Tissue spacers in brachytherapy: A systematic review and meta-analysis

To systematically evaluate the impact of tissue spacers on radiation dose reduction to organs at risk (OARs), treatment-related toxicity, and overall clinical outcomes in brachytherapy, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A thorough search of PubMed, Scopus, IEEE Xplore, Embase, and Web of Science was conducted (1990-2024). Eligible studies included randomized trials, prospective or retrospective cohorts, and dosimetric analyses examining spacer use in brachytherapy. Data were extracted on patient demographics, spacer characteristics, dosimetric outcomes, and toxicity. Meta-analyses were performed where at least three studies reported comparable quantitative data, using random-effects models to pool effect sizes. Forty-five studies met inclusion criteria; 24 contributed to quantitative pooling. In prostate brachytherapy, hydrogel or balloon spacers consistently lowered rectal dose metrics by approximately 15-50 % and significantly reduced Grade ≥ 2 gastrointestinal toxicity (risk ratio ∼0.42). For head and neck brachytherapy, custom acrylic or silicone spacers decreased jaw dose and markedly lowered osteoradionecrosis rates. In gynecologic cancers, spacer balloons or injectable gels yielded 10-20 % reductions in bladder or rectal doses. Across all sites, spacers generally did not compromise tumor coverage and were associated with fewer late complications and improved patient quality of life. Spacers substantially improve the therapeutic ratio in brachytherapy by reducing OAR doses and lowering clinically significant toxicities. While the evidence base supports integrating spacers into standard practice, further randomized, multicenter trials are warranted to refine optimal spacer designs, placement techniques, and cost-effectiveness analyses.