Single- Versus Multiple-Fraction Radiation Therapy for Painful Bone Metastases: A Systematic Review and Meta-analysis of Nonrandomized Studies

PURPOSE: Single-fraction radiation therapy (RT) is a convenient and cost-effective regimen for the palliation of painful bone metastases, but is still underused. Randomized controlled trials comparing single- versus multiple-fraction RT are limited by generalizability. We compared the pain response rates after single- versus multiple-fraction RT in nonrandomized studies. METHODS AND MATERIALS: We searched PubMed and Scopus from the inception of each database through August 2018. We sought to identify nonrandomized studies in which data on pain response rates could be extracted for single- and multiple-fraction RT. Our primary outcomes of interest were the overall and complete pain response rates in evaluable patients. The analysis was performed using a random-effects model with the Mantel-Haenszel method. RESULTS: Of the 3933 articles identified through our search, 9 met our inclusion criteria. Five of 9 included studies did not exclude patients with features of complicated bone metastases. A 1 × 8 Gy radiation schedule was frequently used in single-fraction therapy, and schedules of 5 × 4 Gy and 10 × 3 Gy were frequently used in multiple-fraction therapy. In the 9 studies, the overall response rate was 67% (884 of 1321 patients) for patients in the single-fraction arm and 70% (953 of 1360 patients) for those in the multiple-fraction arm (pooled odds ratio [OR]: 0.85; 95% confidence interval [CI], 0.66-1.08). In 5 studies, the complete response rate was 26% (195 of 753 patients) for patients in the single-fraction arm and 35% (289 of 821 patients) for those in the multiple-fraction arm (pooled OR: 0.89; 95% CI, 0.70-1.13). CONCLUSIONS: There were no significant differences in the overall and complete response rates between single- and multiple-fraction RT. The effectiveness of single-fraction regimens was shown in nonrandomized settings, which better reflect daily practice than randomized studies. The CIs for the pooled ORs included clinically meaningful differences, and the study results are inconclusive.