Melanoma Brain Metastases: an Unmet Challenge in the Era of Active Therapy

Abstract

Metastatic disease to the brain is a frequent manifestation of melanoma and is associated with significant morbidity, mortality, and poor prognosis. Surgery and stereotactic radiosurgery provide local control but less frequently affect the overall outcome of melanoma brain metastases (MBM). The role of systemic therapies for active brain lesions has been largely under-investigated and those patients are excluded from the vast majority of clinical trials. The advent of active systemic therapy has revolutionized the care of melanoma patients but this benefit has not been systematically translated into intracranial activity. In this article, we review the biology and clinical outcomes of patients with MBM, the evidence supporting the use of radiation, surgery, and systemic therapy in MBM. Prospective studies that included patients with active MBM have shown clinical intracranial activity that parallels systemic activity and support the inclusion of patients with active MBM in clinical trials involving novel agents and combination therapies.

Metastatic melanoma of the gallbladder: report of two cases and a review of the literature

“…Distant metastatic sites include skin and soft tissues, lung, liver, brain and gastrointestinal tract [2][3][4][5]14]. Among the gastrointestinal metastases, the most common sites are small bowel (35-67 %), colon (9-15 %) and stomach (5-7 %) [6].…”

“…Although it accounts for\5 % of all skin cancers, melanoma is responsible for the majority of the skin-related deaths, due to its high tendency to metastasize. The most common sites of distant metastases are soft tissues (50-75 %), lung (70-87 %), liver (54-77 %), skin (50-75 %) and brain [2][3][4][5]. A small percentage of patients (from 2 to 4 %) affected by cutaneous melanoma are diagnosed with gastrointestinal metastases and the most common sites are small bowel, colon and stomach, with a low overall survival rate [6].…”

Outcomes in Melanoma Patients Treated with BRAF/MEK-Directed Therapy or Immune Checkpoint Inhibition Stratified by Clinical Trial versus Standard of Care

“…As MBM have historically been associated with worse prognosis [18] , we assessed survival based on metastatic sites. Across the entire study cohort, 64.5% ( n = 205) had only visceral metastases, 32.4% ( n = 103) had metastases of the CNS and viscera, and 3.1% ( n = 10) had only CNS metastases ( Table 1 ).…”

“…Furthermore, trial participants tend to be younger than the general oncology population [15,17] . These excluded or underrepresented groups comprise a significant portion of me lanoma morbidity; approximately 40-50% of stage IV melanoma patients eventually develop clinical manifestations of melanoma brain metastases (MBM), and 50-75% of melanoma patients have MBM at autopsy [18] . It has previously been demonstrated that metastatic melanoma patients receiving unrestricted access to ipilimumab through expanded access programs (EAPs), which included patients with ECOG PS >1 and active, untreated MBM, had worse mOS compared to patients on earlier clinical trials [19] .…”

Challenges in the Delivery of Therapies to Melanoma Brain Metastases

“…About 55% of all deaths in melanoma patients are due to the presence of MBM (Damsky et al 2014; Sloan et al 2009; Davies et al 2011; Zakrzewski et al 2011). Also, the presence of MBM in 55–75% of melanoma patients at autopsy indicates a severely unmet medical need (Gorantla et al 2013; McWilliams et al 2003). …”