Meta-analysis of 5-day preoperative radiotherapy for soft tissue sarcoma (5D-PREORTS)

Background and purpose: Although the role of conventionally fractionated radiotherapy (RT) in combination with surgery in the limb-sparing treatment of soft tissue sarcoma (STS) patients is well established, the effectiveness and safety of 5-day preoperative radiotherapy (RT) remain controversial. We performed a meta-analysis to evaluate the treatment outcomes of 5-day preoperative RT using > 5 Gy per fraction with contemporary radiotherapy techniques.Materials and methods: Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through March 2022 were used to identify eligible studies. Following the PRISMA and MOOSE guidelines, a meta- regression analysis was performed to assess possible correlations between variables and outcomes. A p-value < 0.05 was considered significant.Results: Nine prospective studies with 786 patients (median follow-up 35 months, 20-60 months) treated with preoperative RT delivered a median total of 30 Gy (25-40 Gy) in 5 fractions. The local control (LC), R0 margins, overall survival (OS), and distant relapse (DR) rates were 92.3% (95% CI: 87---97%), 84.5% (95% CI: 78---90%), 78% (95% CI: 70---86%), and 36% (95% CI: 70---86%). The meta-regression analysis identified a significant relationship between biological equivalent dose (BED) and larger tumor size for LC and R0 margins (p < 0.05). The subgroup analysis reveals that patients receiving BED > 90 (equivalent to 30 Gy in 5 fractions) had a higher LC control rate than BED < 90 (p < 0.0001). The complete pathologic response and amputation rates were 19% (95% CI: 13-26%) and 8.3% (95% CI: 0.5-15%). Amputation rates were higher in studies using the lowest and highest doses and were related to salvage surgery after recurrence and complications, respectively. The rate of wound complication and fibrosis grade 2 or worse was 30% (95% CI 23-38%) and 6.4% (95% CI 1.9-11%).Conclusion: A 5-day course of preoperative RT results in high LC and favorable R0 margins, with acceptable complication rates in most studies. Better local control and R0 margins were associated with regimens using higher BED, i.e., doses equal to or higher than 30 Gy when using 5 fractions.