Cryoablation and RFA of Benign Thyroid Nodules: Pilot Study

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 cryoablation and a radiofrequency ablation in the treatment of benign thyroid nodules as an alternative to the surgery. Ablation of benign thyroid nodules with cryoablation will be directed to patients with benign thyroid lesions (two benign cytological examinations) measuring between 5 and 65 mL of volume and less than 40% of cystic component; patients must present with serum free thyroxine (T4) and thyroid stimulating hormone (TSH) between the normal range values, with no signs of thyroiditis by serum antibodies over 100% of the standard values; calcitonin levels in the normal range values. The cryoablation or RFA will be directed in a non-randomized fashion. Clinical, laboratorial and imaging monitoring will be performed in 12 months, including contrast-enhanced ultrasound when indicated, by 1, 3, 6 and 12 months.

Detailed Description
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Palpable nodular thyroid disease is common in up to 6.4% of the population, and it becomes more common when the thyroid is examined by ultrasound. The vast majority of nodules are benign and, over time, do not change considerably in size. The main treatment indications for a euthyroid patient with a benign thyroid nodule that is not hyperfunctioning are compression of the trachea or esophagus, growth of the nodule, and recurrence of a cystic nodule after aspiration. Other indications for treatment are neck discomfort, cosmetic concern, and patient anxiety about the lump. The main therapeutic options are surgery (unilateral lobectomy) and treatment with thyroxine. Thermal ablative therapy has become a treatment option for solid thyroid lesions, with extensive reports in the medical literature on safety and efficacy with laser and radiofrequency devices, including long-term follow-up studies (10 years). In our country, several radiofrequency thermal ablation (RFA) devices are available for use in the treatment of benign thyroid nodules, although some ablation devices do not have the manufacturer's registration for this purpose. Additionally, there is no record in the medical literature of the use of cryoablation devices for the ablation of benign thyroid nodules, although they are used for the treatment of tumor lesions in different sites (hepatic, renal, pulmonary, bone and cervical lymph nodes).The objective of this research is to evaluate, in a pilot study, the safety and efficacy of cryoablation in the treatment of benign thyroid nodules. Additionally, the same evaluation is possible using an RFA device not yet tested for this purpose.

Official Title
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Thermal Ablation of Benign Thyroid Nodules With Cryoablation or Radiofrequency

Conditions
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Benign Thyroid Nodule

Intervention / Treatment
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* 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 solitary or dominant nodules with two consecutive fine needle aspiration biopsy (FNAb)-proven benign in the last 12 months Thyroid nodules should be solid or almost solid (less than 40% of liquid component) with volume between 5 and 65 cc; Patients considered high surgical risk candidates or patients are eligible to surgery who are informed about the ablation therapy and prefers it instead surgery; Calcitonin, thyroglobulin or TSH serum levels in the normal range values No thyroid autoimmune signs on ultrasound or by autoantibody levels above 100% of the standard levels Exclusion Criteria: Age under 18 years Extensive goiter Predominantly cystic nodule with small solid remnant (less than 10%) Hyperfunctioning nodules (confirmed by scintigraphy) Nodule volume > 65 cc TSH levels above the normal range Auto-immune treatment / thyroiditis Uncorrectable coagulopathy / impossibility to interrupt anticoagulants; Malignant or suspected malignant cytologic specimens; Pregnancy or breast-feeding; Anaplastic or poor-differentiated thyroid carcinoma; Partial thyroidectomy Asymptomatic patients

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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cryoablation<br>Device: Cryoablation Single session with an argon-based device; a V-probe 17-G applicator will be used for the treatments; gas release 100%; local anesthesia or moderate sedation or general anesthesia at discretion of the anesthesiology / interventional radiology team; benign thyroid nodules (two benign cytological examinations) measuring between 5 and 65 mL of volume and less than 40% of cystic component; | Device: cryoablation<br>* Single session with an argon-based cryoablation device; an specific applicator will be used for the treatments; gas release 100% for cryoablation; local anesthesia or moderate sedation or general anesthesia at discretion of the anesthesiology / interventional radiology team; benign thyroid nodules (two benign cytological examinations) measuring between 5 and 65 mL of volume and less than 40% of cystic component;<br>|
| Experimental: Radiofrequency<br>Single session with an RF device; an antenna will be used for the treatments; local anesthesia or moderate sedation or general anesthesia at discretion of the anesthesiology / interventional radiology team; benign thyroid nodules (two benign cytological examinations) measuring between 5 and 65 mL of volume and less than 40% of cystic component; | Device: radiofrequency ablation<br>* Single session with a radio frequency ablation device; an specific applicator will be used for the treatments; high impedance rates for RFA with moving-shot technique; local anesthesia or moderate sedation or general anesthesia at discretion of the anesthesiology / interventional radiology team; benign thyroid nodules (two benign cytological examinations) measuring between 5 and 65 mL of volume and less than 40% of cystic component;<br>|

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 puncture the nodule and perform the ablation as preoperatively planned. | immediately after ablation | 
| 2) Incidence of adverse events secondary to the treatment (safety and tolerability) of thermal ablation of benign thyroid nodules | Evaluation of minor and major complication rates, immediately after and 1 month after ablation [designed as a safety measure: yes]. The safety endpoint for this study is to evaluate the incidence and severity of the procedure or device-related adverse events, as reported by the CTCAE V5.2017. | up to 4 weeks after ablation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of technical success | Technical success is defined as to achieve a nodular volume ablation of 50% at 12-month follow up compared to baseline. Nodule volume measurement is performed with the ellipsoid formula: length x width x depth x 0.524. | ultrasound examinations 1, 3, 6 and 12 months after ablation |