title: Extended Antitumor Response of a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib.
abstract: BACKGROUND
  For patients with metastatic papillary thyroid carcinoma (PTC) refractory to radioactive iodine (RAI) treatment, systemic chemotherapy has limited efficacy. Such tumors frequently harbor BRAF V600E, and this alteration may predict responsiveness to vemurafenib treatment.
  
  
  OBJECTIVE
  We report a metastatic PTC patient refractory to RAI treatment that underwent genomic profiling by next-generation sequencing. The sole genomic alteration identified was BRAF V600E on a near diploid genome with trisomy 1q. With vemurafenib treatment, the patient experienced a dramatic radiographic and clinical improvement, with the duration of an ongoing antitumor response exceeding 23 months.
  
  
  METHODS
  Hybridization capture of 3,769 exons of 236 cancer-related genes and the introns of 19 genes frequently rearranged in cancer was applied to >50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of a lymph node containing metastatic PTC and was sequenced to a high, uniform coverage of ×616.
  
  
  RESULTS
  A BRAF V600E alteration was identified with no other somatic genomic alterations present within a near diploid tumor genome. The patient initially received vemurafenib at 960 mg twice daily that was reduced to 480 mg twice daily due to rash and diarrhea and has experienced an ongoing antitumor response exceeding 23 months by both PET-CT and dedicated CT imaging.
  
  
  CONCLUSIONS
  Genomic profiling in metastatic, RAI-refractory PTC can reveal a targetable BRAF V600E alteration without compounding somatic alterations, and such patients may derive a more prolonged benefit from vemurafenib treatment. Prospective clinical trials are ongoing to confirm our preliminary observation.
authors.affiliation: Foundation Medicine, Inc., Cambridge, Mass., USA.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Foundation Medicine, Inc., Cambridge, Mass., USA.
authors.forename: Je
authors.initials: J
authors.lastname: He
authors.affiliation: Willamette Valley Cancer Institute, Eugene, Oreg., USA.
authors.forename: Wade
authors.initials: W
authors.lastname: Carson
authors.affiliation: Foundation Medicine, Inc., Cambridge, Mass., USA.
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Willamette Valley Cancer Institute, Eugene, Oreg., USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fiorillo
authors.affiliation: Foundation Medicine, Inc., Cambridge, Mass., USA.
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
authors.affiliation: Foundation Medicine, Inc., Cambridge, Mass., USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Palmer
authors.affiliation: Foundation Medicine, Inc., Cambridge, Mass., USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Foundation Medicine, Inc., Cambridge, Mass., USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Willamette Valley Cancer Institute, Eugene, Oreg., USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sharman
keywords: BRAF V600E; Papillary thyroid carcinoma; Vemurafenib