Radiation Therapy for Metastatic Bone Disease: Effectiveness and Harms

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.