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Review article
peer-reviewed

Stereotactic Radiosurgery and Ipilimumab Versus Stereotactic Radiosurgery Alone in Melanoma Brain Metastases



Abstract

Benefits of stereotactic radiosurgery (SRS) have been well established in melanoma brain metastases (MBM). Immunotherapy agents such as ipilimumab (ipi) have recently demonstrated clinical efficacy in advanced disease as well. The theoretical synergistic effects of combining these therapies in MBM have not been explored in detail, however, we conducted a systematic review with meta-analysis of studies that compared combined SRS and ipi versus SRS alone in MBM. Medical Literature Analysis and Retrieval System Online (MEDLINE) and Central databases were used for our literature search, which was conducted by three reviewers. We included studies that examined SRS and ipilimumab compared to SRS alone in MBM. Pertinent results were tabulated in a standardized spreadsheet. Newcastle-Ottawa Scale (NOS) Risk of Bias Assessment and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method for rating evidence quality were used for qualitative analysis. Review Manager was used for statistical analysis. We identified four cohort studies that compared SRS plus ipi versus SRS alone in MBM. As per the GRADE criteria, we found low-quality evidence for survival benefits associated with combined treatment. Meta-analysis confirmed a significant benefit in survival for SRS and ipilimumab (hazard ratio 0.38, 95% confidence interval 0.28 – 0.52, p < 0.01). There were no significant differences between comparison groups for local control, distant brain control, radiation necrosis, or intracranial bleeding. We conclude that low-quality evidence exists for superior overall survival in MBM treated with SRS and ipilimumab compared to SRS without ipilimumab. There is also no increased risk of radiation necrosis and/or intracranial bleeding with combining radiation and immunotherapy in this setting.



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Review article
peer-reviewed

Stereotactic Radiosurgery and Ipilimumab Versus Stereotactic Radiosurgery Alone in Melanoma Brain Metastases


Author Information

Steven M. Nguyen Corresponding Author

Department of Civil Engineering, Carnegie Mellon University

Aurelio Castrellon

Breast Cancer Center, Memorial Cancer Institute

Oliver Vaidis

Department of Mathematics and Statistics, University of South Florida

Andrew E. Johnson

Department of Computer Science, University of Houston


Ethics Statement and Conflict of Interest Disclosures

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.


Review article
peer-reviewed

Stereotactic Radiosurgery and Ipilimumab Versus Stereotactic Radiosurgery Alone in Melanoma Brain Metastases


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Review article
peer-reviewed

Stereotactic Radiosurgery and Ipilimumab Versus Stereotactic Radiosurgery Alone in Melanoma Brain Metastases

Steven M. Nguyen">Steven M. Nguyen , Aurelio Castrellon">Aurelio Castrellon, Oliver Vaidis">Oliver Vaidis, Andrew E. Johnson">Andrew E. Johnson

  • Author Information
    Steven M. Nguyen Corresponding Author

    Department of Civil Engineering, Carnegie Mellon University

    Aurelio Castrellon

    Breast Cancer Center, Memorial Cancer Institute

    Oliver Vaidis

    Department of Mathematics and Statistics, University of South Florida

    Andrew E. Johnson

    Department of Computer Science, University of Houston


    Ethics Statement and Conflict of Interest Disclosures

    Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

    Acknowledgements


    Article Information

    Published: July 25, 2017

    DOI

    10.7759/cureus.1511

    Cite this article as:

    Nguyen S M, Castrellon A, Vaidis O, et al. (July 25, 2017) Stereotactic Radiosurgery and Ipilimumab Versus Stereotactic Radiosurgery Alone in Melanoma Brain Metastases. Cureus 9(7): e1511. doi:10.7759/cureus.1511

    Publication history

    Received by Cureus: April 24, 2017
    Peer review began: June 06, 2017
    Peer review concluded: July 13, 2017
    Published: July 25, 2017

    Copyright

    © Copyright 2017
    Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Benefits of stereotactic radiosurgery (SRS) have been well established in melanoma brain metastases (MBM). Immunotherapy agents such as ipilimumab (ipi) have recently demonstrated clinical efficacy in advanced disease as well. The theoretical synergistic effects of combining these therapies in MBM have not been explored in detail, however, we conducted a systematic review with meta-analysis of studies that compared combined SRS and ipi versus SRS alone in MBM. Medical Literature Analysis and Retrieval System Online (MEDLINE) and Central databases were used for our literature search, which was conducted by three reviewers. We included studies that examined SRS and ipilimumab compared to SRS alone in MBM. Pertinent results were tabulated in a standardized spreadsheet. Newcastle-Ottawa Scale (NOS) Risk of Bias Assessment and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method for rating evidence quality were used for qualitative analysis. Review Manager was used for statistical analysis. We identified four cohort studies that compared SRS plus ipi versus SRS alone in MBM. As per the GRADE criteria, we found low-quality evidence for survival benefits associated with combined treatment. Meta-analysis confirmed a significant benefit in survival for SRS and ipilimumab (hazard ratio 0.38, 95% confidence interval 0.28 – 0.52, p < 0.01). There were no significant differences between comparison groups for local control, distant brain control, radiation necrosis, or intracranial bleeding. We conclude that low-quality evidence exists for superior overall survival in MBM treated with SRS and ipilimumab compared to SRS without ipilimumab. There is also no increased risk of radiation necrosis and/or intracranial bleeding with combining radiation and immunotherapy in this setting.



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Steven M. Nguyen

Department of Civil Engineering, Carnegie Mellon University

For correspondence:
smnguyen@alumni.cmu.edu

Aurelio Castrellon

Breast Cancer Center, Memorial Cancer Institute

Oliver Vaidis

Department of Mathematics and Statistics, University of South Florida

Andrew E. Johnson

Department of Computer Science, University of Houston

Steven M. Nguyen

Department of Civil Engineering, Carnegie Mellon University

For correspondence:
smnguyen@alumni.cmu.edu

Aurelio Castrellon

Breast Cancer Center, Memorial Cancer Institute

Oliver Vaidis

Department of Mathematics and Statistics, University of South Florida

Andrew E. Johnson

Department of Computer Science, University of Houston