Neoadjuvant radiotherapy to 50 Gy in 25 fractions is delivered in operable Soft Tissue Sarcoma (STS) patients to downstage the tumor and improve resectability, although at the expense of increased risk of wound dehiscence. Nonetheless, clear margin resection (R0) may not be achieved in tumors located in proximity of critical structures such as the neurovascular bundle (NVB), resulting in impaired local control. The aim of this study is to increase R0 rate through addition of an IMRT boost to the potential sites of suboptimal resection in STS patients receiving neoadjuvant RT. We report hereby the dosimetric results and safety results from the first 5 patients enrolled in this trial. We designed a prospective monocentric interventional single-arm Phase II study enrolling locally advanced STS eligible for surgery. RT is administered in 25 daily fractions to include the MRI-based Gross Tumor Volume (GTV) and peritumoral tissue at risk of microscopic spread (CTV1) to a dose of 50 Gy (2Gy/fraction), with SIB (Simultaneous Integrated Boost) intensification to the tumor/dissection plane interface (CTV2) to a dose of 60 Gy (2.4 Gy/fraction). CTV2 delineation is approved by both a Radiation Oncologist and Surgeon. A margin of 0.5 cm is applied to both CTV to obtain PTV1 and PTV2. Concurrent anthracyclines-based chemotherapy (ChT) is allowed up to 3 cycles. Primary endpoint is R0 resection rate. Secondary endpoints include pathologic complete response rate, objective response rate, overall survival, local and distant progression-free survival, acute and chronic toxicity rate. To assess an increase in R0 rate from 81% to 97% assuming β = 80% e α = 0.05, 33 patients will be included. Dose constraints are summarized in Table1. At least 95% of the PTV1 and PTV2 should be covered by 95% the prescription dose up to a maximum allowed dose of 107%. Five patients were included. Tumor was located in the limbs and in the trunk in respectively 4 and 1 patient. Mean age was 47 years (range: 19-67). Concurrent chemotherapy was performed in 2 patients. Mean GTV size was 228.6 cm3 (range: 59.8-314.5). Mean PTV coverage by the 95% of the dose prescription was 98% (95-100) and 97% (95-100) in PTV1 and PTV2, respectively. Mean PTV1 and PTV2 Dmax were 61.6 Gy (range: 59-63) and 64.1 Gy (range:63-66), in both cases below the 107% threshold. Mean Bone Dmax was 55 Gy (56.6-61.8 Gy). Dmax to the skin corridor exceeded 20 Gy in 1 patient (range 12.5-58.1). While the NVB was overlapping the PTV2 in all cases, Dmax was below 66 Gy. At the time of this report, no Grade ≥3 acute skin toxicity was observed. Two patients underwent surgery with a radiological partial response (RECIST) and pathological complete response. No major wound complication was reported. Planning goals of the first 5 enrolled patients are achieved in most cases. Preliminary results show a benign safety profile and promising tumor response rate.