A Prospective Evaluation of High Intensity Focused Ultrasound (HIFU) in the Treatment of Benign Thyroid Nodules
A Prospective Evaluation of High Intensity Focused Ultrasound (HIFU) in the Treatment of Benign Thyroid Nodules
To evaluate the short-term efficacy of high intensity focused ultrasound (HIFU) in the
 treatment of benign thyroid nodules
Background:

 Thyroid nodules are very common worldwide. In an iodine-replete population like Hong Kong,
 the estimated prevalence of a clinically palpable thyroid nodule, is close to 5% while the
 prevalence of ultrasonically detectable nodules could be up to 67%. With the frequent use of
 computed tomography, carotid ultrasound studies and positron emission scans nowadays, many
 small, non-palpable thyroid nodules are incidentally detected. The use of high intensity
 focused ultrasound MRI guided or ultrasound guided have been used to treat different types of
 soft tissue cancer like prostate cancer, liver cancer and breast cancer. This device has been
 tried in a clinical study where patients with thyroid nodules, who were already scheduled for
 thyroidectomy, were treated using HIFU in order to evaluate the safety and feasibility of the
 device and to better determine the treatment parameters and effect.

 The results showed that the overall safety of the treatment was satisfactory and the lesions
 produced by the HIFU shots in the nodule were precise. This pilot study was extended to a
 clinical trial where patients with a benign thyroid nodule were treated. Twenty-one patients
 were treated in this study versus 11 controls. No serious adverse events (SAE) have occurred.
 A patient with a toxic thyroid nodule was also treated with the HIFU device (Theraclion,
 France). The treatment was well tolerated and biologic euthyroidism was achieved at 3 months
 (TSH, 1.91 mIU/L) and was maintained at 6, 12, and 18 months. At 12 and 18 months, the
 treated nodule was barely seen as a nonvascularized hypoechoic scar. Thyroid scintigraphy
 showed a recovery of the thyroid iodine uptake.

 Since November 1st 2007, this HIFU device (Theraclion, France) has been CE marked for HIFU
 treatment of neck pathologies. 11 patients with primary hyperparathyroidism have been treated
 and followed. The mean follow-up is 9.5 months (1-28 months).

 Symptomatic hypocalcaemia was not observed in any patient after HIFU treatments or during
 follow-up. A prospective monocenter study was performed in Bulgaria for the treatment of
 benign solid thyroid nodule by US-Guided HIFU. Twenty thyroid nodules were treated during one
 HIFU session. The mean ± standard deviation nodule volume was 4.96 mL ± 2.79 at the start of
 the study. Nodule volume had decreased to 3.05 mL ±1.96 at the 3-month follow-up examination
 (n = 20, P < .001), and reached 2.91 mL ± 2.43 by the 6-month follow-up examination (n = 16,
 P < .001). By then, the mean volume reduction was 48.7% ± 24.3 (P< .001). Minor transient
 complications such as subcutaneous edema and mild skin redness were observed in two patients.
 Another monocenter study was performed in Germany in 2014. Ten patients with one thyroid
 nodule each were treated by HIFU. Three months after the procedure, thyroid nodule volume was
 significantly reduced by 48.8% (median) and a shrinkage up to 75% of the volume was observed.
 In terms of safety, no serious side effect related to the procedure was reported.

 Objectives:

 The present study is aimed to explore the followings:

 1. To evaluate the efficacy of the HIFU for the treatment of benign thyroid nodules using
 assessment of patient experience and adverse event reporting.

 2. To evaluate the tolerance of HIFU in the treatment of benign thyroid nodules.

 3. To determine the location parameters associated with optimal efficiency tissue ablation.

 The procedure schedule comprises:

 -  An first visit (V0)

 -  The HIFU session (D0)

 -  A visit at 1, 3 and 7 days after HIFU session (D1, D3, D7)

 -  A visit at 3 and 6 months (M3, M6).

 -  At each visit: any local and/or general adverse event will be documented in case report
 form (CRF).

 Ultrasound measurement of the treated nodule (in 3 dimensions) will be performed at each
 scheduled visit.

 The treatment procedure of Echopulse consists of five treatment steps:

 -  Pre-treatment ultrasonography

 -  Positioning

 -  Planning

 -  Generation of HIFU treatment pulses in the volume defined above; power setting is
 achieved on regularly spaced sites subsets.

 -  Post-treatment visualization and final report. The parameters of HIFU treatment will be
 part of the clinical study data base. When an HIFU session is prematurely interrupted,
 the reason of interruption will be recorded in the CRF (adverse event, technical
 failure, others).

 Study duration will lbe 6 months for each patient, counting from the post-HIFU day.
Inclusion Criteria:

 -  Male or female patient 18 years or older.

 -  Patient presenting with at least one thyroid nodule with no signs of malignancy:

 1. Non suspicious clinically and at ultrasonography imaging

 2. Benign cytological diagnosis at fine needle aspiration biopsy in the last 6
 months

 3. Normal serum calcitonin

 4. No history of neck irradiation

 -  Serum TSH and free T4 levels within the normal range

 -  Targeted nodule deemed to be accessible and eligible to HIFU

 -  Absence of vocal cord paresis at laryngoscopy

 -  Nodule greatest diameter between ≥10 - 20mm as measured by ultrasound

 -  Composition of the targeted nodule(s) : predominantly solid

 -  Patient is mentally competent and has given informed consent.

 Exclusion Criteria:

 -  Head and/or neck disease that prevents extension of neck

 -  Known history of thyroid cancer or other malignant tumors in the neck region

 -  History of neck irradiation

 -  Intranodular macrocalcification inducing a shadow in the thyroid significant enough to
 preclude HIFU treatment

 -  A nodule next to the posterior margin of the lobe with distance <15mm

 -  Pregnant or lactating woman

 -  Any contraindication to the assigned analgesia/anaesthesia.