Thermal Ablation of Cervical Metastases From Thyroid Carcinoma

Study Overview
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Brief Summary
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This study will evaluate the clinical response and safety of ultrasound guided percutaneous thermal ablation of lymph node metastases from thyroid carcinoma as an alternative to surgical treatment. The ablation of cervical lymph node metastases from differentiated thyroid carcinoma or medullary thyroid carcinoma will be directed to lesions larger than 0.8 cm, using ultrasound-guided radiofrequency ablation (RFA), laser ablation (LA) or cryoablation (Cryo) techniques, randomly assigned. Clinical and ultrasound monitoring will be carried out during 24 months, with examinations before the ablation procedure, immediately after including contrast-enhanced ultrasound (CEUS) when applicable, and B-mode, color Doppler and Shear-Wave elastography ultrasound follow up with 6, 12, and 24 months.

Detailed Description
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Thyroidectomy is the main treatment of well differentiated thyroid carcinoma. Residual or recurrent cervical metastases are common (9-20% of patients during long-term follow up). Thermal ablation of cervical metastatic lymph nodes from thyroid carcinoma has been proposed in research centers as an option for the treatment of patients who remain with metastatic disease in cervical lymph nodes, despite thyroidectomy with or without neck dissection associated with radioiodine treatment. Potential advantages from percutaneous thermal ablation are related to less complication rates, less morbidity, possibility of outpatient treatment modality, and less global treatment costs when compared to the surgical approach. Aims of the study: To evaluate safety and efficacy of ultrasound-guided thermal ablation in the treatment of cervical lymph node metastases from differentiated thyroid carcinoma To evaluate the best response to thermal ablation defined as lymph node reduction or volume stability after ablation To evaluate the CEUS patterns of lymph nodes before and after ablation To evaluate the elastography patterns of lymph nodes before and after ablation To evaluate the tumor marker response after ablation To evaluate the contribution of thermal ablation to decrease additional therapeutic procedures To compare differences between LA, RFA and cryoablation in terms of complications, side effects and tolerability Patients with cervical metastatic lymph nodes from differentiated thyroid carcinoma or medullary thyroid carcinoma who meet the eligibility criteria and who have been determined to be an appropriate candidate for local ablation therapy will be offered enrollment into the study. Patients agreeing to participate will become subjects of the study if they read and sign an informed consent form. Treatment will be performed using three different ablation technologies (laser ablation, RFA or cryoablation) in a randomly assignment fashion. Subjects will have up to six simultaneous treated lesions larger than 0.8 cm diameter with positive fine-needle aspiration biopsy. Ultrasound (and CEUS when applicable) will be performed over 24 months follow up in order to evaluate efficacy. Baseline and follow-up data will be collected for each subject via a web-based electronic data collection tool. In case of recurrent disease treated by any ablative technique in patients who did not undergo previous neck dissection, a rescue neck dissection will be performed; in case of recurrent disease treated by any ablative technique in patients who underwent previous neck dissection, a new ablative technique approach will be considered.

Official Title
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Ultrasound Guided Percutaneous Thermal Ablation of Cervical Metastases From Thyroid Carcinoma

Conditions
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Thyroid Neoplasia, Well-Differentiated Thyroid Cancer, Medullary Thyroid Cancer, Lymph Node Metastases

Intervention / Treatment
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* Device: Laser ablation
* Device: Cryoablation
* Device: Radiofrequency ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Patients with fine needle aspiration biopsy (FNAb)-proven metastatic cervical lymph nodes at levels I, II, III, IV, V, VI or VII from differentiated thyroid carcinoma or medullary thyroid carcinoma who underwent total thyroidectomy and subsequent radioiodine therapy, in case of differentiated thyroid carcinoma. Patients considered high surgical risk candidate or patients who are informed about the ablation therapy and prefers it instead surgery; Patients with metastatic cervical lymph nodes over 0.8 cm diameter and under 4.0 cm diameter; no more than 6 simultaneous cervical nodal metastases; Cervical recurrences in previously lateral neck dissection patients for differentiated thyroid carcinoma or medullary thyroid carcinoma over 0.8 cm diameter. Exclusion Criteria: Age under 18 years Uncorrectable coagulopathy; Inconclusive or benign cytologic specimens; Pregnancy or breast-feeding; Anaplastic or poor-differentiated thyroid carcinoma; Partial thyroidectomy Cervical tumors not considered to surgery (invading vessels, nerves, larynx or trachea); Serious medical illness, including any of the following: uncontrolled angina, myocardial infarction, cerebrovascular event within 6 months prior to the baseline visit, uncontrolled congestive heart failure; Participation in other studies that could affect the primary endpoint

