11549 Background: The treatment of high-risk soft tissue sarcoma of the trunk or the extremities consists of surgical resection with risk-adapted radiation therapy. Further treatment options which can significantly improve local and systemic tumor control including chemotherapy are not well established. Due to the heterogeneity of disease different systemic approaches as well as their application during different time points have been attempted. Methods: We conducted a literature search for randomized clinical trials in the treatment of localized, resectable high-risk soft tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints of overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model (ivhet) with the help of the Microsoft Excel add-in Meta-XL V5.3. Results: The literature search identified 25 studies including 3489 patients. The network analysis showed that adjuvant chemotherapy (adjCTx) results in a significant improvement in overall survival (HR = 0.86; CI-95%: 0.75-0.97; p = 0.017) compared to the standard treatment of surgery ± radiatherapy alone. Combined treatment with regional hyperthermia and neoadjuvant chemotherapy (HTx+nadjCTx) also improves OS (HR = 0.45; CI-95%: 0.20-1.00; p = 0.049). Preoperative chemotherapy alone (nadjCTx) as well as perioperative chemotherapy (periopCTx) resulted both in non-statistically significant improvements in OS (HR = 0.61; CI-95%: 0.29-1.29; p = 0.195) and (HR = 0.48; CI-95%: 0.15-1.55; p = 0.218). Histology-tailored neoadjuvant chemotherapy (tNaCTx) also showed no effect on overall survival (HR = 1.08; CI-95%: 0.45-2.61; p = 0.868). The analysis of DFS, LRFI and DRFI disclosed a similar pattern between the different treatment regimens. Conclusions: The addition of cytotoxic chemotherapy in resectable high-risk soft tissue sarcomas provides a measurable benefit in overall survival. Shifting of systemic therapy to the neoadjuvant setting and combination with regional hyperthermia might be favored. Predictive clinical and molecular markers are needed to evaluate and limit potentional risks prospectively going forward.
Pathological grade of tumorregression after neoadjuvant chemotherapy with doxorubicin/ifosfamid and regional hyperthermia correlates with survival outcomes in patients with high-risk soft tissue sarcoma
