TY - JOUR
T1 - Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents
AU - Acharya, Sahaja
AU - Mahmood, Mustafaa
AU - Mullen, Daniel
AU - Yang, Deshan
AU - Tsien, Christina I.
AU - Huang, Jiayi
AU - Perkins, Stephanie M.
AU - Rich, Keith
AU - Chicoine, Michael
AU - Leuthardt, Eric
AU - Dowling, Joshua
AU - Dunn, Gavin
AU - Keller, Jesse
AU - Robinson, Clifford G.
AU - Abraham, Christopher
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/10
Y1 - 2017/10
N2 - Purpose Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively (P <.001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS + IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; P =.003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P =.001).One-year local control for SRS, SRS + IMT, and SRS + targeted therapy was 66%, 85%, and 72%, respectively (P =.044). On multivariate analysis, after adjusting for dose, SRS + IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P =.04). Conclusions SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result.
AB - Purpose Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively (P <.001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS + IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; P =.003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P =.001).One-year local control for SRS, SRS + IMT, and SRS + targeted therapy was 66%, 85%, and 72%, respectively (P =.044). On multivariate analysis, after adjusting for dose, SRS + IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P =.04). Conclusions SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result.
UR - http://www.scopus.com/inward/record.url?scp=85030841657&partnerID=8YFLogxK
U2 - 10.1016/j.adro.2017.07.003
DO - 10.1016/j.adro.2017.07.003
M3 - Article
C2 - 29204524
AN - SCOPUS:85030841657
SN - 2452-1094
VL - 2
SP - 572
EP - 580
JO - Advances in Radiation Oncology
JF - Advances in Radiation Oncology
IS - 4
ER -