First-in-Human Clinical Feasibility Study of Ablation of Benign Thyroid Nodules Using Nanosecond Pulsed Field Ablation

<b><i>Background:</i></b> Thyroid nodules are common in the general population, and most are benign. Thyroidectomy remains the most common treatment for symptomatic benign thyroid nodular disease. The objective of this study is to determine if a novel, cell-specific, nonthermal modality called nanosecond pulsed field ablation (nsPFA) can provide a safe and effective treatment for symptomatic thyroid nodules. <b><i>Methods:</i></b> In this clinical feasibility trial (NCT06117085), an nsPFA percutaneous electrode was used to ablate benign thyroid nodules under ultrasound guidance. In Cohort 1 (5 patients), ablations were created during a thyroidectomy procedure (treat-and-resect), so that initial ablation zone characterization could be assessed histologically. In Cohort 2 (20 patients), up to 4 isolated ablations were created in the <i>in situ</i> thyroid for dose-ranging and to allow for estimation of ablation zone volume. In Cohort 3 (5 patients), the entire nodule was ablated with therapeutic intent using multiple, overlapping ablations for resolution of symptoms. <b><i>Results:</i></b> For Cohort 1, the mean ablation zone measured 1.7 cm long by 0.7 cm wide post-ablation. For Cohort 2, the mean ablation zone was estimated to be 2.7 cc in volume at 90 days post-ablation (based on nodule size reduction from baseline). Transient dysphonia (<24 hours) was seen in two patients treated at the highest ablation setting (93 mJ/mm²). For Cohort 3, treated nodules had a mean volume reduction of 48.2% as early as 2 weeks, and 71.1% at 1 month and 85.8% at 1 year. Patients could typically resume normal activities on the same day. There was no transient dysphonia in this group. Noticeable volume reduction and relief of symptoms were seen as early as 2 weeks post-treatment. No fibrosis or scars were seen on follow-up ultrasounds. No serious adverse events were reported for any cohorts. <b><i>Conclusions:</i></b> This first-in-human study supports the initial safety/efficacy profile of the nsPFA electrode system in treating benign thyroid nodules. The minimally invasive and nonthermal nature of nsPFA energy has the potential to reduce risk of major complications in treatment of benign thyroid nodules as compared with thyroidectomy or thermal ablation and to improve healing through rapid reduction ofablated areas and lack of postprocedural scarring.