HIFU Reapplication in Benign Nodules

Study Overview
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Brief Summary
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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: Recruit subject from the clinic according to the study criteria. Arrange the reapplication HIFU treatment within 3 months. 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 The subjects will have further health management with the same team after the study.

Detailed Description
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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.

Official Title
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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.

Conditions
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Thyroid Nodule

Intervention / Treatment
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* Device: Echopulse


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Intensity Focused Ultrasound<br> | Device: Echopulse<br>* 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<br>* Other names: High Intensity Focused Ultrasound (HIFU);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIFU, thyroid nodule, Benign, Reapplication