiofrequency ablation versus control condition. AJR AM J Roentgenol 2010; 194: 1137-1142