Low rate of function-limiting side effects with high-dose adjuvant radiotherapy in high-grade soft tissue extremity sarcomas: a retrospective single-center analysis over 10 years

Abstract

Background: Over the years, radiotherapy has been established as a tool to improve local control for high-grade sarcomas. Although the European Society for Medical Oncology guidelines has taken notice of a shift toward a neoadjuvant radiotherapy approach, the American Society for Radiation Oncology guidelines clearly favor a neoadjuvant approach, citing debilitating long-term adverse effects when radiotherapy is applied postoperatively. In this study, we examined these irradiation-associated adverse events for adjuvant radiotherapy and focused on the prognostic factors for disease outcome, including local control. Methods: In this retrospective study, data for 106 patients with extremity soft-tissue sarcomas diagnosed between 1997 and 2021, of which 40 received adjuvant radiotherapy, were collected from the clinical and radiological information systems of a high-volume sarcoma treatment center. These data were then analyzed for radiation-associated side effects as well as predictive factors for overall survival, disease-free survival, local control, and surgical complications. Results: Radiotherapy was beneficial to patients improving local control, especially for high-grade sarcomas, even when those were resected with negative margins. Side effects due to radiotherapy occurred in 87.5% of the patients, and these effects primarily included radiation dermatitis in 67.5%; however, only 40.0% had any adverse event of ≥ grade 2 according to Common Terminology Criteria for Adverse Events. Long-term function-limiting side effects occurred in 45.0% of the patients; 10% exhibited ≥ grade 2 function-limiting adverse events. Greater time between surgery and adjuvant radiotherapy was beneficial for the patients, whereas joint infiltrating sarcomas were associated with more severe long term, function-limiting adverse events. 28.3% of the patients experienced a recurrence at any location (median time 18.35 months) and in 16% the recurrence was local (median time 16.11 months), resulting in 1, 3, and 5 year disease-free survival rates of 74.1, 58.9, and 38.5% and local control rates of 78.7, 61.6, and 42.8% were observed, respectively. Conclusion: Recurrences may be avoided with high-dose radiation, especially for high-grade G2 and G3 sarcomas, even after complete R0 resection. This resulted in a low rate of severe long-term function-limiting adverse events. Thus, adjuvant radiotherapy should be seriously considered when planning patient treatment, especially when treating patients that present with high-grade sarcomas.