Add-on radioiodine during long-term BRAF/MEK inhibition in patients with RAI-refractory thyroid cancers: a reasonable option?

Endocrine. 2023 Sep;81(3):450-454. doi: 10.1007/s12020-023-03388-6. Epub 2023 May 16.

Abstract

Dual modulation of the MAPK pathway with BRAF (e.g., dabrafenib) and MEK (e.g., trametinib) inhibitors has the potential to re-establish radioiodine (RAI) sensitivity in BRAF-mutated RAI-refractory (RAI-R)-differentiated thyroid carcinoma (DTC) cells. Here we showed that (1) double BRAF/MEK inhibition may still reach a significant redifferentiation in patients with a long-history RAI-R DTC and multiple previous treatments; (2) the addition of high RAI activities may obtain a significant structural response in such patients; and (3) a divergence between increasing thyroglobulin and structural response may be a reliable biomarker or redifferentiation. Accordingly, the add-on prescription of high activities of 131I should be considered in RAI-R patients under multikinase inhibitors with stable or responding structural disease and divergent increase of Tg levels.

Keywords: Dedifferentiation; Differentiated thyroid carcinoma; Radioiodine; Radioiodine-refractory-differentiated thyroid carcinoma.

MeSH terms

  • Humans
  • Iodine Radioisotopes* / therapeutic use
  • Mitogen-Activated Protein Kinase Kinases
  • Proto-Oncogene Proteins B-raf / genetics
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / metabolism
  • Thyroid Neoplasms* / radiotherapy

Substances

  • Iodine-131
  • Iodine Radioisotopes
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinase Kinases
  • BRAF protein, human