Does Molecular Genotype Provide Useful Information in the Management of Radioiodine Refractory Thyroid Cancers? Results of a Retrospective Study

Target Oncol. 2016 Feb;11(1):71-82. doi: 10.1007/s11523-015-0380-y.


Introduction: Whether mutation status should be used to guide therapy is an important issue in many cancers. We correlated mutation profile in radioiodine-refractory (RAIR) metastatic thyroid cancers (TCs) with patient outcome and response to tyrosine kinase inhibitors (TKIs), and discussed the results with other published data.

Materials and methods: Outcome in 82 consecutive patients with metastatic RAIR thyroid carcinoma prospectively tested for BRAF, RAS and PI3KCA mutations was retrospectively analyzed, including 55 patients treated with multikinase inhibitors.

Results: Papillary thyroid carcinomas (PTCs) were the most frequent histological subtype (54.9 %), followed by poorly differentiated thyroid carcinoma [PDTC] (30.5 %) and follicular thyroid carcinoma [FTC] (14.6 %). A genetic mutation was identified in 23 patients (28 %) and BRAF was the most frequently mutated gene (23 %). Median progression-free survival (PFS) on first-line TKI treatment was 14.6 months (95% CI 9.9-18.4). BRAF mutation positively influenced median PFS, both in the entire TKI-treated cohort (median PFS 34.7 months versus 11.6 months; hazard ratio [HR] 0.29; 95% CI 0.09-0.98; p = 0.03) and in the TKI-treated PTC cohort (n = 22) [log-rank p = 0.086; HR 2.95; 95 % CI 0.81-10.70). However, in TKI-treated patients, PDTC histologic subtype was the only independent prognostic factor for PFS identified in the multivariate analysis (HR 2.36; 95% CI 1.01-5.54; p = 0.048).

Conclusion: Patients with BRAF-mutant PTC had a significantly longer PFS than BRAF wild-type when treated with TKIs. However, due to the small number of BRAF-mutant patients, further investigations are required, especially to understand the potential positive effect of BRAF mutations in RAIR TC patients while having a negative prognostic impact in RAI-sensitive PTC patients.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Carcinoma, Papillary / therapy
  • Disease Management
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Iodine Radioisotopes / adverse effects*
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Mutation / genetics*
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Radiation Tolerance
  • Retrospective Studies
  • Survival Rate
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / therapy


  • Biomarkers, Tumor
  • Iodine Radioisotopes