Journal of Neuro-Oncology

, Volume 140, Issue 1, pp 55–62 | Cite as

Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases

  • Tyler P. RobinEmail author
  • Robert E. Breeze
  • Derek E. Smith
  • Chad G. Rusthoven
  • Karl D. Lewis
  • Rene Gonzalez
  • Amanda Brill
  • Robin Saiki
  • Kelly Stuhr
  • Laurie E. Gaspar
  • Sana D. Karam
  • David Raben
  • Brian D. Kavanagh
  • Sameer K. Nath
  • Arthur K. Liu
Clinical Study



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.


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.


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).


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.


Melanoma Brain metastases Radiosurgery Immune checkpoint inhibitors Anti-PD-1 Anti-CTLA4 



This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with Ethical Standards

Conflict of interest

Karl Lewis: Consultant: Roche, Genentech. David Raben: Consultant: Astra Zeneca; Advisory Boards: Merck and EMD Serono and Genentech. All remaining authors have declared no conflicts of interest.

Supplementary material

11060_2018_2930_MOESM1_ESM.pdf (107 kb)
Supplementary material 1 (PDF 106 KB)
11060_2018_2930_MOESM2_ESM.pdf (104 kb)
Supplementary material 2 (PDF 103 KB)
11060_2018_2930_MOESM3_ESM.docx (16 kb)
Supplementary material 3 (DOCX 16 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tyler P. Robin
    • 1
    • 5
    Email author
  • Robert E. Breeze
    • 2
  • Derek E. Smith
    • 3
  • Chad G. Rusthoven
    • 1
  • Karl D. Lewis
    • 4
  • Rene Gonzalez
    • 4
  • Amanda Brill
    • 2
  • Robin Saiki
    • 2
  • Kelly Stuhr
    • 1
  • Laurie E. Gaspar
    • 1
  • Sana D. Karam
    • 1
  • David Raben
    • 1
  • Brian D. Kavanagh
    • 1
  • Sameer K. Nath
    • 1
  • Arthur K. Liu
    • 1
  1. 1.Department of Radiation OncologyUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Department of NeurosurgeryUniversity of Colorado School of MedicineAuroraUSA
  3. 3.Department of Pediatrics, Cancer Center Biostatistics CoreUniversity of Colorado and Children’s Hospital ColoradoAuroraUSA
  4. 4.Division of Medical Oncology, Department of MedicineUniversity of Colorado School of MedicineAuroraUSA
  5. 5.Department of Radiation OncologyUniversity of Colorado Cancer CenterAuroraUSA

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