Differentiated Thyroid Cancer
Conditions
Brief summary
This is a multi-centre, randomised, non-inferiority, phase III study in patients with low risk differentiated thyroid cancer. Patients will be identified via oncology multidisciplinary team meetings. There will be two sources of patients in the trial, with the same histological diagnoses and prognosis (i.e. recurrence risk): * Group 1: Patients who have already had a HT for thyroid problems and are then subsequently diagnosed with low risk DTC will be randomised 1:1 to undergo surveillance only OR a second operation to remove the rest of their thyroid gland (two-stage total thyroidectomy). * Group 2: Patients diagnosed with low risk DTC using cytology (Thy5) but no surgery performed will be randomised 1:1 to have either a hemi-thyroidectomy OR a single-stage total thyroidectomy. The overall aim of the trial is to determine whether hemithyroidectomy is an acceptable and cost-effective surgical procedure compared to total thyroidectomy in low risk thyroid cancer. Overall, 456 patients will be recruited to the trial. Patients will be initially be followed up post-surgery then 12 monthly for 6 years.
Interventions
PROCEDURETotal Thyroidectomy
Total Thyroidectomy - surgical removal of entire thyroid gland
PROCEDUREHemithyroidectomy
Hemithyroidectomy - surgical removal of partial thyroid gland
Sponsors
University College, London
National Institute for Health Research, United Kingdom
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Group 1 (HT already performed prior to diagnosis) Inclusion criteria • Aged 16 or over Papillary thyroid cancer: * pT1b-2 (≤4cm) irrespective of molecular genetic markers * R0 resection (clinically excised but microscopic R1 resected tumours at discretion of the local MDT) * cN0 or pN0, pNX \& pN1a (≤5 foci, no extranodal spread) * Confined to thyroid or minimal extrathyroidal extension * No higher risk histological variants on morphology (small foci allowed at the discretion of the local MDT) * No angioinvasion NB. PTC is still eligible where microscopic invasion of endothelial lined small capillary vascular spaces and lymphatic channels are present. It becomes ineligible in the rare instances when there is definite invasion of a larger vascular structure such as a vein with smooth muscle in its wall. * Encapsulated FVPTC with capsular invasion only * Micro-PTC (≤1cm) * multifocal * unifocal with pN1a (≤5 foci; no extranodal spread) Follicular thyroid cancer (FTC), including oncocytic or Hürthle cell carcinoma: * pT1b-2 (≤4cm) irrespective of molecular genetic markers \- Minimally invasive, with capsular invasion +/- minimal (≤4 foci) vascular invasion (the latter is now called encapsulated angioinvasive and is at the discretion of the MDT) * Confined to thyroid or minimal extrathyroidal extension
Exclusion criteria
* \>4cm * unifocal pT1a (≤1cm) PTC or FTC (unless pN1a as above) * NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) * Anaplastic, poorly differentiated or medullary thyroid carcinoma * R2 * gross extrathyroidal extension * pT4 or macroscopic tumour invasion of loco-regional tissues or structures * pN1a with \>5 foci or extranodal spread * pN1b * M1 * Aggressive PTC with any of the following features: * Widely invasive * Poorly differentiated * Anaplastic * predominance of Tall cell, Columnar cell, Hobnail, Diffuse sclerosing and other higher risk variants * FTC, including oncocytic or Hürthle cell cancer with any of the following features: * Minimally invasive with extensive vascular invasion (now called encapsulated angioinvasive) (\>4 foci) * Widely invasive * Poorly differentiated * Anaplastic Group 2 (DTC on cytology or after core biopsy, who has not had prior thyroid surgery yet) Inclusion criteria * Aged 16 or over * 'low risk' differentiated thyroid cancer confirmed by cytology or core biopsy. * cT1b-2 irrespective of molecular genetic markers * cN0 * Contralateral lobe without suspicious nodule(s) (U2, or U3/U4 with Thy2 on FNAC)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3 Year Recurrence Rate | From surgery to any signs or symptoms of the cancer or death assessed up to a maximum of 3 years from surgery date | (defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first)) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 5 Year Recurrence Rate | From surgery to any signs or symptoms of the cancer or death assessed up to a maximum of 5 years from surgery date | (defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first)) |
| Anatomical Site of Recurrence | From surgery to confirmed recurrence assessed up to a maximum of 5 years from surgery date | Location of recurrence |
| Risk of Loco-Regional Recurrence | From surgery to confirmed recurrence assessed up to a maximum of 5 years from surgery date | (based on time to recurrence in the neck only) |
| Number of Additional Investigations and Procedures after Surgery | 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery | Number of further investigations/procedures related to the patient's thyroid surgery or thyroid cancer e.g. imaging, blood test, biopsy etc. |
| Type of Additional Investigations and Procedures after Surgery | 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery | Type of further investigations/procedures related to the patient's thyroid surgery or thyroid cancer e.g. imaging, blood test, biopsy etc. |
| Voice Function | Surgical complications and severity: From surgery date to discharge, 2-4 weeks, 6 months and 18 months from date of surgery; Voice Function: Post-randomisation/pre-surgery, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. | Measured using the Voice Handicap Index questionnaire (VHI-10); scores range from 0-40 with higher scores indicating greater voice-related handicap |
| Surgical complications and severity | Surgical complications and severity: From surgery date to discharge, 2-4 weeks, 6 months and 18 months from date of surgery; Voice Function: Post-randomisation/pre-surgery, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. | Using CTCAE v5.0 and the highest grade of each event type for each patient |
| Requirement for Hormone Replacement Therapy | From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. | (percentage of patients who require this therapy compared between the trial arms) |
| Health Related Quality of Life (EORTC QLQ-C30) | Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. | Measured using EORTC QLQ-C30; Scales range from 0-100 with higher scores for the functioning scales and global health status indicating higher QoL and higher scores on the symptom and single-item scales indicating lower QoL |
| Health Related Quality of Life (EORTC QLQ-THY35) | Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. | Measured using EORTC QLQ-THY35; Scales range from 0-100 with higher scores indicating higher QoL and lower scores indicating lower QoL |
| Health Related Quality of Life (EQ-5D-5L) | Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. | Measured using EQ-5D-5L; EQVAS score ranges from 0-100 with higher scores indicating higher QoL and lower scores indicating lower QoL; EQ-5D-5L index scores range from -0.224-1 with higher scores indicating higher QoL and lower scores indicating lower QoL |
| Health Related Quality of Life (FoP-Q-SF) | Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. | Measured using FoP-Q-SF; scores range from 12-60 with higher scores indicating lower QoL and lower scores indicating higher QoL |
| Cost and Health Resource Use (EQ-5D-5L) | a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery | Measured using EQ-5D-5L (generic QoL) |
| Cost and Health Resource Use (EORTC QLQ-C30) | a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery | Measured using EORTC QLQ-C30 (cancer-specific QoL) |
| Cost and Health Resource Use (EORTC QLQ-THY34) | a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery | Measured using EORTC QLQ-THY34 (Cancer site specific QoL) |
| Secondary Care Health Resource Use | a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery | Collected using eCRFs and retrospectively for the study period from data in the Hospital Episodes Statistics linked to records in the NCRAS |
| Primary Care Health Resource Use | a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery | Collected using eCRFs (Review of Primary Care Visits) |
Countries
United Kingdom
Contacts
CONTACTJeannie Chamberlain
PRINCIPAL_INVESTIGATORDae Kim
The Royal Marsden Hospital
Outcome results
None listed