Balancing the dose: A meta-analysis of preoperative radiotherapy strategies for soft tissue sarcomas

Purpose: Soft tissue sarcomas (STS) are a rare and diverse group of tumors. Management of STS typically involves a multidisciplinary approach, including surgery, radiotherapy (RT), and chemotherapy, with surgery remaining the cornerstone of treatment. Radiotherapy, both preoperative and postoperative, has been shown to improve local control. Hypofractionation has shown promising results in other malignancies and may offer similar benefits in STS. This study systematically reviews the efficacy and safety of different preoperative RT fractionation schedules, focusing on major wound complications (MWC) and late toxicity. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Cochrane Library, and Embase were searched for studies on preoperative RT in STS. Included studies were categorized into conventional RT, moderate hypofractionation, and ultra-hypofractionation. Meta-analysis was performed on MWC and late toxicity (≥ grade 3) using a random-effects model. Statistical heterogeneity was assessed using I-squared and Tau statistics. Results: Thirty studies with 2288 patients were included. The pooled overall rate of MWC was 18 % (95 % CI: 10–27 %) for conventional RT, and 29 % (95 % CI: 24–34 %) for moderate hypofractionation. The pooled overall rate of late toxicity was 5 % (95 % CI: 0–12 %) and 4 % (95 % CI: 2–6 %), respectively. Based on descriptive data, the MWC rates of the ultra-hypofractionated group did not exceed 41 %, with one study reporting a rate of 41 % and the remaining studies reporting rates no higher than 32 %. For toxicity, a wide range of toxicity rates (1–16 %) was reported. Conclusion: Moderate hypofractionation appears to maintain oncological outcomes while balancing toxicity and wound complications. Reported MWC rates of ultra-hypofractionation regimens, based on descriptive data from heterogeneous individual studies remained below 41 %. However, these outcomes are not derived from pooled analysis. This approach should not yet be used in clinical practice, and randomized controlled trials are needed to establish its efficacy and safety in STS patients.