title: Second primary malignancy risk after radioactive iodine treatment for thyroid cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  The risk of second primary malignancies (SPMs) associated with cancer therapies is an important concern of thyroid cancer survivors and physicians. Our objective was to determine if the risk of SPMs is increased in individuals with thyroid cancer treated with radioactive iodine (RAI), compared to those not treated with RAI.
  
  
  METHODS
  We performed a systematic review of the literature and meta-analysis. Two independent reviewers screened citations and reviewed full-text papers. If not reported by the primary authors, the relative risk (RR) of SPMs was calculated by dividing the standardized incidence ratio of SPM in individuals with thyroid cancer treated with RAI compared to those not treated with RAI (with associated 95% confidence intervals [CI]). The natural logarithms of RRs of respective SPMs, weighted by the inverse of the variance, were pooled using fixed effects models and the exponential of the results was reported.
  
  
  RESULTS
  Two multi-center studies (one from Europe and the other from North America) were included in this review. The RR of SPMs in thyroid cancer survivors treated with RAI was significantly increased at 1.19 (95% confidence interval [CI] 1.04, 1.36, p = 0.010), relative to thyroid cancer survivors not treated with RAI (data from 16,502 individuals), using a minimum latency period of 2 to 3 years after thyroid cancer diagnosis. The RR of leukemia was also significantly increased in thyroid cancer survivors treated with RAI, with an RR of 2.5 (95% CI 1.13, 5.53, p = 0.024). We did not observe a significantly increased risk of the following cancers related to prior RAI treatment: bladder, breast, central nervous system, colon and rectum, digestive tract, stomach, pancreas, kidney (and renal pelvis), lung, or melanoma of skin.
  
  
  CONCLUSIONS
  The risk of SPMs in thyroid cancer survivors treated with RAI is slightly increased compared to thyroid cancer survivors not treated with RAI.
authors.affiliation: Division of Endocrinology and Department of Medicine, University Health Network, Toronto, Ontario, Canada. sawkaam@yahoo.com
authors.forename: Anna M
authors.initials: AM
authors.lastname: Sawka
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.forename: Luciana
authors.initials: L
authors.lastname: Parlea
authors.forename: Irada
authors.initials: I
authors.lastname: Ibrahim-Zada
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsang
authors.forename: James D
authors.initials: JD
authors.lastname: Brierley
authors.forename: Sharon
authors.initials: S
authors.lastname: Straus
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
authors.forename: David P
authors.initials: DP
authors.lastname: Goldstein
mesh_terms: D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D007953:Leukemia, Radiation-Induced / Q000209:etiology; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D018570:Risk Assessment; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000532:radiotherapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007457:Iodine Radioisotopes