University of Pittsburgh Cancer Institute (UPCI)

Melanoma Brain Metastasis

BrainBrain metastasis is a common terminal pathway of melanoma progression and one of the largest opportunities for melanoma therapy development for which a number of investigations have been undertaken. Identifying and developing biomarkers of prognosis and of predictive utility may improve the therapeutic index for currently available agents approved for melanoma treatment, by enabling the application of therapies to patients who are most likely to respond.

Selected Publications

  • The prognosis of metastatic melanomas to the brain (MBM) is variable with prolonged survival in a subset. To study the biology of MBM, histopathologic analysis of tumor blocks from patients' craniotomy samples and whole-genome expression profiling (WGEP) with confirmatory immunohistochemistry were performed. High mononuclear infiltrate and low intratumoral hemorrhage were associated with prolonged overall survival (OS). Pathway analysis of WGEP data demonstrated that several immune-related BioCarta gene sets were associated with prolonged OS. WGEP analysis of MBM in comparison with same-patient extracranial metastases (EcM) and primary melanomas (PrM) showed that MBM and EcM were similar, but both differ significantly from PrM. Immunohistochemical analysis revealed that peritumoral CD3+ and CD8+ cells were associated with prolonged OS. (Hamilton et. al., Cancer. 2013 Aug 1;119(15):2737-46.)
  • Metastatic disease to the brain is a frequent manifestation of melanoma and is associated with significant morbidity and 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 underinvestigated, and patients with active brain lesions 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. The biology and clinical outcomes of patients with MBM, and the evidence supporting the use of radiation, surgery, and systemic therapy in MBM is reviewed. 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. (Gorantla et. al., Curr Oncol Rep. 2013 Oct;15(5):483-91.)
  • Brain metastases are common in patients with metastatic melanoma and median overall survival from their diagnosis is typically 17-22 weeks. Treatment with dabrafenib was assessed in patients with BRAF-mutant melanoma metastatic to the brain, and it was found that dabrafenib has activity and an acceptable safety profile in patients with Val600Glu BRAF-mutant melanoma and brain metastases irrespective of whether they are untreated or have been previously treated but have progressed. (Long et. al., Lancet Oncol. 2012 Nov;13(11):1087-95.)

Members

Karunamurthy, Arivarasan, MD
Pathology
Tarhini, Ahmad, MD, PhD
Medicine
Kirkwood, John, MD
Medicine