Clinicopathological characteristics at primary melanoma diagnosis as risk factors for brain metastasis

Abstract

Objective In order to better identify melanoma patients who are, at the time of primary melanoma diagnosis, at high risk of developing brain metastases, primary melanoma characteristics were examined as risk factors for brain metastasis development. Methods In a study of two patient cohorts, clinicopathological characteristics prospectively collected at primary cutaneous melanoma diagnosis for patients with/without brain metastasis were assessed in univariate and multivariate analyses using data from two prospectively-collected databases: Melanoma Cooperative Group (MCG) (1972–1982), and Interdisciplinary Melanoma Cooperative Group (IMCG) (2002–2009). Candidate risk factors were evaluated in association with time to brain metastasis via either the log-rank test or Cox proportional hazards regression analysis with/without considering competing risks. Results Out of 2341 total patients included in the study, 222 (9.5%) developed brain metastases (median follow-up: 98 months). The median time to brain metastases was 30.5 months, and the median survival time after brain metastases was 4 months. Increased hazard ratios (HR) for brain metastasis were found among thicker (logarithmic value in mm) (MCG – HR=1.97, P<0.0001; IMCG – HR=1.31, P=0.018), ulcerated (MCG –HR=1.93, P=0.01; IMCG – HR=3.14, P<0.0001), and advanced-stage (MCG – HR=2.08, P=0.008; IMCG – HR=2.56, P=0.0002) primary melanomas based on multivariate Cox regression analysis assuming the presence of competing risks. Conclusions Primary cutaneous melanoma thickness, ulceration, and stage were identified and validated as risk factors associated with time to melanoma brain metastasis.

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

“…Prior retrospective studies of melanoma patients with BM examined cohorts ranging in size from 49 to 670 patients [5,6,8-12]. The rate of BM in these cohorts was approximately 10% [5,6,8,9,11,13], which corresponds to the expected risk of developing BM after a diagnosis of primary cutaneous melanoma [2].…”

“…The rate of BM in these cohorts was approximately 10% [5,6,8,9,11,13], which corresponds to the expected risk of developing BM after a diagnosis of primary cutaneous melanoma [2]. Our cohort of 123 melanoma patients with BM represented just over 2% of patients in our melanoma database; this lower percentage likely reflects the composition of our database, which contains many patients with melanoma in situ.…”

“…Previous studies examining factors predictive of melanoma BM have shown an association with depth and ulceration of the primary tumor as well as location on the head and neck [5,8-10]. In this study, along with analyzing additional patient demographic and primary tumor factors that may be associated with the development of BM, our aim was to investigate the impact of BM detection setting (routine screening vs. symptomatic presentation) on clinical outcomes.…”

Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas

“…Another study by Baurain has shown the association of ulceration with clinical benefit of adjuvant vaccination with tumor-specific antigenic peptides in primary melanoma [41]. Ulceration has been known to be a histopathologic variable that portends increased metastatic risk [15, 42]. In this setting, ulceration may be more than a phenotype, but may in fact reflect, a more aggressive and immunogenic subtype of melanoma.…”

“…Work by Sarpa and colleagues demonstrated a significant relationship between the percentage of the tumor that is ulcerated and both sentinel lymph node status and OS; even minimal ulceration worsens the overall prognosis [14]. Moreover, ulceration, along with tumor thickness and disease stage, was shown to be one of the three risk factors most associated the development of brain metastasis [15]. …”