title: Ipilimumab and whole brain radiation therapy for melanoma brain metastases.
abstract: Brain metastases (BM) frequently develop in patients with melanoma and are associated with a poor prognosis. Whole brain radiation therapy (WBRT) is a standard intervention for intracranial disease, particularly in patients with multiple BM. Ipilimumab improves survival in patients with advanced melanoma. The purpose of this study is to investigate the safety and efficacy of concurrent WBRT and ipilimumab. A retrospective analysis was conducted of 13 consecutive patients treated with WBRT within 30 days of ipilimumab administration. Radiographic response, as measured by serial magnetic resonance imaging scans post-treatment, was graded by modified World Health Organization (mWHO) and immune-related response criteria (irRC) in the 9 patients with follow-up imaging. Treatment-related toxicity was prospectively assessed during treatment. Four of nine patients (44 %) experienced partial response or stable central nervous system (CNS) disease as measured by mWHO criteria. This number increased to 5 patients (56 %) when irRC criteria were used. Rates of treatment-related neurologic toxicity were low with only one patient experiencing grade 3-4 neurologic toxicity. There was a high rate of intratumoral hemorrhage in this patient population, with 10 of 10 patients with post-treatment imaging demonstrating new or increased intratumoral bleeding after WBRT. This retrospective study demonstrates that the primary pattern of CNS response to WBRT and ipilimumab is stable disease and not regression of BM. Furthermore, while the combination of WBRT and ipilimumab may offer promising efficacy, prospective studies are needed to further assess efficacy and toxicity.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
authors.forename: Naamit K
authors.initials: NK
authors.lastname: Gerber
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Young
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Barker
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Chan
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
authors.forename: Leigh
authors.initials: L
authors.lastname: Friguglietti
authors.forename: Kathryn
authors.initials: K
authors.lastname: Beal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D003131:Combined Modality Therapy / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000074324:Ipilimumab; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab