Burden and Risk Factors of Brain Metastases in Melanoma: A Systematic Literature Review

Abstract

Melanoma can frequently metastasize to the brain with severe consequences. However, variation of melanoma brain metastases (MBM) development among populations is not well studied, and underlying mechanisms and risk factors for MBM development are not consistently documented. We conducted a systematic literature review (SLR) including a total of 39 articles to evaluate the proportion of melanoma patients who are diagnosed with, or develop, brain metastases, and summarize the risk factors of MBM. The average proportion of MBM was calculated and weighted by the sample size of each study. Meta-analyses were conducted for the selected risk factors using a random-effects model. The proportion of MBM at diagnosis was 33% (975 with MBM out of 2948 patients) among patients with cutaneous melanoma (excluding acral) and 23% (651/2875) among patients with cutaneous mixed with other types of melanoma. The proportion at diagnosis was lower among populations with mucosal (9/96, 9%) or uveal (4/184, 2%) melanoma and among populations outside the United States and Europe. Meta-analysis demonstrated that male vs. female gender and left-sided tumors vs. right-sided were significantly associated with increased risk of melanoma brain metastases. These data may help clinicians to assess an individual patient’s risk of developing melanoma brain metastases.

The Effect of Non-Overlapping Somatic Mutations in BRAF, NRAS, NF1, or CKIT on the Incidence and Outcome of Brain Metastases during Immune Checkpoint Inhibitor Therapy of Metastatic Melanoma

“…The percentage of metastatic melanoma patients who eventually develop brain metastases is highest in melanoma compared to other common cancers [2]. In the past, about 28-33% of metastatic melanoma patients were diagnosed with brain metastases at the time of diagnosis of metastatic disease [2,3]. An older trial randomized patients with metastatic melanoma (without brain metastases at enrollment) to either dacarbazine or temozolomide chemotherapy.…”

“…In fact, the incidence proportion percentage of melanoma patients who develop brain metastases is currently higher in melanoma than in all other cancers [2]. Historically, melanoma brain metastases (MBM) were identified in about 28-33% of patients at the time of metastatic disease diagnosis [2,3]. An additional 40-44% of patients without initial brain metastases developed MBM within 4 years of starting initial treatment [4,5].…”

Melanoma Brain Metastases: A Systematic Review of Opportunities for Earlier Detection, Diagnosis, and Treatment

“…Although MRI is not considered effective among patients with completely resected stage III melanoma prior to administering adjuvant treatment [ 52 ], an awareness of the risk factors aids in early detection. Currently, MBM is reported to favor left-side tumors with a significantly higher risk in males than females [ 53 ].…”

Prevention of Brain Metastases: A New Frontier

“…In terms of patient characteristics, male patients are nearly 1.5 times more likely than female patients to develop MBM which has been supported by numerous studies [121,133,134,145]. The cause of this difference is unknown.…”

“…Patients diagnosed with melanoma at any stage had a modest incidence portion of 0.65, but patients with metastatic disease only had a significant incidence portion of 28.16 [ 132 ]. Multiple additional studies consistently show that patients with stage IV melanoma are at a much higher risk for MBM than early-stage patients [ 128 , 129 , 133 , 134 ]. An autopsy study from 1978 of 216 patient with metastatic melanoma noted that 54% of patients had brain metastasis at the time of their death [ 135 ].…”