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Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases

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Abstract

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.

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Funding

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

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA

    Tyler P. Robin, Chad G. Rusthoven, Kelly Stuhr, Laurie E. Gaspar, Sana D. Karam, David Raben, Brian D. Kavanagh, Sameer K. Nath & Arthur K. Liu

  2. Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, USA

    Robert E. Breeze, Amanda Brill & Robin Saiki

  3. Department of Pediatrics, Cancer Center Biostatistics Core, University of Colorado and Children’s Hospital Colorado, Aurora, CO, USA

    Derek E. Smith

  4. Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA

    Karl D. Lewis & Rene Gonzalez

  5. Department of Radiation Oncology, University of Colorado Cancer Center, 1665 Aurora Court, Suite 1032, MS F706, Aurora, CO, 80045, USA

    Tyler P. Robin

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  1. Tyler P. Robin
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Corresponding author

Correspondence to Tyler P. Robin.

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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.

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Robin, T.P., Breeze, R.E., Smith, D.E. et al. Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases. J Neurooncol 140, 55–62 (2018). https://doi.org/10.1007/s11060-018-2930-5

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  • DOI: https://doi.org/10.1007/s11060-018-2930-5

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