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 ¼ .001 and P ¼ .003, respectively). Clinical variables found to be predictive of post-B-Met survival on multivariate analysis included the presence of neurological symptoms (P ¼ .008) and extracranial metastases (P ¼ .04). Ulceration was the only primary tumor characteristic that remained a significant predictor of post-B-Met survival on multivariate analysis (P ¼ .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.

Malignant melanoma brain metastases: Treatment results and prognostic factors - a single-center retrospective study

“…Fife et al reported a median age at the time of diagnosis of brain metastasis of 49 and 57 years with a median time from initial diagnosis of melanoma until occurrence of cerebral metastasis of 2.5 and 3.7 years (10). In our study, patients were older when brain metastasis was confirmed (62 years), however, median time to development of cerebral metastasis (2.5 years in our patient group) was comparable with current literature (1.9-2.7 years) (17,18,37,39).…”

“…Predictors for OS in patients with malignant melanoma metastatic to the brain have been published previously and include Ldh levels, age, karnofsky index, number of brain metastasis, leptomeningeal spread, presence of extracerebral metastases, melanoma ulceration, histology and neurologic symptoms (10,13,18,25,37,(39)(40)(41)(42).…”

“…Few studies elucidated potential risk factors for the development of brain metastases in malignant melanoma including gender, Breslow thickness, ulceration, melanoma location, histological type, certain genetic alterations (i.e., BRAF mutation) and positive sentinel node (7,(17)(18)(19).…”

The effectiveness of brain metastases radiotherapy in patients with melanoma

“…In this case also the site's experience was compared with the results published by other authors [1,5,13,14,37,40,46]. Some investigators point to the adverse prognostics significance of the presence of metastases outside the brain, in particular in the lungs, liver, spleen and adrenal glands, and, to a lesser degree, in the bones, lymph nodes and skin [5,6,8,30,31,[33][34][35][40][41][42]. In the site's own material, in a single-variance analysis, it was shown that the co-existence of the metastases in extracranial locations was an adverse prognostic factor, which was, however, not confirmed by the results of the multivariance analysis.…”

Melanoma brain metastases presenting as delirium: a case report

“…Factors that have been shown to increase the risk for development of CNS metastasis in melanoma patients included male sex, thickness or ulceration of the skin lesion, primary site in the head and neck, mucosal or acral lentiginous tumors and nodular primary lesions 3 . Metastatic tumors often present with more neuropsychiatric symptoms 4 .…”