Is Ipilimumab effective in melanoma with limited brain metastasis treated with Gamma Knife procedure?

Keywords: melanoma, radiosurgery, gamma knife, outcome, immunotherapy

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     Brain metastasis in melanoma carries a poor prognosis with an overall survival of 3-5 months and minimal response to systemic therapy. Ipilimumab, a human IgG monoclonal antibody against CTLA-4, has shown to improve the survival in patients with metastatic non-CNS melanoma. Its ability to cross the blood brain barrier or as a radiation sensitizer is not clear at this time.
     The purpose of this study was to investigate the efficacy of Ipilimumab in the treatment of metastatic melanoma with limited brain metastases treated with Gamma Knife (GK).
     From 2008-2010, 55 patients with limited brain metastases from melanoma were treated with GK procedure.
     SRS was delivered to a median dose of 20 Gy delivered to 50% isodose line (Range15-20). The median number of lesions treated were 3 (Range 1-8). Ipilimumab was administered intravenously at 3mg/kg over 90 minutes every 3 weeks for a median of 4 doses (Range1-8) in 23 patients. Local control (LC), Progression free survival (PFS) and overall survival (OS) were assessed from the date of GK procedure.
     The median LC, PFS and OS for the entire group were 8, 6 and 5 months respectively. The cause of death was CNS progression in all but two patients. Salvage therapy was needed in 26 (47.3%) patients that included repeat GK in 20 and Whole Brain Radiotherapy in 7 patients. The 6 month LC, median PFS and median OS were 62.9%, 5 months and 6 months respectively in patients who received Ipilimumab and 62.6%, 7 months and 5 months respectively in patients who didn’t receive Ipilimumab ( p=ns). Intracranial hemorrhage was noted in 7 patients who received Ipilimumab compared to 9 in those who didn’t receive it (p=ns).
     This was a retrospective study.
     Administration of Ipilimumab does not appear to affect outcomes in patients with limited brain metastases who received GK procedure.
     Further experience will be necessary to determine the value of systemic therapies for patients with cerebral melanoma.


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