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While the European Society for Medical Oncology guidelines take notice of a shift towards a neoadjuvant (neoadj.) RT approach, the American Society for Radiation Oncology’s guidelines clearly favour a neoadj. approach citing debilitating long-term adverse effects when RT is applied postoperatively. This study aims to examine these irradiation-associated adverse events for adjuvant (adj.) RT while also focusing on prognostic factors for disease outcome including local control.

In the course of this retrospective study, data of 106 patients with extremity soft-tissue sarcomas diagnosed between 1997 and 2021, of which 40 received adj. RT, was acquired from a high-volume sarcoma treatment centre’s clinical and radiological information systems. This data was then analysed for radiation-associated side effects, as well as predictive factors of overall survival (OS), disease-free survival (DSF), local control (LC) and surgery complications.

For the 106 patients included, the median follow-up period was 26 months and the 1-, 2- and 5-year OS reached were 89%, 76.4% and 58.3%, respectively. 3.8% underwent neoadjuvant (neoadj.) RT and 37.7% received adjuvant (adj.) RT: the majority intensity-modulated radiation therapy (IMRT). Negative prognostic factors for OS were lymph node involvement, metastatic disease and tumour of ≥8cm, while surgery and a higher adj. total irradiation dose if having received adj. RT was found to be beneficial.
87.5% experienced side effects from RT, mainly radiation dermatitis for 67.5%, but only 40.0% had any adverse event ≥2nd grade according to CTCAE. Long-time function-limiting side effects like joint stiffness, oedema and tissue fibrosis occurred in 45.0% of patients; 10% for ≥2nd grade function-limiting adverse events. More time between surgery and adj. RT was found to be beneficial for the patients while joint infiltrating sarcomas were more likely to come with more severe long-time function-limiting events.
29.3% experienced surgery complications or a vacuum-assisted closure, most requiring a secondary invasive procedure. 7.5% experienced trouble with their wounds after having gone through adj. RT.

This study found a low rate of long-time function-limiting side effects with adj. RT even with high irradiation doses while at the same time attesting to the fact that RT is highly beneficial to local control. Recurrences can be avoided with high-dose radiation, especially for high-grade G2- and G3-sarcomas even after complete R0-resection. Hence, adj. RT should be seriously considered when planning patients’ treatment, especially when treating patients presenting with high-grade sarcomas. For the majority of patients, RT involved IMRT which supports the idea that this has come to be the RT technique of choice. With the high benefit of specialised surgery, an interdisciplinary approach including complete resection and adj. RT should be further pursued and adverse events and patients’ quality of life further investigated.