title: Feasibility of a randomized trial on adjuvant radio-iodine therapy in differentiated thyroid cancer.
abstract: BACKGROUND
  Justification for adjuvant radio-iodine (I-131) therapy in differentiated thyroid cancer (DTC) is purely based on retrospective data. This is true for ablative therapy and even more so for high-dosage adjuvant schedules. Randomized trials on the latter application are considered impossible due to anticipated formidable sample sizes required in a disease with an overall excellent prognosis like DTC.
  
  
  OBJECTIVE
  To develop and validate a model that could stratify for risk of recurrence, rather than survival, as is usually done in prognostic indices, and secondly, to use this model to estimate the sample size required for a randomized trial.
  
  
  METHODS
  From databases of three large Dutch centres, we identified 342 consecutive patients without known residual DTC after (near-) total thyroidectomy. Using Cox proportional hazards analysis, a model was validated that clearly distinguished risk categories of recurrence using commonly available baseline variables. The model included age, N stage at presentation and T stage in papillary carcinoma. According to this stratification, a subset of patients at substantial risk for relapse (30-40%) was identified. They could be eligible for a trial assessing the impact of high-dose adjuvant I-131 on recurrence rates. Assuming a clinically relevant effect of 30% reduction of relapses, 290 patients would have to be entered in either arm (alpha 0.05, power 80%).
  
  
  CONCLUSIONS
  We conclude that even though a randomized trial on this issue will be difficult to design and conduct, sample size is not the main problem.
authors.affiliation: Department of Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Dragoiescu
authors.forename: O S
authors.initials: OS
authors.lastname: Hoekstra
authors.forename: D J
authors.initials: DJ
authors.lastname: Kuik
authors.forename: P
authors.initials: P
authors.lastname: Lips
authors.forename: M A B D
authors.initials: MA
authors.lastname: Plaizier
authors.forename: P T R
authors.initials: PT
authors.lastname: Rodrigus
authors.forename: D A K C J M
authors.initials: DA
authors.lastname: Huijsmans
authors.forename: J G
authors.initials: JG
authors.lastname: Ribot
authors.forename: J
authors.initials: J
authors.lastname: Kuijpens
authors.forename: J W W
authors.initials: JW
authors.lastname: Coebergh
authors.forename: G J J
authors.initials: GJ
authors.lastname: Teule
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000532:radiotherapy* / Q000601:surgery*; D018265:Carcinoma, Papillary, Follicular / Q000532:radiotherapy / Q000601:surgery; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018401:Sample Size; D013964:Thyroid Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D013965:Thyroidectomy