Title: Radiofrequency ABlation of Benign Intrathyroidal Tumours
Funder: Department of Health and Social Care

Abstract: Thyroid swelling is a common problem worldwide; over half of the population have thyroid nodules. The majority are benign (not cancerous) but can still cause problems with swallowing, breathing, and embarrassment due to their appearance. Until recently, an operation to remove all or part of the thyroid was the only treatment, the most common one being removing half of the gland, called hemithyroidectomy._x000D_ _x000D_ While thousands of hemithyroidectomies are performed each year, the operation is associated with certain risks. One of the most important problems is bruising or damage to the nerve that supplies the voice box, called the recurrent laryngeal nerve, which happens in around 10% of operations. This can lead to speaking and swallowing problems and may last a few weeks or months, or be permanent. Another problem is that in around a third of patients, the remaining half of the thyroid produces too little hormone (underactive thyroid) and the patient needs to take thyroid hormone replacement tablets (lifelong). For many patients, this is a significant problem and reduces their quality of life. There is no reliable way to predict in which patients their remaining thyroid lobe will become underactive._x000D_ _x000D_ A novel technique, radiofrequency ablation (RFA), has been approved by National Institute of Clinical Excellence as suitable for use in benign thyroid nodules. RFA does not involve an anaesthetic or an operation, and is performed with the aid of an ultrasound machine as a day-case procedure. RFA is used to shrink growths (or tumours) in various parts of the body, and in many studies has been shown to significantly shrink thyroid nodules and relieve the patient’s symptoms. In addition, these studies show that RFA is associated with a much lower complication rate than surgery, and has a much lower cost._x000D_ _x000D_ Unfortunately, no studies have conclusively shown that RFA works as well as surgery. Therefore many centres in the UK have been slow to adopt its use. This study aims to compare hemithyroidectomy with RFA in the treatment of benign thyroid nodules, to see if RFA is as good as surgery at reducing the symptoms patients feel, results in fewer complications and is cost effective. The study has been designed with patients, and will be a randomised trial to give the most conclusive answer possible. Patients that agree to take part will be randomly assigned to undergo either surgery or RFA, and at various times before and after the procedure will be asked to answer questions about the problems coming from their thyroid swelling and how this affects different aspects of their life. We will also assess how much the nodule has shrunk and if there are any side effects from RFA. By using this information, as well as information about how much their treatment has cost and the impact it has had on their life, we will be able to determine whether RFA is as good as surgery at treating people with benign thyroid nodules._x000D_ _x000D_ This trial is being conducted by the UK’s leading thyroid radiologists, surgeons and endocrinologists, as well as the highly experienced Birmingham Clinical Trials Unit. With the backing of the major professional bodies involved in thyroid disease and also the three main thyroid patient support groups in the UK, this represents a unique opportunity for a national multicentre trial that will have implications for the treatment of patients with thyroid nodules across the world.

Lay abstract: Research question:_x000D_ Is radiofrequency ablation (RFA) for benign thyroid nodules compared to conventional open surgery non-inferior for:_x000D_ 1 Patient symptom reduction_x000D_ 2 Cost effectiveness_x000D_ 3 Quality of life_x000D_ In addition, will RFA show reduced complication rates (hypothyroidism, recurrent laryngeal nerve injury)_x000D_ _x000D_ Background:_x000D_ Thyroid nodules are common, palpable in 5-7%, and evident on ultrasound in 50-60% of people. Their diagnostic pathway is well established and determines nodule function and its malignancy risk, stratifying those that require further treatment. Most thyroid nodules are benign and do not need treatment, but they may cause compressive symptoms. Historically, the therapy for compressive nodules is thyroid surgery. Recent percutaneous thermal ablative techniques are less invasive options. RFA is NICE-approved to treat benign thyroid nodules and clinical and cost-effectiveness evaluation has been recommended. Few randomised controlled trials have examined the efficacy of RFA versus standard surgery for symptom reduction, complications, cost effectiveness and acceptability._x000D_ _x000D_ Aims and objectives:_x000D_ To compare RFA and standard of care conventional hemithyroidectomy for symptom reduction and cost effectiveness._x000D_ _x000D_ Primary outcomes (12 months):_x000D_ 1 Goitre symptom score_x000D_ 2 Cost effectiveness_x000D_ _x000D_ Secondary outcomes:_x000D_ 1 Composite ThyPRO score_x000D_ 2 Complication rate/adverse events _x000D_ 3 Percentage volume reduction in treated nodule(s) at 12 months _x000D_ 4 Acceptability of RFA _x000D_ 5 Need for additional related procedures_x000D_ 6 Nodule recurrence_x000D_ 7 Pain intensity_x000D_ 8 Related re-admission within 30 days of procedure_x000D_ _x000D_ Methods:_x000D_ Pragmatic multicentre randomised non-inferiority trial with 1:1 randomisation to compare hemithyroidectomy with RFA. Patients will be >18 years, euthyroid, with evidence of compression or cosmetic symptoms from their benign thyroid nodule(s). Symptoms will be assessed through the ThyPro questionnaire goitre domain. A comprehensive training programme will be provided to accredit UK thyroid radiologists in thyroid RFA, in 20-30 UK centres. _x000D_ _x000D_ Patients will be followed with thyroid function and vocal cord checks at appropriate intervals. Nodule volume, symptoms, quality of life, pain intensity and health economic data will be collected during 3 years follow-up. _x000D_ _x000D_ We will recruit 224 patients in both RFA and surgery groups to determine if RFA is inferior to surgery. Totally 448 patients will be recruited from 20-30 UK centres (2 patients/centre/ month). Analysis will be on intention to treat basis and health economic evaluation of relative cost-effectiveness of RFA compared with surgery._x000D_ _x000D_ Timelines for delivery:_x000D_ 0-6 months: approval_x000D_ 7-16 months: set up and training _x000D_ 7-23 months: recruitment_x000D_ 24-59 months: follow-up_x000D_ 60-65 months: analysis/write-up_x000D_ _x000D_ Anticipated impact and dissemination:_x000D_ If RFA is equivalent to surgery for symptom reduction and more cost effective, and, secondarily, at least equivalent or better for complications, this will promote the wide use of RFA across the UK for benign thyroid disease, serve patients better and be cost-efficient._x000D_ _x000D_ Effective communication of results will be through presentation at clinician and patient events, high impact publications, webinars, newsletters and social media. The trial is an exemplar of close collaboration between endocrinologists, surgeons and radiologists strengthened by longstanding close links with thyroid disease patient-led groups.

Research activity codes: 6.4 SURGERY
Health categories: METABOLIC AND ENDOCRINE