title: Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy.
abstract: BACKGROUND
  The anti-programmed death-1 (anti-PD-1) therapy nivolumab has significant clinical activity in patients with metastatic melanoma. However, little is known about the safety and outcomes in patients receiving anti-PD-1 therapy and stereotactic radiation for the treatment of brain metastases (BMs).
  
  
  METHODS
  Data were analyzed retrospectively from two prospective nivolumab protocols enrolling 160 patients with advanced resected and unresectable melanoma at a single institution. Patients were included if BMs were diagnosed and treated with stereotactic radiation within 6 months of receiving nivolumab. The primary end point of this study was neurotoxicity; secondary end points included BM control and survival.
  
  
  RESULTS
  Twenty-six patients with a total of 73 BMs treated over 30 sessions were identified. Radiation was administered before, during and after nivolumab in 33 lesions (45%), 5 lesions (7%), and 35 lesions (48%), respectively. All BMs were treated with stereotactic radiosurgery (SRS) in a single session except 12 BMs treated with fractionated stereotactic radiation therapy, nine of which were in the postoperative setting. One patient experienced grade 2 headaches following SRS with symptomatic relief with steroid treatment. No other treatment-related neurologic toxicities or scalp reactions were reported. Eight (11%) local BM failures with a ≥20% increase in volume were noted. Of these lesions, hemorrhage was noted in 4, and edema was noted in 7. Kaplan-Meier estimates for local BM control following radiation at 6 and 12 months were 91% and 85%, respectively. Median overall survival (OS) from the date of stereotactic radiation and nivolumab initiation was 11.8 and 12.0 months, respectively, in patients receiving nivolumab for unresected disease (median OS was not reached in patients treated in the resected setting).
  
  
  CONCLUSIONS
  In our series, stereotactic radiation to melanoma BMs is well tolerated in patients who received nivolumab. BM control and OS appear prolonged compared with standard current treatment. Prospective evaluation is warranted.
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
authors.forename: K A
authors.initials: KA
authors.lastname: Ahmed
authors.affiliation: Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
authors.forename: D G
authors.initials: DG
authors.lastname: Stallworth
authors.affiliation: Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
authors.forename: P A S
authors.initials: PA
authors.lastname: Johnstone
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
authors.forename: L B
authors.initials: LB
authors.lastname: Harrison
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
authors.forename: J J
authors.initials: JJ
authors.lastname: Caudell
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
authors.forename: H H M
authors.initials: HH
authors.lastname: Yu
authors.affiliation: Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
authors.forename: A B
authors.initials: AB
authors.lastname: Etame
authors.affiliation: NYU Langone Medical Center, New York.
authors.forename: J S
authors.initials: JS
authors.lastname: Weber
authors.affiliation: Department of Oncology, Georgetown-Lombardi Comprehensive Cancer Center, Washington Department of Medicine, Medstar-Georgetown University Hospital, Washington, USA geoffrey.t.gibney@gunet.georgetown.edu.
authors.forename: G T
authors.initials: GT
authors.lastname: Gibney
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D016634:Radiosurgery / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab
keywords: anti-PD-1 therapy; melanoma; nivolumab; stereotactic radiation