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

Abstract

Objective Melanoma metastasis to the brain is associated with poor prognosis. We sought to determine patient demographics and primary tumor factors associated with development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. Methods A database of melanoma patients seen from 1999-2015 at our institution was reviewed to identify patients that developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. Results 123 patients with BM were matched by initial presenting stage to 237 patients without BM. Characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020) and Breslow depth >4mm (P=0.048), while location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, p=0.007) than non-scalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in clinical outcomes between patients whose BM were detected upon routine screening vs. upon symptomatic presentation. Conclusions Factors predictive of developing BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type and ulceration, but not detection setting, were associated with worse clinical outcomes.

Is cancer biology different in older patients?

“…139,140 Therefore, it is not surprising that older patients preferentially develop primary melanoma in habitually sun-exposed areas, such as the head and neck, face, and dorsal-distal side of the extremities. 126,128,131 Notably, several studies indicate that melanoma located on the scalp is associated with a higher incidence of brain metastases 141,142 and represents an independent predictor for worse melanoma-specific survival. 143,144 When comparing the distribution of the histopathological subtypes in different age groups, it is notable that nodular melanoma, an aggressive subtype with a disproportionally high case-fatality rate compared with the incidence rate, 145 is more frequent in the older patient.…”

Deciphering mechanisms of brain metastasis in melanoma - the gist of the matter

“…In addition, the time to development or detection of melanoma brain metastases ranges from < 1 year to > 5 years [ 6 ] with a median time of 2.5 years (30.5 months) [ 7 ]. Several risk factors have been identified, including the thickness (Breslow depth > 3 mm [ 8 ]), ulceration [ 7 ] and the location of the primary melanoma [ 9 ].…”

Nonsurgical Management of Melanoma Brain Metastasis: Current Therapeutics, Challenges, and Strategies for Progress

“…These include the Breslow thickness (more than 4 mm), primary site of disease, nodular histology, stage, and, recently, mitotic rate, mutations in the BRAF/NRAS pathway, PI3K/AKT activation, and loss of PTEN. [3][4][5][6][7] In advanced melanoma, M1b or M1c disease at diagnosis is associated with a significant increase in the development of CNS metastasis (p , .0001; HR, 2.643 and 2.127, respectively) compared with M1a or stage III disease. 8 Incidence of CNS disease is also increased, with primaries arising in the head and neck (6.7%) more than in the trunk/limb (4.7%; p = .003).…”