title: Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators.
abstract: BACKGROUND
  Pheochromocytomas and sympathetic paragangliomas are rare neuroendocrine tumors for which no precise histological or molecular markers have been identified to differentiate benign from malignant tumors.
  
  
  OBJECTIVE
  The aim was to determine whether primary tumor location and size are associated with malignancy and decreased survival.
  
  
  METHODS
  We performed a retrospective chart review of patients with either pheochromocytoma or sympathetic paraganglioma.
  
  
  METHODS
  The study group comprised 371 patients.
  
  
  METHODS
  Overall survival and disease-specific survival were analyzed according to tumor size and location.
  
  
  RESULTS
  Sixty percent of patients with sympathetic paragangliomas and 25% of patients with pheochromocytomas had metastatic disease. Metastasis was more commonly associated with primary tumors located in the mediastinum (69%) and the infradiaphragmatic paraaortic area, including the organ of Zuckerkandl (66%). The primary tumor was larger in patients with metastases than in patients without metastatic disease (P < 0.0001). Patients with sympathetic paragangliomas had a shorter overall survival than patients with pheochromocytomas (P < 0.0001); increased tumor size was associated with shorter overall survival (P < 0.001). Patients with sympathetic paragangliomas were twice as likely to die of disease than patients with pheochromocytomas (hazard ratio = 1.93; 95% confidence interval = 1.20-3.12; P = 0.007). As per multivariate analysis, the location of the primary tumor was a stronger predictor of metastases than was the size of the primary tumor.
  
  
  CONCLUSIONS
  The size and location of the primary tumor were significant clinical risk factors for metastasis and decreased overall survival duration. These findings delineate the follow-up and treatment for these tumors.
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, Unit 1461, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, Texas 77030, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Ayala-Ramirez
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Shamim
authors.initials: S
authors.lastname: Ejaz
authors.forename: Mouhammed Amir
authors.initials: MA
authors.lastname: Habra
authors.forename: Thereasa
authors.initials: T
authors.lastname: Rich
authors.forename: Naifa
authors.initials: N
authors.lastname: Busaidy
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Cote
authors.forename: Nancy
authors.initials: N
authors.lastname: Perrier
authors.forename: Alexandria
authors.initials: A
authors.lastname: Phan
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.forename: Steven
authors.initials: S
authors.lastname: Waguespack
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001342:Autonomic Nervous System Diseases / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002838:Chromaffin System / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D010235:Paraganglioma / Q000401:mortality / Q000473:pathology*; D010673:Pheochromocytoma / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D013534:Survival; D016019:Survival Analysis; D055815:Young Adult