title: Redifferentiation of iodine-refractory BRAF V600E-mutant metastatic papillary thyroid cancer with dabrafenib.
abstract: OBJECTIVE
  To determine whether the selective BRAF inhibitor, dabrafenib, can stimulate radioiodine uptake in BRAF V600E-mutated unresectable or metastatic iodine-refractory papillary thyroid cancer (PTC).
  
  
  METHODS
  Ten patients with BRAF V600E-mutant iodine-refractory PTC were enrolled. Absence of radioiodine uptake on iodine-131 whole body scan obtained within 14 months of study entry was required. Each patient received dabrafenib (150 mg twice daily) for 25 days before thyrotropin α-stimulated iodine-131 whole body scan (4 mCi/148 MBq). Patients whose scan showed new sites of radioiodine uptake remained on dabrafenib for 17 more days, and then were treated with 150 mCi (5.5 GBq) iodine-131. The primary endpoint of the study was the percentage of patients with new radioiodine uptake after treatment with dabrafenib.
  
  
  RESULTS
  Six of 10 patients (60%) demonstrated new radioiodine uptake on whole body scan after treatment with dabrafenib. All 6 were treated with 5.5 GBq iodine-131. Two patients had partial responses and 4 patients had stable disease on standard radiographic restaging at 3 months. Thyroglobulin decreased in 4 of 6 treated patients. One patient developed squamous cell carcinoma of the skin. There were no other significant adverse events attributed to dabrafenib.
  
  
  CONCLUSIONS
  Dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory PTC, representing a potential new therapeutic approach for these patients.
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: S Michael
authors.initials: SM
authors.lastname: Rothenberg
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Thyroid Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: David G
authors.initials: DG
authors.lastname: McFadden
authors.affiliation: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Edwin L
authors.initials: EL
authors.lastname: Palmer
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Thyroid Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Gilbert H
authors.initials: GH
authors.lastname: Daniels
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. lwirth@mgh.harvard.edu.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Wirth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002291:Carcinoma, Papillary; D002454:Cell Differentiation / Q000235:genetics*; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D013954:Thyroglobulin / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D051598:Whole Body Imaging
chemical_list: D007093:Imidazoles; D007457:Iodine Radioisotopes; D010091:Oximes; D013954:Thyroglobulin; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib