title: Clinical variables and primary tumor characteristics predictive of the development of melanoma brain metastases and post-brain metastases survival.
abstract: BACKGROUND
  Melanoma patients who develop brain metastases (B-Met) have limited survival and are excluded from most clinical trials. In the current study, the authors attempted to identify primary tumor characteristics and clinical features predictive of B-Met development and post-B-Met survival.
  
  
  METHODS
  A prospectively accrued cohort of 900 melanoma patients was studied to identify clinicopathologic features of primary melanoma (eg, thickness, ulceration, mitotic index, and lymphovascular invasion) that are predictive of B-Met development and survival after a diagnosis of B-Met. Associations between clinical variables present at the time of B-Met diagnosis (eg, extracranial metastases, B-Met location, and the presence of neurological symptoms) and post-B-Met survival were also assessed. Univariate associations were analyzed using Kaplan-Meier survival analysis, and the effect of independent predictors was assessed using multivariate Cox proportional hazards regression analysis.
  
  
  RESULTS
  Of the 900 melanoma patients studied, 89 (10%) developed B-Met. Ulceration and site of the primary tumor on the head and neck were found to be independent predictors of B-Met development on multivariate analysis (P = .001 and P = .003, respectively). Clinical variables found to be predictive of post-B-Met survival on multivariate analysis included the presence of neurological symptoms (P = .008) and extracranial metastases (P = .04). Ulceration was the only primary tumor characteristic that remained a significant predictor of post-B-Met survival on multivariate analysis (P = .04).
  
  
  CONCLUSIONS
  Primary tumor ulceration was found to be the strongest predictor of B-Met development and remained an independent predictor of decreased post-B-Met survival in a multivariate analysis inclusive of primary tumor characteristics and clinical variables. The results of the current study suggest that patients with ulcerated primary tumors should be prospectively studied to determine whether heightened surveillance for B-Met can improve clinical outcome.
authors.affiliation: The New York University Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine and New York University Cancer Institute, New York, New York, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Zakrzewski
authors.forename: Laurel N
authors.initials: LN
authors.lastname: Geraghty
authors.forename: Amy E
authors.initials: AE
authors.lastname: Rose
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: David
authors.initials: D
authors.lastname: Polsky
authors.forename: Richard
authors.initials: R
authors.lastname: Shapiro
authors.forename: Russell
authors.initials: R
authors.lastname: Berman
authors.forename: Farbod
authors.initials: F
authors.lastname: Darvishian
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
authors.forename: Anna
authors.initials: A
authors.lastname: Pavlick
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
mesh_terms: D000367:Age Factors; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality* / Q000473:pathology / Q000556:secondary*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000473:pathology; D016019:Survival Analysis