title: Prognostic factors of disease-free survival after thyroidectomy in 170 young patients with a RET germline mutation: a multicenter study of the Groupe Francais d'Etude des Tumeurs Endocrines.
abstract: BACKGROUND
  In hereditary medullary thyroid carcinoma (HMTC), prophylactic surgery is the only curative option, which should be properly defined both in time and extent.
  
  
  OBJECTIVE
  To identify and characterize prognostic factors associated with disease-free survival (DFS) in children from HMTC families.
  
  
  METHODS
  We conducted a retrospective analysis of a multi-center cohort of 170 patients below age 21 at surgery. Demographic, clinical, genetic, biological data [basal and pentagastrine-stimulated calcitonin (CT and CT/Pg, respectively)], and tumor node metastasis (TNM) status were collected. DFS was assessed based on basal CT levels. Kaplan-Meier curves, Cox regression, and logistic regression models were used to determine factors associated with DFS and TNM staging.
  
  
  RESULTS
  No patients with a preoperative basal CT <31 ng/ml had persistent or recurrent disease. Medullary thyroid carcinoma defined by a diameter ≥10 mm [hazard ratio (HR): 6.0; 95% confidence interval (95% CI): 1.8-19.8] and N1 status (HR: 20.8; 95% CI: 3.9-109.8) were independently associated with DFS. Class D genotype [odds ratio (OR): 48.5, 95% CI: 10.6-225.1], preoperative basal CT >30 ng/liter (OR: 43.4, 95% CI: 5.2-359.8), and age >10 (OR: 5.5, 95% CI: 1.4-21.8) were associated with medullary thyroid carcinoma ≥10 mm. No patient with a preoperative basal CT <31 ng/ml had a N1 status. Class D genotype (OR: 48.6, 95% CI: 8.6-274.1), and age >10 (OR: 4.6, 95% CI: 1.1-19.0) were associated with N1 status.
  
  
  CONCLUSIONS
  In HMTC patients, DFS is best predicted by TNM staging and preoperative basal CT level below 30 pg/ml. Basal CT, class D genotype, and age constitute key determinants to decide preoperatively timely surgery.
authors.affiliation: Centre hospitalier universitaire Angers, Endocrinologie, Faculté de médecine, Université Angers, Angers 49933, France. virohmer@chu-angers.fr
authors.forename: V
authors.initials: V
authors.lastname: Rohmer
authors.forename: G
authors.initials: G
authors.lastname: Vidal-Trecan
authors.forename: A
authors.initials: A
authors.lastname: Bourdelot
authors.forename: P
authors.initials: P
authors.lastname: Niccoli
authors.forename: A
authors.initials: A
authors.lastname: Murat
authors.forename: J L
authors.initials: JL
authors.lastname: Wemeau
authors.forename: F
authors.initials: F
authors.lastname: Borson-Chazot
authors.forename: C
authors.initials: C
authors.lastname: Schvartz
authors.forename: A
authors.initials: A
authors.lastname: Tabarin
authors.forename: O
authors.initials: O
authors.lastname: Chabre
authors.forename: G
authors.initials: G
authors.lastname: Chabrier
authors.forename: P
authors.initials: P
authors.lastname: Caron
authors.forename: P
authors.initials: P
authors.lastname: Rodien
authors.forename: M
authors.initials: M
authors.lastname: Schlumberger
authors.forename: E
authors.initials: E
authors.lastname: Baudin
mesh_terms: D000293:Adolescent; D000328:Adult; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D017408:Guidelines as Topic; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D048631:Micronucleus, Germline; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D013965:Thyroidectomy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002116:Calcitonin; D004247:DNA; D051096:Proto-Oncogene Proteins c-ret