HoT – A phase III randomised trial to compare the rates of cancer returning in patients with low-risk differentiated thyroid cancer after a hemithyroidectomy and total thyroidectomy

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-surgery-to-remove-the-whole-thyroid-or-part-of-the-thyroid-hot-trial (added 04/05/2022)

Background and study aims
The rate of well-differentiated thyroid cancer (DTC) is increasing faster than any other tumour. The current standard treatment for low-risk DTC is surgical removal of the whole thyroid gland called total thyroidectomy (TT), followed by radioiodine treatment. More recently, surgeons have started performing hemithyroidectomy (HT) (removal of the cancerous half of the thyroid) as international guidelines changed and studies suggested patients may benefit from less extensive surgery, whilst maintaining excellent cure rates. HT patients may not require life-long hormone replacement therapy, calcium and vitamin D supplements, and radioiodine treatment. However, results from these studies are biased and conflicting. There is uncertainty surrounding the most appropriate surgery causing variations in practice between different teams and hospitals.

HoT is the first trial to directly compare TT versus HT in terms of the rate of cancer returning, impact on quality of life, surgery-related side-effects, need for thyroid hormone replacement therapy after surgery, health resources use and cost-effectiveness to the NHS.

Who can participate?
Individuals aged 16 years or over with a diagnosis of low-risk differentiated thyroid cancer.

What does the study involve?
There will be two groups of patients entering the trial with the same diagnoses and prognosis (i.e. risk of cancer returning):
- Group 1: Patients who have already had a hemithyroidectomy for thyroid problems and are then subsequently diagnosed with low-risk DTC will be randomly assigned (50:50 chance) to receive regular surveillance (follow-up only) OR have a second operation to remove the rest of their thyroid gland (two-stage total thyroidectomy).
- Group 2: Patients diagnosed with low-risk DTC but not undergone surgery, will be randomly assigned (50:50 chance) to have either the whole thyroid gland removed (single-stage total thyroidectomy) or only part of the gland removed (a hemi-thyroidectomy).
All thyroid surgeries performed on the trial will be as per the standard of care at the treating hospital.
All patients on the trial will be followed up regularly for up to 6½ years. Patients will attend clinic visits for standard checks on their progress and health before surgery, sometime between 2 and 4 weeks after surgery, 6 months after surgery, then once a year for 6 years. These checks include clinical examinations, blood tests to check thyroid gland function and neck ultrasound scans. All patients will have an ultrasound scan of their neck every year. In several hospitals this scan is already part of routine care. For all patients, there is one extra ultrasound scan of their neck 6 months after surgery.
For research purposes patients will also be asked to complete four questionnaires about their health and well-being and a questionnaire to check voice function. Selected patients may be able to complete the questionnaires at home, using a web-based application (‘app’) that will send text (SMS) message alerts to their mobile phone/tablet. They can then complete these questionnaires on their mobile phone/tablet, rather than completing paper questionnaires at the hospital during clinic appointments. Using this ‘app’ is another part of the HoT trial, and is being done in partnership with an American company called Navio who own the ‘app’. This ‘app’ allows electronic collection of information from trial patients allowing us to see if this approach is better and easier for patients than if they used paper questionnaires.
The first 30-50 patients recruited to the HoT study will be asked to use the ‘app’. After this, patients will be randomly allocated (50:50 chance) to complete the well-being questionnaires either using the ‘app’ OR using paper forms. Patients who do not wish to take part in this study that evaluates the ‘app’ can instead use the paper version of the questionnaires throughout the trial or can switch from the web-based app to the paper questionnaires at any time if they wish.
After the initial 6½ years of follow-up long term follow up data on recurrences and mortality will be collected electronically from national registries and databases (e.g. NCRAS) for an additional 13 ½ years.
What are the possible benefits and risks of participating?

Patients will be treated as they would otherwise in routine care and receive the best treatment for their thyroid cancer whether they take part in this trial or not. By taking part in this trial, the patients will help us to understand more about treating patients, both in the UK and worldwide, with low-risk differentiated thyroid cancer and how best to treat them in the future. All patients taking part in the trial will have a neck ultrasound at their 6 month follow-up visit which may not always routinely be performed at all hospitals. Patients who have had a hemithyroidectomy before coming on to the trial and are then randomised to the surveillance arm will not need to have another surgery, avoiding the inconveniences of a second surgery along with the possible surgery-related complications. Patients who have a hemi-thyroidectomy as part of the trial may not need radioiodine ablation after (requires isolation in hospital) and may not need life-long thyroxine replacement therapy, which is likely to improve quality of life.

Both hemithyroidectomy and total-thyroidectomy procedures are performed routinely by surgeons as per standard of care and therefore do not pose any additional risks to patients beyond those associated with the surgeries. Both surgeries will be performed as per local site policy by qualified surgeons. A trial specific audit will be carried out on all recruiting hospitals to ensure both surgeries are being performed routinely there.

There is a small risk of the cancer recurring after both a hemithyroidectomy and a total thyroidectomy. Some studies have shown that the recurrence rate may be slightly higher in patients who have a hemithyroidectomy, however the difference was considered clinically small and overall survival was similar. Most recurrences happen within 3-5 years of initial treatment and whilst on the trial patients will be followed up annually for up to 6 and ½ years after the surgery with routine thyroglobulin measurements and neck ultrasound to check for signs of recurrence. Once trial follow-up visits end the patient will be followed up as per standard practice at their treating hospital. A risk assessment of the trial has been carried out and a site monitoring plan will be developed based on this to ensure the trial is being carried out according to the protocol and Good Clinical Practice.

Where is the study run from?
Cancer Research UK & UCL Cancer Trials Centre, London

When is the study starting and how long is it expected to run for?
August 2020 to July 2028

Who is funding the study?
National Institute for Health Research (NIHR) (UK) will fund the trial up to the 6 ½ years of follow-up. The additional 13 ½ years of long term follow-up data collection after will be funded by UCL CTC. The nested sub-study testing the clinical utility of Navio’s web-based app (software) will be funded by Navio and UCL CTC.

Who is the main contact?
ctc.hot@ucl.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• Scotland
• United Kingdom
• Wales

Study participating centres

Sponsor information

University College London
University/education

Joint Research Office
Gower Street
London
WC1E 6BT
England
United Kingdom

Phone	+44 2034 479995
Email	ctc.sponsor@ucl.ac.uk
Website	http://www.london.ac.uk/
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Government

Results and Publications

Study outputs

Editorial Notes

10/11/2023: The study contact was updated.
07/11/2023: The following changes were made:
1. ClinicalTrials.gov number added.
2. St James' University Hospital, Kings Cross Hospital, Kent and Canterbury Hospital, St Mary's Hospital, and Hull Royal Infirmary were removed as Study participating centres.
3. Ninewells Hospital, Luton and Dunstable University Hospital, Gstt @ Royal Devon and Exeter, Medway NHS Foundation Trust, Royal Derby Hospital, Aberdeen Royal Infirmary, Derriford Hospital, Northampton General Hospital, Forth Valley Royal Hospital and Ipswich Hospital were added as Study participating centres.
4. A link to patient information material was added.
04/05/2022: The Cancer Research UK plain English summary has been added.
10/08/2021: Trial's existence confirmed by the National Institute for Health Research (NIHR) (UK).