Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents

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...

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Main Authors:	Sahaja Acharya, MD, Mustafaa Mahmood, BS, Daniel Mullen, DDS, MS, Deshan Yang, PhD, Christina I. Tsien, MD, Jiayi Huang, MD, Stephanie M. Perkins, MD, Keith Rich, MD, Michael Chicoine, MD, Eric Leuthardt, MD, Joshua Dowling, MD, Gavin Dunn, MD, PhD, Jesse Keller, MD, Clifford G. Robinson, MD, Christopher Abraham, MD
Format:	Article
Language:	English
Published:	Elsevier 2017-10-01
Series:	Advances in Radiation Oncology
Online Access:	http://www.sciencedirect.com/science/article/pii/S2452109417301082

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record_format	Article
spelling	doaj-263aea1684d249dc8f440ca130c8b6ea2020-11-24T23:14:28ZengElsevierAdvances in Radiation Oncology2452-10942017-10-0124572580Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agentsSahaja Acharya, MD0Mustafaa Mahmood, BS1Daniel Mullen, DDS, MS2Deshan Yang, PhD3Christina I. Tsien, MD4Jiayi Huang, MD5Stephanie M. Perkins, MD6Keith Rich, MD7Michael Chicoine, MD8Eric Leuthardt, MD9Joshua Dowling, MD10Gavin Dunn, MD, PhD11Jesse Keller, MD12Clifford G. Robinson, MD13Christopher Abraham, MD14Department of Radiation Oncology, Washington University, St. Louis, MissouriDepartment of Radiation Oncology, Washington University, St. Louis, MissouriDepartment of Radiation Oncology, Washington University, St. Louis, MissouriDepartment of Radiation Oncology, Washington University, St. Louis, MissouriDepartment of Radiation Oncology, Washington University, St. Louis, MissouriDepartment of Radiation Oncology, Washington University, St. Louis, MissouriDepartment of Radiation Oncology, Washington University, St. Louis, MissouriDepartment of Neurosurgery, Washington University, St. Louis, MissouriDepartment of Neurosurgery, Washington University, St. Louis, MissouriDepartment of Neurosurgery, Washington University, St. Louis, MissouriDepartment of Neurosurgery, Washington University, St. Louis, MissouriDepartment of Neurosurgery, Washington University, St. Louis, MissouriDepartment of Medical Oncology, Washington University, St. Louis, MissouriDepartment of Radiation Oncology, Washington University, St. Louis, MissouriDepartment of Radiation Oncology, Washington University, St. Louis, Missouri; Corresponding author. Department of Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, St. Louis, MO 63110.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.http://www.sciencedirect.com/science/article/pii/S2452109417301082
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Sahaja Acharya, MD Mustafaa Mahmood, BS Daniel Mullen, DDS, MS Deshan Yang, PhD Christina I. Tsien, MD Jiayi Huang, MD Stephanie M. Perkins, MD Keith Rich, MD Michael Chicoine, MD Eric Leuthardt, MD Joshua Dowling, MD Gavin Dunn, MD, PhD Jesse Keller, MD Clifford G. Robinson, MD Christopher Abraham, MD
spellingShingle	Sahaja Acharya, MD Mustafaa Mahmood, BS Daniel Mullen, DDS, MS Deshan Yang, PhD Christina I. Tsien, MD Jiayi Huang, MD Stephanie M. Perkins, MD Keith Rich, MD Michael Chicoine, MD Eric Leuthardt, MD Joshua Dowling, MD Gavin Dunn, MD, PhD Jesse Keller, MD Clifford G. Robinson, MD Christopher Abraham, MD Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents Advances in Radiation Oncology
author_facet	Sahaja Acharya, MD Mustafaa Mahmood, BS Daniel Mullen, DDS, MS Deshan Yang, PhD Christina I. Tsien, MD Jiayi Huang, MD Stephanie M. Perkins, MD Keith Rich, MD Michael Chicoine, MD Eric Leuthardt, MD Joshua Dowling, MD Gavin Dunn, MD, PhD Jesse Keller, MD Clifford G. Robinson, MD Christopher Abraham, MD
author_sort	Sahaja Acharya, MD
title	Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents
title_short	Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents
title_full	Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents
title_fullStr	Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents
title_full_unstemmed	Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents
title_sort	distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents
publisher	Elsevier
series	Advances in Radiation Oncology
issn	2452-1094
publishDate	2017-10-01
description	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.
url	http://www.sciencedirect.com/science/article/pii/S2452109417301082
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Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents

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