HIFU Reapplication in Benign Nodules

Thyroid Nodule Clinical Trial

Official title:

Efficacy and Safety of High Intensity Focused Ultrasound (HIFU) Reapplication in Benign Thyroid Nodules That Had Less-than Adequate Shrinkage Following Single-session HIFU Treatment.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03331172
• Other study ID #: UW 17-234
• Status: Completed
• Phase: N/A
• Start date: July 1, 2017
• Est. completion date: August 30, 2018

Study information

• Verified date: October 2018
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

High Intensity Focused Ultrasound (HIFU) is a new approach in treating benign thyroid nodule without surgery. It is proven effective and safe relative to traditional surgery. From previous HIFU studies, it caused shrinkage of thyroid nodule up to 70% from original size. Unfortunately, 5-10% of nodule do not shrink. Those which do not shrink are usually large in size and therefore a second HIFU treatment may help. This study is going to evaluate the efficacy and safety of reapplication HIFU after the first single HIFU session in 6 months.

The study will be carried out in the following steps:

1. Recruit subject from the clinic according to the study criteria.

2. Arrange the reapplication HIFU treatment within 3 months.

3. Arrange 4 visits after the HIFU treatment in Post 7 days, Post 1 month, Post 3 months, and Post 6 months; Data collection will be in these 4 visits through the questionnaire or interview by research assistant

4. The subjects will have further health management with the same team after the study.

Description:

Thyroid nodules are common and although most are benign and remain relatively static in size, some can grow and become large and cause local symptoms over time. In such scenario, thyroidectomy is usually indicated. However, surgery is not only associated with complications but also with high cost and general anesthesia. As a result, there has been a growing interest in exploring less invasive, non-surgical technique for benign thyroid nodules. For solid or predominantly-solid (<30% cystic areas) thyroid nodules, thermal ablation techniques have been shown to be highly effective in causing nodule shrinkage and alleviating symptoms in the long-term. To date, numerous thermal ablation techniques have been described and they include radiofrequency ablation (RFA), percutaneous laser ablation (PLA), microwave ablation and more recently, high intensity focused ultrasound (HIFU). HIFU is now considered the least invasive technique as there is no need for needle insertion into the target lesion during treatment. It works by utilizing focused ultrasound energy to generate heat and induce thermal ablation beneath the skin and other tissue layers. Recent studies (including several from our group) have shown that it is effective in not only inducing significant nodule shrinkage but also in alleviating nodule-related symptoms.

However, despite its overall success, approximately 10 - 15% of solid or predominantly solid nodules do not shrink adequately (i.e. <50% shrinkage from baseline in the first 6-12 months). Although the exact reason why some nodules do not respond remains unclear, it is noted that the majority of these less responsive nodules are larger in size / volume and so, a second or reapplication of ablation might be required to cause further shrinkage and improvement in symptoms [11]. However, the role of HIFU reapplication in nodules with less-than-adequate response (<50% at 6 months) remains undefined. As a result, the present study is aimed to the feasibility and safety of HIFU reapplication in nodules with shrinkage <50% of baseline volume 6 months after single-session HIFU treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: August 30, 2018
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• patients age older than 18 years,

• a nodule that has previously been completely treated by single-session HIFU ablation but has not responded adequately (i.e. <50% volume reduction from baseline after 6 months),

• a benign nodule without signs of malignancy (e.g, nonsuspicious clinical and US appearance, benign results at cytologic examination performed in the last 6 months, normal serum calcitonin level),

• a nodule measuring on US greater than or equal to 10 mm in three orthogonal dimensions,

• less than 30% of the targeted nodule comprising cystic area,

• HIFU accessibility of the targeted nodule (distance between the skin and the anterior surface of the nodule less than 17 mm, with no interference of the collarbone with HIFU unit movements)

• normal thyrotropin concentration and

• absence of vocal cord immobility at laryngoscopy.

Exclusion Criteria:

• head and/or neck disease preventing hyperextension of the neck,

• history of thyroid cancer or other malignant tumors in the neck region,

• history of neck irradiation,

• intranodular macrocalcifications inducing a shadow substantial enough to preclude treatment with HIFU,

• nodules next to the posterior margin of the thyroid lobe with anteroposterior diameter less than 15 mm,

• pregnancy or lactation,

• any contraindication related to intravenous moderate sedation in the first HIFU treatment.

