IoN- Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients

• Phase II: monthly patient accrual rates [ Time Frame: Evaluated within months 7-18 of the trial ] [ Designated as safety issue: No ]
  To determine if recruitment into a phase III trial is feasible
• Phase III: 5-year disease-free survival (residual and recurrent) [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]

• Phase III: Cause Specific mortality [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]
• Phase III: Loco-regional recurrence [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]
  Both groups will be compared to ascertain if radio-iodine results in a statistically significant reduction in risk in developing loco-regional recurrence in the low risk subgroup of patients.
• Phase III: Distant metastases [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]
  Both groups will be compared to ascertain if radio-iodine results in a statistically significant reduction in risk in developing distant metastases in the low risk subgroup of patients.
• Phase III: Quality of Life [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]
• Phase III: Adverse events for all patients [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: Yes ]
  Adverse events will be collected for patients in both groups during treatment and the groups compared during analysis.
• Phase III: Incidence of second primary tumours [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]

• Phase III: Cause Specific mortality [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]
• Phase III: Loco-regional recurrence [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]
• Phase III: Distant metastases [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]
• Phase III: Quality of Life [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]
• Phase III: Adverse events [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: Yes ]
• Phase III: Incidence of second primary tumours [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ] [ Designated as safety issue: No ]

IoN is a phase II/ III trial that will look to ascertain whether or not radio-iodine ablation is necessary for low risk differentiated thyroid cancer patients.

Phase II: to determine if recruitment into a phase III trial is feasible, with a target of 10 patients per month during a minimum of 6 months (evaluated within months 7-18 of the trial).

Phase III: to determine whether the 5-year disease-free survival rate among patients who do not have routine Radioactive iodine (RAI) ablation is non-inferior to those who do.

• Active Comparator: Radioactive iodine (RAI) ablation Arm
  Patients will be randomised to receive Radioactive iodine (RAI) ablation 1.1 GBq I131
  Intervention: Radiation: I131 1.1 GBq
• No Intervention: No Radioactive iodine (No-RAI) ablation
  Patients will be randomised to receive No Radioactive iodine (No-RAI) ablation

Inclusion Criteria:

• R0 total thyroidectomy (in one or two stages, no residual disease present) within the last 6 months
• Negative pregnancy test in women of child bearing potential
• Aged 16 or over
• WHO performance status 0 - 2, self-caring
• Histological confirmation of differentiated thyroid carcinoma:

• Papillary thyroid cancer

  • Non aggressive histological features (small foci of aggressive histology allowed)
  • pT1b (1-2cm), intrathyroidal
  • pT2 (2-4cm), intrathyroidal
  • pT3, intrathyroidal only
  • Multifocal microcarcinoma
  • pN0
  • pN1a
  • pNX

• Follicular thyroid cancer/ Hürthle cell cancer (minimally invasive with capsular invasion only)

  • pT1b (1- 2cm), pT2 (2-4cm) intrathyroidal

Exclusion Criteria:

• Papillary and Follicular carcinoma which is unifocal and <1cm in size

• Encapsulated Follicular Variant of Papillary Thyroid Cancer (EFVPTC) that is:

  • non-invasive
  • angio invasive
• Anaplastic or medullary carcinoma
• R1 Thyroidectomy

• Patients with:

  • pN1b
  • M1

• Aggressive Papillary thyroid cancer with the following features:

  • Angio invasive
  • Widely invasive
  • Poorly differentiated
  • Anaplastic differentiation
  • Tall cell
  • Columnar cell
  • Diffuse sclerosing variants

• Follicular thyroid cancer/ Hürthle cell cancer with the following features:

  • Angio invasive
  • Widely invasive
  • Poorly differentiated
  • Tumours greater than 4cm
• Incomplete resection/ lobectomy
• Macroscopic and microscopic tumour invasion of locoregional tissues or structures
• Pregnant women or women who are lactating
• Patients who have CT performed with iv contrast less than 3 months before ablation
• Previous treatment for thyroid cancer (except surgery)
• Previous malignancies with limited life expectancy or likely to interfere with the patient's ability to be able to comply with treatment and/or follow-up at least for 5 years
• Dysphagia
• Oesophageal stricture
• Active gastritis
• Gastric erosions
• Peptic ulcer
• Suspected reduced gastrointestinal motility

• Severe co-morbid condition/s that would prevent ablation including:

  • Unstable angina
  • Recent myocardial infarction or cerebrovascular accident (CVA)
  • Severe labile hypertension

  • Any patient who cannot comply with radiation protection including:

    • patients with learning difficulties
    • patients with dementia
    • patients with a tracheostomy that require nursing care
    • patients requiring frequent nursing/ medical supervision