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Structured Abstract
Objective:
This evidence report synthesizes the available evidence on radiation therapy for brain metastases.
Data sources:
We searched PubMed®, Embase®, Web of Science, Scopus, CINAHL®, clinicaltrials.gov, and published guidelines in July 2020; assessed independently submitted data; consulted with experts; and contacted authors.
Review methods:
The protocol was informed by Key Informants. The systematic review was supported by a Technical Expert Panel and is registered in PROSPERO (CRD42020168260). Two reviewers independently screened citations; data were abstracted by one reviewer and checked by an experienced reviewer. We included randomized controlled trials (RCTs) and large observational studies (for safety assessments), evaluating whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) alone or in combination, as initial or postoperative treatment, with or without systemic therapy for adults with brain metastases due to non-small cell lung cancer, breast cancer, or melanoma.
Results:
In total, 97 studies, reported in 190 publications, were identified, but the number of analyses was limited due to different intervention and comparator combinations as well as insufficient reporting of outcome data. Risk of bias varied; 25 trials were terminated early, predominantly due to poor accrual. Most studies evaluated WBRT, alone or in combination with SRS, as initial treatment; 10 RCTs reported on post-surgical interventions.
The combination treatment SRS plus WBRT compared to SRS alone or WBRT alone showed no statistically significant difference in overall survival (hazard ratio [HR], 1.09; confidence interval [CI], 0.69 to 1.73; 4 RCTs; low strength of evidence [SoE]) or death due to brain metastases (relative risk [RR], 0.93; CI, 0.48 to 1.81; 3 RCTs; low SoE). Radiation therapy after surgery did not improve overall survival compared with surgery alone (HR, 0.98; CI, 0.76 to 1.26; 5 RCTs; moderate SoE). Data for quality of life, functional status, and cognitive effects were insufficient to determine effects of WBRT, SRS, or post-surgical interventions.
We did not find systematic differences across interventions in serious adverse events radiation necrosis, fatigue, or seizures (all low or moderate SoE). WBRT plus systemic therapy (RR, 1.44; CI, 1.03 to 2.00; 14 studies; moderate SoE) was associated with increased risks for vomiting compared to WBRT alone.
Conclusion:
Despite the substantial research literature on radiation therapy, comparative effectiveness information is limited. There is a need for more data on patient-relevant outcomes such as quality of life, functional status, and cognitive effects.
Contents
- Preface
- Acknowledgments
- Key Informants
- Technical Expert Panel
- Peer Reviewers
- Evidence Summary
- Introduction
- Methods
- Results
- Description of Included Evidence
- Key Question 1. What is the effectiveness of WBRT, alone or in combination with SRS or systemic therapies, as initial treatment in patients with brain metastases on patient-relevant outcomes, such as overall survival and quality of life?
- Key Question 2. What is the effectiveness of SRS/fractionated stereotactic radiation as initial treatment in patients with brain metastases on patient-relevant outcomes, such as overall survival and quality of life?
- Key Question 3. What is the effectiveness (or comparative effectiveness) of postoperative SRS compared to WBRT, observation, or preoperative SRS in patients with brain metastases on patient-relevant outcomes, such as overall survival and quality of life?
- Key Question 4. What are the adverse effects (i.e., serious harms) of WBRT, SRS, and systemic therapies for patients with brain metastases (either alone or in combination)?
- Discussion
- References
- Abbreviations and Acronyms
- Appendixes
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.
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).
- NLM CatalogRelated NLM Catalog Entries
- Radiation Therapy for Brain Metastases: A Systematic Review.[Pract Radiat Oncol. 2021]Radiation Therapy for Brain Metastases: A Systematic Review.Garsa A, Jang JK, Baxi S, Chen C, Akinniranye O, Hall O, Larkin J, Motala A, Hempel S. Pract Radiat Oncol. 2021 Sep-Oct; 11(5):354-365. Epub 2021 Jun 9.
- Management of single brain metastasis: a practice guideline.[Curr Oncol. 2007]Management of single brain metastasis: a practice guideline.Mintz A, Perry J, Spithoff K, Chambers A, Laperriere N. Curr Oncol. 2007 Aug; 14(4):131-43.
- Review Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.[Cochrane Database Syst Rev. 2017]Review Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.Patil CG, Pricola K, Sarmiento JM, Garg SK, Bryant A, Black KL. Cochrane Database Syst Rev. 2017 Sep 25; 9(9):CD006121. Epub 2017 Sep 25.
- Medical and health economic assessment of radiosurgery for the treatment of brain metastasis.[GMS Health Technol Assess. 2009]Medical and health economic assessment of radiosurgery for the treatment of brain metastasis.Müller-Riemenschneider F, Schwarzbach C, Bockelbrink A, Ernst I, Vauth C, Willich SN, von der Schulenburg JM. GMS Health Technol Assess. 2009 Mar 9; 5:Doc03. Epub 2009 Mar 9.
- Review Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.[Cochrane Database Syst Rev. 2010]Review Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.Patil CG, Pricola K, Garg SK, Bryant A, Black KL. Cochrane Database Syst Rev. 2010 Jun 16; (6):CD006121. Epub 2010 Jun 16.
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