title: The presence of SDHB mutations should modify surgical indications for carotid body paragangliomas.
abstract: OBJECTIVE
  The aim of this study was to determine whether the genetic background of the disease should be incorporated into treatment decision making.
  
  
  BACKGROUND
  Carotid body paragangliomas are rare tumors that often affect patients with genetic mutations of the succinate dehydrogenase complex (SDHx). Despite growing evidence that germ line genetic mutations alter the aggressiveness of paragangliomas, treatment decisions are currently based only on clinical symptoms and tumor size in patients with carotid body paragangliomas.
  
  
  METHODS
  Retrospective analysis of 34 patients with carotid body paragangliomas who underwent genetic testing and surgical treatment. Recurrence was defined by the return of locoregional disease and/or development of distant metastases. Clinical characteristics and genetic testing results were analyzed as predictors of patient outcomes.
  
  
  RESULTS
  Thirty-four patients underwent 41 primary carotid body paraganglioma resections (median follow-up time of 42 months, range: 1-293). Overall survival was 91.2%. Twelve patients had germ line mutations in SDHB, 17 in SDHD, and 5 carried no known mutation. Surgical resection of larger tumors was associated with higher operative complications (odds ratio: 5.4, P = 0.05). Tumor size at resection was significantly smaller in patients with SDHB mutations than in patients with non-SDHB mutations (2.1 vs 3.3 cm, P = 0.02). Patients with a mutation in the SDHB gene also had significantly worse disease-free survival compared with patients without an SDHB gene mutation (P = 0.03).
  
  
  CONCLUSIONS
  Mutations in the SDHB gene are associated with worse disease-free survival after resection in patients with carotid body paragangliomas despite earlier intervention. This suggests that a more aggressive surgical approach is warranted in patients with SDHB mutations.
authors.affiliation: *Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD †Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and ‡Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Dhaval
authors.initials: D
authors.lastname: Patel
authors.forename: Tamara
authors.initials: T
authors.lastname: Prodanov
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002345:Carotid Body Tumor / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D002648:Child; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase