Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases

J Neurooncol. 2018 Oct;140(1):55-62. doi: 10.1007/s11060-018-2930-5. Epub 2018 Jun 16.


Introduction: Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery.

Methods: We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery.

Results: Thirty-eight patients were included with a median follow-up of 31.6 months. Two-year local control was 92%. Median time to out-of-field CNS and extra-CNS progression were 8.4 and 7.9 months, respectively. Median progression-free survival (PFS) was 3.4 months and median overall survival (OS) was not reached (NR). Twenty-five patients (66%) received anti-CTLA4 and 13 patients (34%) received anti-PD-1+/-anti-CTLA4. Compared with anti-CTLA4, patients that received anti-PD-1+/-anti-CTLA4 had significant improvements in time to out-of-field CNS progression (p = 0.049), extra-CNS progression (p = 0.015), and PFS (p = 0.043), with median time to out-of-field CNS progression of NR vs. 3.1 months, median time to extra-CNS progression of NR vs. 4.4 months, and median PFS of 20.3 vs. 2.4 months. Six patients (16%) developed grade ≥ 2 CNS toxicities (grade 2: 3, grade 3: 3, grade 4/5: 0).

Conclusions: Excellent outcomes were observed in patients that initiated CPIs within 8 weeks of undergoing radiosurgery for newly diagnosed MBM. There appears to be an advantage to anti-PD-1 or combination therapy compared to anti-CTLA4.

Keywords: Anti-CTLA4; Anti-PD-1; Brain metastases; Immune checkpoint inhibitors; Melanoma; Radiosurgery.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies / therapeutic use*
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / secondary
  • Brain Neoplasms* / surgery
  • CTLA-4 Antigen / immunology*
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Melanoma / pathology*
  • Programmed Cell Death 1 Receptor / immunology*
  • Progression-Free Survival
  • Radiosurgery / methods*
  • Retrospective Studies
  • Statistics, Nonparametric
  • Treatment Outcome


  • Antibodies
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor