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Cureus. 2017 Dec 13;9(12):e1943. doi: 10.7759/cureus.1943.

Effect of Gamma Knife Radiosurgery and Programmed Cell Death 1 Receptor Antagonists on Metastatic Melanoma.

Cureus

Nathan Nordmann, Molly Hubbard, Tyler Nordmann, Paul W Sperduto, H Brent Clark, Matthew A Hunt

Affiliations

  1. Neurosurgery, University of Minnesota Medical School.
  2. Department of Neurosurgery, University of Minnesota.
  3. Electrical Engineering, University of Minnesota.
  4. Minneapolis Radiation Oncology & Gamma Knife Center, University of Minnesota.
  5. Pathology, University of Minnesota.

PMID: 29468099 PMCID: PMC5811164 DOI: 10.7759/cureus.1943

Abstract

Learning objectives To evaluate radiation-induced changes in patients with brain metastasis secondary to malignant melanoma who received treatment with Gamma Knife radiosurgery (GKRS) and programmed cell death 1 (PD-1) receptor antagonists. Introduction  Stereotactic radiosurgery and chemotherapeutics are used together for treatment of metastatic melanoma and have been linked to delayed radiation-induced vasculitic leukoencephalopathy (DRIVL). There have been reports of more intense interactions with new immunotherapeutics targeting PD-1 receptors, but their interactions have not been well described and may result in an accelerated response to GKRS. Here we present data on subjects treated with this combination from a single institution. Methods Records from patients who underwent treatment for metastatic melanoma to the brain with GKRS from 2011 to 2016 were reviewed. Demographics, date of brain metastasis diagnosis, cause of death when applicable, immunotherapeutics, and imaging findings were recorded. The timing of radiation therapy and medications were also documented.  Results A total of 79 subjects were treated with GKRS, and 66 underwent treatment with both GKRS and immunotherapy. Regarding the 30 patients treated with anti-PD-1 immunotherapy, 21 patients received pembrolizumab, seven patients received nivolumab, and two patients received pembrolizumab and nivolumab. Serial imaging was available for interpretation in 25 patients, with 13 subjects who received GKRS and anti-PD-1 immunotherapy less than six weeks of each other. While four subjects had indeterminate/mixed findings on subsequent magnetic resonance imaging (MRI), nine subjects were noted to have progression. Two of these patients showed progression but subsequent imaging revealed a decrease in progression or improvement on MRI to previously targeted lesions by GKRS. None of the 13 subjects had surgery following their combined therapies. Conclusions This data suggests that there is need for further investigation of the role for concurrent treatment with PD-1 inhibitors and GKRS to enhance the treatment of metastatic melanoma. We present data on 13 patients who appear to have some radiologic benefit to this treatment combination, two of whom had radiographic pseudoprogression.

Keywords: immunotherapy; melanoma; radiosurgery

Conflict of interest statement

The authors have declared that no competing interests exist.

References

  1. Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):369-75 - PubMed
  2. Cancer. 2011 Apr 15;117(8):1687-96 - PubMed
  3. Cancer Immunol Res. 2016 Mar;4(3):179-82 - PubMed
  4. Neuro Oncol. 2017 Mar 1;19(3):454-456 - PubMed
  5. Oncoimmunology. 2016 Aug 19;5(9):e1214788 - PubMed
  6. Ophthal Plast Reconstr Surg. 2017 Jul/Aug;33(4):e82-e85 - PubMed
  7. J Neurosurg. 1998 Jan;88(1):11-20 - PubMed
  8. Nat Rev Cancer. 2012 Mar 22;12(4):252-64 - PubMed
  9. Minim Invasive Neurosurg. 2005 Aug;48(4):228-34 - PubMed
  10. Ann Oncol. 2016 Mar;27(3):434-41 - PubMed
  11. Curr Oncol Rep. 2013 Oct;15(5):483-91 - PubMed
  12. J Neurooncol. 2015 Oct;125(1):149-56 - PubMed
  13. N Engl J Med. 2015 Jun 25;372(26):2521-32 - PubMed
  14. Eur J Cancer. 1978 Apr;14(4):327-30 - PubMed
  15. Front Immunol. 2017 May 05;8:517 - PubMed
  16. Ann Transl Med. 2016 Mar;4(6):118 - PubMed
  17. J Skin Cancer. 2011;2011:845863 - PubMed
  18. Neurosurg Rev. 2014 Apr;37(2):193-201; discussion 201 - PubMed
  19. Lancet Oncol. 2015 Jul;16(7):795-803 - PubMed
  20. Ann Surg Oncol. 1994 Jan;1(1):38-44 - PubMed
  21. Int J Radiat Oncol Biol Phys. 2001 Apr 1;49(5):1339-49 - PubMed
  22. Cancer Immunol Res. 2016 Jun;4(6):481-7 - PubMed
  23. Br J Cancer. 1997;76(2):256-9 - PubMed
  24. J Oncol Pract. 2016 Jun;12 (6):536-42 - PubMed
  25. AJNR Am J Neuroradiol. 2011 Nov-Dec;32(10):1885-92 - PubMed
  26. J Thorac Oncol. 2015 Oct;10(10):e100-1 - PubMed
  27. Ther Adv Med Oncol. 2015 Mar;7(2):97-106 - PubMed
  28. J Clin Oncol. 2016 May 1;34(13):1510-7 - PubMed

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