Prognostic factors for survival in melanoma patients with brain metastases

Abstract

BACKGROUND:One of the most common and deadly complications of melanoma is brain metastases. The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS). METHODS: An institutional database of advanced melanoma patients enrolled on clinical trials in the Department of Melanoma Medical Oncology from 1986 to 2004 was reviewed and patients who developed brain metastases were identified. Date of diagnosis, patient age, pattern of brain involvement, timing relative to extracranial metastases, prior response to systemic therapy, and treatments given for brain metastases were assessed as potential prognostic factors for OS. RESULTS: Among 743 melanoma patients enrolled in clinical trials for regional or systemic metastatic disease, 330 (44%) patients developed brain metastases. The median OS after the diagnosis of brain metastases was 4.7 months. Diagnosis before 1996, increased number of parenchymal brain metastases, leptomeningeal involvement, and development of brain metastases after receiving systemic therapy for extracranial metastases were found to be significant prognostic factors for OS. Among patients who received systemic therapy as the initial treatment of brain metastases, patients who previously responded to systemic therapies had longer survival than patients who had not responded. CONCLUSIONS: The era, pattern, and timing of melanoma brain metastases were found to be strongly associated with survival. Previous responsiveness to systemic therapies did not predict better outcomes overall, but it did correlate with improved survival for patients with brain metastases who were treated with systemic therapies. These factors may be used in guiding patient management and for stratifying patients in clinical trials. Cancer 2011;117:1687-96.

Emerging findings into molecular mechanism of brain metastasis

“…Among metastatic breast cancer patients, approximately 10%‐16% patients develop symptomatic BM and another 10% patients are found to have asymptomatic brain involvement in postmortem 9. In addition, the melanoma which ranked third is calculated that more than half of patients with metastatic melanoma will develop BM since the rapidly changing systemic treatment in this disease 10. BM possesses distinct pathological patterns due to its different sources of tissues.…”

Clinicopathologic features associated with efficacy and long‐term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors

“…[6][7][8][9] The relative influence that these clinicopathologic factors and those known to be prognostic for early-stage melanoma (Breslow thickness of primary melanoma, ulceration, mitotic rate, and sex) 6,10 may have on MAPK inhibitor drug efficacy has not been studied formally in a multivariate model with adequate follow-up. Furthermore, longer term survival (>3 years) with MAPK inhibitors has not been reported, and there are limited data about the success of subsequent therapies in those progressing on MAPK inhibitors (particularly anti-programmed cell death 1 [PD-1] therapy).…”

Antidepressant use and risk of central nervous system metastasis

“…Patients diagnosed with leptomeningeal disease (LMD) have shorter survival times than those diagnosed with metastasis in the parenchyma [127,144].…”