Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery.
Growing evidence suggests that immunotherapy and radiation therapy can be synergistic in the treatment of cancer. This study was performed to determine the effect of the relative timing and type of immune checkpoint therapy on the response of melanoma brain metastases (BrMets) to treatment with stereotactic radiosurgery (SRS).



Seventy-five melanoma patients with 566 BrMets were treated with both SRS and immune checkpoint therapy between 2007 and 2015 at a single institution. Immunotherapy and radiosurgery treatment of any single lesion were considered concurrent if SRS was administered within 4 weeks of immunotherapy. The impact of the timing and type of immunotherapy on the lesional response was determined with the Wilcoxon rank-sum test, which was used to compare the median percent lesion volume change 1.5, 3, and 6 months after SRS treatment, with significance determined by P = .0167 according to the Bonferroni correction for multiple comparisons.



Concurrent use of immunotherapy and SRS resulted in a significantly greater median percent reduction in the lesion volume at 1.5 (-63.1% vs -43.2%, P < .0001), 3 (-83.0% vs -52.8%, P < .0001), and 6 months (-94.9% vs -66.2%, P < .0001) in comparison with nonconcurrent therapy. The median percent reduction in the lesion volume was also significantly greater for anti-programmed cell death protein 1 (anti-PD-1) than anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) at 1.5 (-71.1% vs -48.2%, P < .0001), 3 (-89.3% vs -66.2%, P < .0001), and 6 months (-95.1% vs -75.9%, P = .0004).



The administration of immunotherapy within 4 weeks of SRS results in an improved lesional response of melanoma BrMets in comparison with treatment separated by longer than 4 weeks. Anti-PD-1 therapy also results in a greater lesional response than anti-CTLA-4 after SRS. Cancer 2016;122:3051-3058. © 2016 American Cancer Society.
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
Jack M
0000-0002-9522-6445
JM
Qian
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
James B
JB
Yu
Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
Harriet M
HM
Kluger
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut. veronica.chiang@yale.edu.|Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut. veronica.chiang@yale.edu.
Veronica L S
VL
Chiang
D001932:Brain Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000276:immunology*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology; D016634:Radiosurgery; D012189:Retrospective Studies; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D061665:Time-to-Treatment
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D061026:Programmed Cell Death 1 Receptor
anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4); anti-programmed cell death protein 1 (anti-PD-1); brain metastases; immunotherapy; melanoma; stereotactic radiosurgery