Related Conditions & MeSH terms

• Thyroid Diseases
• Thyroid Nodule

Intervention

Device:
• Echopulse
Echopulse is a real-time US-guided High-intensity focused ultrasound (HIFU) system, the HIFU session is a noninvasive procedure that involves application of a focused high-energy ultrasound beam for thermal tissue ablation inside the targeted zone, with minimal effect on the surrounding tissue

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (10)

Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S, Attard M, Lamartina L, Nicolucci A, Filetti S. The natural history of benign thyroid nodules. JAMA. 2015 Mar 3;313(9):926-35. doi: 10.1001/jama.2015.0956. — View Citation

Gharib H, Hegedüs L, Pacella CM, Baek JH, Papini E. Clinical review: Nonsurgical, image-guided, minimally invasive therapy for thyroid nodules. J Clin Endocrinol Metab. 2013 Oct;98(10):3949-57. doi: 10.1210/jc.2013-1806. Epub 2013 Aug 16. Review. — View Citation

Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L, Paschke R, Valcavi R, Vitti P; AACE/ACE/AME Task Force on Thyroid Nodules. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES--2016 UPDATE. Endocr Pract. 2016 May;22(5):622-39. doi: 10.4158/EP161208.GL. — View Citation

Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 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 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020. Review. — View Citation

Huh JY, Baek JH, Choi H, Kim JK, Lee JH. Symptomatic benign thyroid nodules: efficacy of additional radiofrequency ablation treatment session--prospective randomized study. Radiology. 2012 Jun;263(3):909-16. doi: 10.1148/radiol.12111300. Epub 2012 Mar 21. — View Citation

Jeong WK, Baek JH, Rhim H, Kim YS, Kwak MS, Jeong HJ, Lee D. Radiofrequency ablation of benign thyroid nodules: safety and imaging follow-up in 236 patients. Eur Radiol. 2008 Jun;18(6):1244-50. doi: 10.1007/s00330-008-0880-6. Epub 2008 Feb 20. — View Citation

Korkusuz H, Sennert M, Fehre N, Happel C, Grünwald F. Local thyroid tissue ablation by high-intensity focused ultrasound: effects on thyroid function and first human feasibility study with hot and cold thyroid nodules. Int J Hyperthermia. 2014 Nov;30(7):480-5. doi: 10.3109/02656736.2014.962626. Epub 2014 Oct 14. — View Citation

Kovatcheva RD, Vlahov JD, Stoinov JI, Zaletel K. Benign Solid Thyroid Nodules: US-guided High-Intensity Focused Ultrasound Ablation-Initial Clinical Outcomes. Radiology. 2015 Aug;276(2):597-605. doi: 10.1148/radiol.15141492. Epub 2015 Mar 13. — View Citation

Lang BH, Woo YC, Wong CKH. High-Intensity Focused Ultrasound for Treatment of Symptomatic Benign Thyroid Nodules: A Prospective Study. Radiology. 2017 Sep;284(3):897-906. doi: 10.1148/radiol.2017161640. Epub 2017 Apr 18. — View Citation

Sung JY, Baek JH, Kim KS, Lee D, Yoo H, Kim JK, Park SH. Single-session treatment of benign cystic thyroid nodules with ethanol versus radiofrequency ablation: a prospective randomized study. Radiology. 2013 Oct;269(1):293-300. doi: 10.1148/radiol.13122134. Epub 2013 Apr 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in thyroid nodule volume (mL)	To measure the change in volume (mL) of the index (or treated) thyroid nodule 6 months following HIFU reapplication	6 months
Secondary	The efficacy of reapplication HIFU after the first single session in 6 months	To compare the change in volume (mL) of the treated thyroid nodule between the first single session and the reapplication.	6 months
Secondary	The safety of reapplication HIFU after the first single session in 6 months	To assess the safety of reapplication HIFU by recording any complications after the treatment	6 months
Secondary	The rate of vocal cord palsy in reapplication HIFU after the first single session in 6 months	To examine the rate of vocal cord palsy in reapplication HIFU after the first single session in 6 month	6 months
Secondary	The cosmetic score (in 0-10) of reapplication HIFU after the first single session in 6 months	To evaluate the cosmetic score (in 0-10) of reapplication HIFU after the first single session in 6 months	6 months
Secondary	The pain score (in 0-10) of reapplication HIFU after the first single session in 6 months	To evaluate the pain score (in 0-10) of reapplication HIFU after the first single session in 6 month	6 months
Secondary	The satisfactory (in 0-10) of reapplication HIFU after the first single session in 6 month	The satisfactory level, from scoring in 0-10, to examine how participants' satisfaction in the reapplication HIFU after the first single session in 6 months	6 months