Patient case: 46-year-old female with papillary thyroid carcinoma; genetic feature: NTRK1

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

Summary: 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.

Detailed description: 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.

Eligibility: Inclusion Criteria:
  -  R0 total thyroidectomy (in one or two stages, no residual disease present; Rx at the discretion of the MDT) 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:
  MDT decision for inclusion based on overall clinico-pathological assessment
  -  Papillary thyroid cancer
  -  Non aggressive histological features (small foci of aggressive histology allowed at the discretion of the MDT)
  -  pT1a(m): all individual foci ≤1cm
  -  pT1b and pT1b(m): >1-2cm
  -  pT2 and pT2(m): >2-4cm
  -  pT3 and pT3(m): >4cm
  -  pT3 R0: any size with minimal extrathyroidal extension recommended by the MDT
  -  pN0
  -  pN1a
  -  pNX
  -  Encapsulated follicular variant of papillary thyroid cancer (EFVPTC) with capsular invasion only
  -  Follicular thyroid cancer/ Hurthle cell cancer
  -  minimally invasive with capsular invasion only (or up to four foci of possible invasion of intra - capsular vessels at the discretion of the MDT only)
  -  pT1b: >1- 4 cm
  -  pT3 R0: (up to 4cm only) with minimal extrathyroidal extension recommended by the MDT
  -  Histological material available for Central Review
  -  Willing to use contraception for the duration of the trial until 6 months post radioiodine treatment (for females) or 4 months post treatment (for males), if allocated to the ablation group.
  N.B. Multifocal tumours (≥2 foci) of all histological types should be designated with "(m)", and the size of the largest focus determines the classification (as described in the TNM 7th edition). For example, if there are two foci, one 0.8cm and the other 3cm, the classification is based on the 3cm focus; i.e. pT2(m).
  Exclusion Criteria:
  -  pT1a - Papillary and Follicular carcinoma which is unifocal and ≤1cm in size
  -  <4cm Encapsulated Follicular Variant of Papillary Thyroid Cancer (EFVPTC) with no capsular invasion
  -  Anaplastic or medullary carcinoma
  -  R1/R2 Thyroidectomy
  -  Patients with:
  -  pN1b
  -  M1
  -  Aggressive Papillary thyroid cancer with any of the following features:
  -  Widely invasive
  -  Poorly differentiated
  -  Anaplastic
  -  Tall cell
  -  Columnar cell
  -  Diffuse sclerosing variants
  -  Follicular thyroid cancer/ Hürthle cell cancer with any of the following features:
  -  Anaplastic
  -  Widely invasive
  -  Poorly differentiated
  -  Tumours greater than 4cm
  -  Incomplete resection or lobectomy
  -  pT4 or macroscopic and microscopic tumour invasion of locoregional tissues or structures
  -  Pregnant women or women who are breast feeding
  -  Patients who have CT performed with iv contrast less than 2-3 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
  -  MDT decision against ablation or suitability for trail in the light of severe co-morbid condition/s:
  -  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

Relevance to patient case: not relevant