title: BRAF V600E status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence.
abstract: BACKGROUND
  Papillary thyroid cancer (PTC) recurrence risk is difficult to predict. No current risk classification system incorporates BRAF mutational status. Here, we assess the incremental value of BRAF mutational status in predicting PTC recurrence relative to existing recurrence risk algorithms.
  
  
  METHODS
  Serial data were collected for a historical cohort having undergone total thyroidectomy for papillary thyroid carcinoma (PTC) during a 5-year period. Corresponding BRAF(V600E) testing was performed and Cox proportional hazard regression modeling, with and without BRAF status, was used to evaluate existing recurrence risk algorithms.
  
  
  RESULTS
  The 5-year cumulative PTC recurrence incidence within our 356 patient cohort was 15%. A total of 205 (81%) of associated archived specimens were successfully genotyped, and 110 (54%) harbored the BRAF(V600E) mutation. The 5-year cumulative recurrence incidence among BRAF(V600E) patients was 20% versus 8% among BRAF wild type. BRAF(V600E) was significantly associated with time to recurrence when added to the following algorithms: AMES (hazard ratio [HR] 2.43 [confidence interval 1.08-5.49]), MACIS category (HR 2.46 [1.09-5.54]), AJCC-TNM (HR 2.51 [1.11-5.66]), and ATA recurrence-risk category (HR 2.44 [1.08-5.50]), and model discrimination improved (incremental c-index range 0.046-0.109).
  
  
  CONCLUSIONS
  The addition of BRAF mutational status to established risk algorithms improves the discrimination of risk recurrence in patients undergoing total thyroidectomy for PTC.
authors.affiliation: Endocrine Surgery Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-2696, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Prescott
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hodin
authors.forename: Long Phi
authors.initials: LP
authors.lastname: Le
authors.forename: Randall D
authors.initials: RD
authors.lastname: Gaz
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Randolph
authors.forename: Antonia E
authors.initials: AE
authors.lastname: Stephen
authors.forename: Sareh
authors.initials: S
authors.lastname: Parangi
authors.forename: Gilbert H
authors.initials: GH
authors.lastname: Daniels
authors.forename: Carrie C
authors.initials: CC
authors.lastname: Lubitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018570:Risk Assessment; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf