Second primary malignancies induced by radioactive iodine treatment of differentiated thyroid carcinoma — a critical review and evaluation of the existing evidence

Maximilian J. Reinecke, Gerrit Ahlers, Andreas Burchert, Friederike Eilsberger, Glenn D. Flux, Robert J. Marlowe, Hans Helge Mueller, Christoph Reiners, Fenja Rohde, Hanneke M. van Santen, Markus Luster

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Purpose: Concern is growing about long-term side effects of differentiated thyroid cancer treatment, most notably radioactive iodine (RAI) therapy. However, published studies on the subject have had heterogeneous cohorts and conflicting results. This review seeks to provide an updated evaluation of published evidence, and to elucidate the risk of second primary malignancies (SPMs), especially secondary hematologic malignancies (SHMs), attributable to RAI therapy. Methods: An extensive literature search was performed in Ovid MEDLINE, Ovid MEDLINE and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Epub Ahead of Print, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed. Studies regarding RAI-induced SPMs or a dose–response relationship between RAI therapy and SPMs were identified, 10 of which were eligible for the analysis. We evaluated risk of bias in each study and judged quality of evidence (QOE) across all studies using the Grading of Recommendations, Assessment, Development and Evaluations approach. Results: For the outcome “SPM”, the relative effect (relative risk, hazard ratio, or odds ratio) of RAI vs. no RAI ranged from 1.14 to 1.84 across studies, but most results were not statistically significant. For the outcome “SHM”, reported relative effects ranged from 1.30 to 2.50, with 2/3 of the studies presenting statistically significant results. In 7/8 of the studies, increased risk for SPM was shown with increasing cumulative RAI activity. QOE was “very low” regarding SPM after RAI and regarding a dose–response relationship, and “low” for SHM after RAI. Conclusion: Based on low quality evidence, an excess risk for the development of SPM cannot be excluded but is expected to be small.

Original languageEnglish
Pages (from-to)3247-3256
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume49
Issue number9
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Differentiated thyroid carcinoma
  • Dose–response relationship
  • Effect of dose on second primary malignancy risk
  • Hematologic malignancy
  • Radioiodine therapy
  • Second primary malignancy
  • Adenocarcinoma/complications
  • Humans
  • Risk
  • Neoplasms, Second Primary/etiology
  • Iodine Radioisotopes/adverse effects
  • Thyroid Neoplasms/radiotherapy
  • Neoplasms, Radiation-Induced/etiology

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