title: Survival of patients with melanoma brain metastasis treated with stereotactic radiosurgery and active systemic drug therapies.
abstract: With new systemic therapies demonstrating activity in melanoma brain metastasis, most of the previously reported stereotactic radiosurgery (SRS) data are superseded. In this study, we report the outcomes (overall survival [OS] and brain control [BC]) and identify factors that associate with such outcomes in the era of modern systemic therapy.
  
  
  
  A total of 108 patients treated with SRS from 2010 to 2015 were included. Systemic treatment use within 6 weeks of SRS was noted. OS was defined as time from SRS to death or last follow-up, and BC was defined as absence of any active intracranial disease during follow-up. Univariate and multivariate Cox proportional hazard analyses were performed on clinico-pathological prognostic features associated with OS and BC.
  
  
  
  The median age was 64.3 years, and the median follow-up was 8.6 months. Seventy-nine (73.1%) patients received systemic treatment. The median OS were as follows: anti-CTLA4 - 7.5 months (95% CI: 4.4-15.6), anti-PD1 - 20.4 months (95% CI: 8.8 - N/A) and BRAF inhibitor (BRAFi) ± MEK inhibitor (MEKi) - 17.8 months (95% CI: 11.8 - N/A). Median BC was as follows: anti-CTLA4 - 7.5 months (95% CI: 4.0-15.6), anti-PD1 - 12.7 months (95% CI: 5.5 - N/A) and BRAFi ± MEKi - 12.7 months (95% CI: 8.3-18.5). In multivariate analysis, age and type of systemic therapy were strongly associated with OS. Age, Eastern Cooperative Oncology Group performance status, Graded Prognostic Assessment (GPA) score, and presence of symptoms were associated with BC.
  
  
  
  Favourable outcomes are seen in patients treated with SRS and with the best survival seen in patients treated with anti-PD1. Known independent prognostic factors for survival such as age and performance status and GPA score remain relevant in this setting.
authors.affiliation: Chris O Brien Lifehouse, Camperdown, NSW, Australia.
authors.forename: Ee Siang
authors.initials: ES
authors.lastname: Choong
authors.affiliation: Melanoma Institute Australia, The University of Sydney, NSW, Australia.
authors.forename: Serigne
authors.initials: S
authors.lastname: Lo
authors.affiliation: Melanoma Institute Australia, The University of Sydney, NSW, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Drummond
authors.affiliation: Melanoma Institute Australia, The University of Sydney, NSW, Australia; Genesis Cancer Care, Mater Radiation Oncology, North Sydney, Australia; Mater Hospital, North Sydney NSW, Australia.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Fogarty
authors.affiliation: Melanoma Institute Australia, The University of Sydney, NSW, Australia; Mater Hospital, North Sydney NSW, Australia; Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Menzies
authors.affiliation: Melanoma Institute Australia, The University of Sydney, NSW, Australia; Mater Hospital, North Sydney NSW, Australia; Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Guminski
authors.affiliation: Melanoma Institute Australia, The University of Sydney, NSW, Australia; Royal Prince Alfred Hospital, Camperdown, NSW Australia; Mater Hospital, North Sydney NSW, Australia.
authors.forename: Brindha
authors.initials: B
authors.lastname: Shivalingam
authors.affiliation: Genesis Cancer Care, Mater Radiation Oncology, North Sydney, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Clarke
authors.affiliation: Melanoma Institute Australia, The University of Sydney, NSW, Australia; Mater Hospital, North Sydney NSW, Australia; Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
authors.affiliation: Melanoma Institute Australia, The University of Sydney, NSW, Australia; Genesis Cancer Care, Mater Radiation Oncology, North Sydney, Australia; Mater Hospital, North Sydney NSW, Australia. Electronic address: angela.hong@sydney.edu.au.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods / Q000401:mortality; D049268:Positron-Emission Tomography; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D016634:Radiosurgery / Q000379:methods* / Q000401:mortality; D012878:Skin Neoplasms; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human
keywords: Anti-PD-1 antibody; BRAF inhibitors; Brain metastasis; Immunotherapy; Melanoma; Stereotactic radiosurgery; Targeted therapy