(P 546) PRELIMINARY CLINICAL RESULTS OF AN ONGOING PHASE II TRIAL: SPRINT (SARCOMA PREOPERATIVE RADIATION WITH SIMULTANEOUS INTEGRATED BOOST)

Objective: The treatment of localised Soft Tissue Sarcoma (STS) is surgery combined with radiotherapy (RT). Intralesional or Marginal Surgery (R+) are predictive of local recurrence and worse survival. A planned R+ surgery may result from proximity of critical structures to preserve the functionality. In locally advanced STS, preoperative RT is used to downstage the tumor and improve resectability, with an increased risk of wound dehiscence compared to postoperative RT. Modern IMRT may overcome this risk thanks to precise dose modulation that allows selectively spare radiation-sensitive structure (skin) while increasing dose to selected target volumes. SPRINT(Sarcoma Preoperative Radiation with simultaneous INTegrated boost) study was designed to assess the safety and effectiveness of the addition of a preoperative IMRT boost to the potential sites of R+ in STS patients receiving neoadjuvant RT. Here are the early clinical outcomes of the first enrolled patients.

Methods: SPRINT (NCT05761054) is a prospective monocentric single-arm phase II study enrolling locally advanced STS patients eligible for surgery. RT is administered in 25 daily fractions to the MRI-based GTV and peritumoral tissue at risk of microscopic spread (CTV1) to a dose of 50 Gy (2Gy/fraction), with a simultaneous integrated boost to the tumor/dissection plane interface (CTV2) to a dose of 60 Gy (2.4 Gy/fraction). A margin of 0.5 cm is applied to both CTV to obtain PTV1 and PTV2. Concurrent anthracyclines-based chemotherapy is allowed up to 3 cycles. Primary endpoint is the R0 resection rate. Secondary endpoints include pathologic complete response rate, objective response rate, OS, local and distant PFS, 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 shown 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%.

Results: Five patients were included, with a mean age of 47 years. Tumor was in the limbs and in the trunk in respectively 4 and 1 patient. Concurrent chemotherapy was performed in 2 patients. Epirubicin and ifosfamide-based chemotherapy was administered in both cases. 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). The NVB was overlapping the PTV2 in all cases, but Dmax was below 66 Gy. All patients underwent surgery with a R0 resection. Two patients had a pathological complete response. One patient had wound complication requiring VAC therapy.

Conclusion: Planning goals of the first 5 treated patients are achieved in most cases. Preliminary results show a promising tumor response rate.