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Structured Abstract
Objectives:
To evaluate the comparative effectiveness and harms of external beam radiation therapy (EBRT) for palliative treatment of metastatic bone disease (MBD).
Data sources:
Four electronic databases from 1985 to January 30, 2023; a targeted search for re-irradiation through January 30, 2023; reference lists; and a Federal Register notice.
Review methods:
Using predefined criteria and dual review, we selected randomized controlled trials (RCTs) and nonrandomized studies of interventions (NRSIs) comparing dose-fractionation schemes and EBRT delivery techniques (for initial radiation and re-irradiation, i.e., retreatment for recurrent or persistent pain) and EBRT alone versus in combination with other palliative treatments. Study risk of bias was assessed using predefined criteria. Strength of evidence (SOE) was assessed for the primary outcomes of pain, function, spinal cord compression relief, quality of life, and harms.
Results:
We included 53 RCTs and 31 NRSIs; most were fair quality. In patients receiving initial radiation for MBD there was a small increase in the likelihood of overall pain response (improved pain measures with stable or decreased analgesic use) for multiple fraction (MF) EBRT versus single fraction (SF) EBRT up to 4 weeks post-radiation therapy (SOE: moderate) and for higher dose (6 or 8 Gy) SF EBRT versus lower dose (4 Gy) SF EBRT up to 52 weeks post-radiation therapy (SOE: low). SF and MF EBRT did not differ at later followup (SOE: moderate) nor did comparisons of MF EBRT dose/fractions (SOE: moderate ≤12 weeks; low >12 weeks). Re-irradiation was more common with SF versus MF EBRT. Stereotactic body radiation therapy (SBRT) (SF or MF) was associated with a slightly higher (up to 20 weeks, SOE: low) and moderately higher (30 weeks; SOE: moderate) likelihood of overall pain response versus MF EBRT. For re-irradiation, SF and MF SBRT had a similar likelihood of overall pain response, as did SF versus MF EBRT (SOE: low for all). Harms may be similar across dose/fraction schemes and techniques; serious harms were rare. Comparative effectiveness evidence for EBRT was sparse.
Conclusions:
In patients with uncomplicated MBD receiving initial palliative radiotherapy, the likelihood of overall pain response for SF and MF EBRT is probably similar, particularly after 4 weeks; re-irradiation was more common with SF-EBRT. SF and MF SBRT may provide slightly greater likelihood of overall pain response versus MF EBRT; evidence is limited. SF and MF EBRT may have similar likelihoods of overall pain response in patients receiving re-irradiation. High-quality evidence comparing SBRT with EBRT is needed in populations with complicated and uncomplicated MBD, as is research on effectiveness of EBRT versus other treatments.
Update:
An addendum is located at the end of the main report, before the appendixes.
Contents
- Preface
- Acknowledgments
- Technical Expert Panel
- Peer Reviewers
- Executive Summary
- 1. Introduction
- 2. Methods
- 3. Results
- 3.1. Key Question 1. Effectiveness and Harms of Dose-Fractionation Schemes and Techniques for Delivery: Initial Radiation
- 3.2. Key Question 2. Effectiveness and Harms of Dose-Fractionation Schemes and Techniques for Delivery: Re-Irradiation
- 3.3. Key Question 3a. Effectiveness and Harms of EBRT Versus Another Single Treatment Modality
- 3.4. Key Question 3b. Effectiveness and Harms of EBRT Combined With Another Treatment Modality Versus EBRT Alone
- 3.5. Key Question 3c. Effectiveness and Harms of EBRT Combined With Another Treatment Modality Versus the Same Treatment Modality Alone
- 3.6. Contextual Questions
- 4. Discussion
- 5. References
- 6. Abbreviations and Acronyms
- Addendum
- Appendixes
- Appendix A. Methods
- Appendix B. Results Overview
- Appendix C. Contextual Questions
- Appendix D. Included Studies List
- Appendix E. Evidence Tables
- Appendix F. Quality Assessments
- Appendix G. Strength of Evidence
- Appendix H. Excluded Studies List
- Appendix I. Forest Plots
- Appendix J. Definitions of Magnitudes of Effect
- Appendix K. Appendix References
- Addendum Appendix. Evidence Table
Suggested citation:
Skelly AC, Chang E, Bordley J, Brodt ED, Selph S, Fu R, Yu Y, Holmes R, Dana T, Stabler-Morris S, Riopelle D, Chou R. Radiation Therapy for Metastatic Bone Disease: Effectiveness and Harms. Comparative Effectiveness Review No. 265. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 75Q80120D00006.) AHRQ Publication No. 23-EHC026. Rockville, MD: Agency for Healthcare Research and Quality; August 2023. doi: https://doi.org/10.23970/AHRQEPCCER265. Posted final reports are located on the Effective Health Care Program search page.
This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 75Q80120D00006). 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. Therefore, no statement in this report should be construed as an official position of AHRQ or of 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. Dr. Eric Chang is a physician with specialty expertise in radiation oncology and related clinical research, and served as a clinical expert and co-investigator for 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. Most AHRQ documents are publicly available to use for noncommercial purposes (research, clinical or patient education, quality improvement projects) in the United States, and do not need specific permission to be reprinted and used unless they contain material that is copyrighted by others. Specific written permission is needed for commercial use (reprinting for sale, incorporation into software, incorporation into for-profit training courses) or for use outside of the U.S. If organizational policies require permission to adapt or use these materials, AHRQ will provide such permission in writing.
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 Metastatic Bone Disease: Effectiveness and Harms, by the Evidence-based Practice Center Program at the Agency for Healthcare Research and Quality (AHRQ).
A representative from AHRQ served as a Contracting Officer’s Representative and reviewed the contract deliverables for adherence to contract requirements and quality. AHRQ did not directly participate in the literature search, determination of study eligibility criteria, data analysis, interpretation of data, or preparation or drafting of this report.
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