Stereotactic Body Radiation Therapy vs. Conventional External Beam Radiation Therapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis of Randomized Trials

Abstract

<h3>Purpose/Objective(s)</h3> The magnitude of benefit and toxicity of stereotactic body radiation therapy (SBRT) compared with conventional external beam radiation therapy (cEBRT) in treating symptomatic bone metastases is unclear due to the conflicting results from randomized controlled trials (RCTs). We performed a systematic review and meta-analysis to compare the efficacy and safety of SBRT and cEBRT in patients with previously unirradiated painful bone metastases. <h3>Materials/Methods</h3> We searched various databases and major oncologic conference proceedings from inception to Oct 2021 for RCTs comparing SBRT with cEBRT for previously unirradiated painful bone metastases. The outcomes of interest were efficacy (overall and complete pain response rates, local progression, overall survival (OS) and quality of life (QoL)) and safety (post-irradiation fractures, pain flares and radiation myelopathy). We assessed the methodologic quality of individual trials using the revised Cochrane risk-of-bias (RoB2) tool. We performed one-stage individual patient data meta-analysis using multilevel logistic regression model. Sensitivity analyses were conducted using two-stage frequentist and Bayesian meta-analyses. We adopted Synthesis Without Meta-analysis (SWiM) approach to summarize adverse events and quality of life outcomes. We assessed the certainty of the evidence for the efficacy outcomes using GRADE approach. <h3>Results</h3> Six RCTs including 894 patients were identified. Five of the included trials had low risk of bias. There was no significant difference in overall pain response rates at 3 months between SBRT and cEBRT (odd ratio (OR), 1.10; 95% confidence interval (CI), 0.84-1.44; P, 0.48; GRADE, moderate certainty). SBRT significantly improved complete pain response rates at 3 months (OR, 3.38; 95% CI, 1.88-6.07; P< 0.01; GRADE, high certainty) and reduced local progression rates (OR, 0.15; 95% CI, 0.04-0.53; P< 0.01; GRADE, high certainty), compared to cEBRT. Sensitivity analyses showed consistent findings. SBRT was associated with a modest increase in pain flare rates, compared to cEBRT. There were no significant differences between the two groups in OS, post-irradiation fracture and radiation myelopathy. The QoL was similar, except for improved perception of financial burden with SBRT at 4 weeks. <h3>Conclusion</h3> Among the patients with previously unirradiated symptomatic bone metastases, SBRT significantly improved complete but not overall pain response rates at 3 months and delayed local progression without adversely impacting on the quality of life and overall survival, compared to cEBRT. SBRT was associated with a modest increase in the pain flare rates, compared to cEBRT.