Single- Versus Multiple-Fraction Radiation Therapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis of Non-Randomized Studies

Abstract Purpose Single-fraction radiation therapy (RT) is a convenient and cost-effective regimen for the palliation of painful bone metastases, but is still underutilized. 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 non-randomized studies. Methods and Materials We searched PubMed and Scopus from the inception of each database through August 2018. We sought to identify non-randomized studies in which data on the 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. Analysis was performed using a random-effects model with the Mantel-Haenszel method. Results Of the 3933 articles identified through our search, nine met our inclusion criteria. Five of the nine included studies did not exclude patients with features of complicated bone metastases. A 1 x 8 Gy radiation schedule was frequently used in single-fraction therapy; schedules of 5 x 4 Gy and 10 x 3 Gy were frequently used in multiple-fraction therapy. In the nine studies, the overall response rate was 67% (884/1321) for patients in the single-fraction arm and 70% (953/1360) for those in the multiple-fraction arm (pooled odds ratio, 0.85; 95% confidence interval, 0.66–1.08). In five studies, the complete response rate was 26% (195/753) for patients in the single-fraction arm and 35% (289/821) for those in the multiple-fraction arm (pooled odds ratio, 0.89; 95% confidence interval, 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 non-randomized settings, which better reflect daily practice than randomized studies. The confidence intervals for the pooled odds ratios included clinically meaningful differences, and the study results are inconclusive.