JUNE 2021 SYSTEMATIC REVIEW Radiation Therapy for Brain Metastases In Partnership with Comparative Effectiveness Review Number 242 Radiation Therapy for Brain Metastases Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov and Patient-Centered Outcomes Research Institute 1828 L Street, NW, Ste. 900 Washington, DC 20036 www.pcori.org Contract No. 290-2015-00010-I Prepared by: Southern California Evidence-based Practice Center Santa Monica, CA Investigators: Adam Garsa, M.D. Julie K. Jang, M.D., Ph.D. Sangita Baxi, M.A.S, M.Phil. Christine Chen, M.D. Olamigoke Akinniranye, M.S. Owen Hall, M.S. Jody Larkin, M.S. Aneesa Motala, B.A. Sydne Newberry, Ph.D. Susanne Hempel, Ph.D. AHRQ Publication No. 21-EHC021 PCORI® Publication No. 2020-SR-02 June 2021 This report is based on research conducted by the Southern California Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00010-I). The Patient-Centered Outcomes Research Institute® (PCORI®) funded the report (No. 2020-SR-02). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ or PCORI. Therefore, no statement in this report should be construed as an official position of PCORI, AHRQ, or the U.S. Department of Health and Human Services. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. The information in this report is intended to help healthcare decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients. This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders. PCORI®, AHRQ, or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied. AHRQ appreciates appropriate acknowledgment and citation of its work. Suggested language for acknowledgment: This work was based on an evidence report, Radiation Therapy for Brain Metastases, by the Evidence-based Practice Center Program at the Agency for Healthcare Research and Quality (AHRQ). Suggested citation: Garsa A, Jang JK, Baxi S, Chen C, Akinniranye O, Hall O, Larkin J, Motala A, Newberry S, Hempel S. Radiation Therapy for Brain Metastases. Comparative Effectiveness Review No. 242. (Prepared by the Southern California Evidence-based Practice Center under Contract No. 290-2015-00001-I.) AHRQ Publication No. 21-EHC021. PCORI Publication No. 2020-SR-02. Rockville, MD: Agency for Healthcare Research and Quality; June 2021. DOI: https://doi.org/10.23970/AHRQEPCCER242, Posted final reports are located on the Effective Health Care Program search page. ii Preface The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and private-sector organizations in their efforts to improve the quality of healthcare in the United States. These reviews provide comprehensive, science-based information on common, costly medical conditions, and new healthcare technologies and strategies. The Patient-Centered Outcomes Research Institute® (PCORI®) was established to fund research that helps patients and caregivers make better informed healthcare choices. To fulfill its authorizing mandate, PCORI partners with AHRQ to generate evidence synthesis products and make comparative effectiveness research more available to patients and providers. Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for practice, systematic reviews can help clarify whether assertions about the value of the intervention are based on strong evidence from clinical studies. For more information about AHRQ EPC systematic reviews, see www.effectivehealthcare.ahrq.gov/about/epc/evidence-synthesis. AHRQ expects that these systematic reviews will be helpful to health plans, providers, purchasers, government programs, and the healthcare system as a whole. Transparency and stakeholder input are essential to the Effective Health Care Program. Please visit the website (www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an email list to learn about new program products and opportunities for input. If you have comments on this systematic review, they may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 5600 Fishers Lane, Rockville, MD 20857, or by email to [email protected]. David Meyers, M.D. Arlene S. Bierman, M.D., M.S. Acting Director Director, Center for Evidence and Practice Agency for Healthcare Research and Quality Improvement Agency for Healthcare Research and Quality Nakela Cook, M.D., M.P.H. William Lawrence, M.D., M.S. Executive Director Senior Clinical Advisor Patient-Centered Outcomes Research Institute Office of the Chief Engagement and Dissemination Officer Patient-Centered Outcomes Research Institute Christine Chang, M.D., M.P.H. Lionel Bañez, M.D. Acting Director Task Order Officer Evidence-based Practice Center Program Center for Evidence and Practice Center for Evidence and Practice Improvement Improvement Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Michelle Althuis, Ph.D., M.A. Jennie Dalton Bowen, M.P.H. Associate Director Program Officer Patient-Centered Outcomes Research Institute Patient-Centered Outcomes Research Institute iii Acknowledgments The authors gratefully acknowledge the following individuals for their contributions to this project: Lionel Bañez, Jennie Dalton Bowen, Lisa Bradfield, and Ethan Balk for helpful comments. We also thank the authors Paul Brown, Lois Browne, Peter Graham, Siow Ming Lee, Mark Middleton, Alan Nichol, Stephanie Pugh, Srinivas Raman, and Daniel Roos for additional data or clarifications regarding data. In addition, we would like to thank Armenda Bialas and Lea Xenakis for project assistance. Key Informants In designing the study questions, the EPC consulted several Key Informants who represent the end-users of research. The EPC sought the Key Informant input on the priority areas for research and synthesis. Key Informants are not involved in the analysis of the evidence or the writing of the report. Therefore, in the end, study questions, design, methodological approaches, and/or conclusions do not necessarily represent the views of individual Key Informants. Key Informants must disclose any financial conflicts of interest greater than $5,000 and any other relevant business or professional conflicts of interest. Because of their role as end-users, individuals with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any conflicts of interest. The list of Key Informants who provided input to this report follows: Ralph DeVitto Sharon Mesmer American Brain Tumor Association Patient Advocate Chicago, IL Los Angeles, CA Rebecca Kirch, J.D. Hans Messersmith, M.P.H. National Patient Advocate Foundation American Society of Clinical Oncology Washington, DC (ASCO) Alexandria, VA Tim Kruser, M.D. Northwestern Memorial Hospital Debbie Robins, M.S., CFRE Northwestern University Feinberg School of American Brain Tumor Association Medicine Chicago, IL American Society for Radiation Oncology (ASTRO) Nicole Willmarth, Ph.D. Chicago, IL American Brain Tumor Association Chicago, IL iv Technical Expert Panel In designing the study questions and methodology at the outset of this report, the EPC consulted several technical and content experts. Broad expertise and perspectives were sought. Divergent and conflicted opinions are common and perceived as healthy scientific discourse that results in a thoughtful, relevant systematic review. Therefore, in the end, study questions, design, methodologic approaches, and/or conclusions do not necessarily represent the views of individual technical and content experts. Technical Experts must disclose any financial conflicts of interest greater than $5,000 and any other relevant business or professional conflicts of interest. Because of their unique clinical or content expertise, individuals with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any potential