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: laser ablation<br>Percutaneous Laser Ablation for the treatment of metastatic cervical lymph nodes with > 0.8 cm diameter with biopsy-proven diagnosis of differentiated thyroid carcinoma or medullary thyroid carcinoma. | Device: Laser ablation<br>* Single session with Diode laser ablation system; one or two applicators will be used for treatments; one to three illuminations; fixed output power of 3 watts (W); pullback technique; delivered energy: 1200-1800 Joules (J) varying according to tumor volume; treatment under local anesthesia +- conscious or moderate sedation;<br>* Other names: LA;|
| Active Comparator: cryoablation<br>Percutaneous cryoablation for the treatment of metastatic cervical lymph nodes with > 0.8 cm diameter with biopsy-proven diagnosis of differentiated thyroid carcinoma or medullary thyroid carcinoma. | Device: Cryoablation<br>* Single session with Argon-based cryoablation system; one 17 Gauge (G) V-probe applicator will be used for treatments; fixed gas delivery of 100%; treatment under local anesthesia +- conscious or moderate sedation;<br>* Other names: Cryo;|
| Active Comparator: Radiofrequency ablation<br>Percutaneous radio frequency ablation for the treatment of metastatic cervical lymph nodes with > 0.8 cm diameter with biopsy-proven diagnosis of differentiated thyroid carcinoma or medullary thyroid carcinoma. | Device: Radiofrequency ablation<br>* Single session with radiofrequency generator; one 17 Gauge (G) V-tip applicator with a 1 to 4cm active tip; moving-shot technique or multiple overlapping shot technique with 60 Watts (W) output power; treatment under local anesthesia +- conscious or moderate sedation;<br>* Other names: RFA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of technical feasibility | defined as the ability to target the nodule and to perform ablation as preoperatively planned | immediately after the procedure | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of thermal ablation of thyroid carcinoma cervical lymph node metastases | Evaluation of minor and major complication rates, immediately after ablation; and one- and four-weeks post-ablation by telephone call. Minor and major complication rates [Designed as a safety issue: Yes]. The safety endpoint for this study is to assess the incidence and severity of procedure or device-related adverse events, as reported by the Common Terminology Criteria of Adverse Events - CTCAE V5. 2017 Version. | up to 4 weeks post-ablation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of technical success | Defined as the complete absence of color Doppler or, if applicable when tumors over 1.0 cm diameter, enhancement by contrast-enhanced ultrasound in the treated nodule | immediately after the procedure | 
| Evaluation of contrast-enhanced ultrasound pattern after thermal ablation therapy | Absence of enhancement is expected in treated cervical lymph nodes after local ablative therapy in comparison to pre-treatment enhancement pattern. Partial enhancement may indicate residual tumoral tissue requiring new ablation session | 12 months | 
| Evaluation of elastography pattern after thermal ablation therapy | Quantitative measurements of nodule stiffness designated by the most representative region of interest within the nodule estimating of Young's modulus in kilopascal (KPa) and shear wave velocity in centimetres per second (cm/s) of treated cervical lymph nodes after local ablative therapy in comparison to pre-treatment pattern. | 24 months | 
| Best response to the thermal ablation therapy | The best response is defined as a subject having local disease control related to lymph node volume reduction or volume stability in percentage will be assessed by ultrasound measurement in comparison to pre-treatment volume. | 24 months | 
| Evaluation of tumor marker response | Number of patients with tumor marker response: defined in negative thyroglobulin, calcitonin, or carcinoembryonic antigen (CEA) levels or anti-thyroglobulin antibodies | 24 months | 
| Evaluation of additional therapies | Number of patients with additional therapies: Additional therapies for persistent/recurrent local disease associated with the index tumor (s) under study or new cervical lymph node metastases. | 24 months | 
| Outcomes among thermal ablation therapies | Number of patients with complications, side effects and tolerability in each ablation technique. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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differentiated thyroid cancer, medullary thyroid cancer, cervical lymph nodes, contrast-enhanced ultrasound, thermal ablation, laser ablation, radiofrequency ablation, cryoablation, elastography