Introduction: Management of marginally resectable or unresectable soft tissue sarcomas (STS) in patients who are not candidates for neoadjuvant chemotherapy due to chemoresistant pathology or contraindications remains a challenge. Therefore, in these indications, we aimed to investigate a feasibility of 10x 3.25 Gy radiotherapy combined with regional hyperthermia (HT) that could be followed by surgery or 4x4 Gy radiotherapy with HT. Materials and methods: We recruited patients with locally advanced marginally resectable or unresectable STS who (1) presented chemoresistant STS subtype, or (2) progressed after neoadjuvant chemotherapy, or (3) were unfit for chemotherapy. The primary endpoint was the feasibility of the proposed regimen. Results: Thirty patients were enrolled. All patients received the first part of the treatment, namely radiotherapy with HT. Among them, 14 received the second part of radiotherapy with HT whereas 13 patients underwent surgery. Three patients did not complete the treatment protocol. The feasibility criteria were fulfilled in 90% of patients. Two patients developed distant metastases. One patient died due to distant progression. One patient developed rapid local recurrence after surgery. Conclusions: Hypofractionated radiotherapy with HT is a feasible treatment for marginally resectable or unresectable STS in patients who are not candidates for chemotherapy. Results of this clinical trial support the further validation of RT and HT combinations in STS.

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