SPRINT trial: Preoperative chemotherapy and IMRT SIB in locally advanced sarcoma.
Authors: Greto Daniela , Loi Mauro , Campanacci Domenico Andrea , Allegra Andrea Gaetano , Sacchetti Federico , Roselli Giuliana , Palomba Annarita , Becherini Carlotta , Muratori Francesco , Bonaparte Ilaria , Banini Marco , Meattini Icro , Livi Lorenzo 
Published: June 2023

e23548 Background: In Soft Tissue Sarcoma (STS) patients with high risk features, preoperative radiotherapy (RT) associated with anthracyclines-based chemotherapy is delivered to downstage the tumor and improve resectability, although at the expense of increased risk of skin toxicity and wound dehiscence that hinder further dose escalation. Modern IMRT may overcome this limitation due to precise dose modulation that allows selectively spare radiation-sensitive structure (skin) while increasing dose to selected target volumes. The aim of this study is to assess the safety and effectiveness of the addition of a preoperative IMRT boost to the potential sites of suboptimal resection in STS patients receiving neoadjuvant chemotherapy and RT. We report hereby the dosimetric and safety results from the first 5 patients enrolled in this trial. Methods: We designed a monocentric interventional single-arm Phase II study to investigate the use of preoperative chemotherapy and RT with Simultaneous Integrated Boost (SIB) in a prospective cohort of locally advanced STS patients eligible for surgery. Epirubicin 60 mg/m2 per day (days 1,2) plus Ifosfamide 3 g/m2 per day (days 1-3), repeated every 21 days, were administered up to three cycles. RT will be administered in 25 daily fractions to include the tumor and peritumoral tissue at risk of microscopic spread (PTV1) to a dose of 50 Gy (2Gy/fraction), with SIB intensification to the tumor/dissection plane interface (PTV2) to a dose of 60 Gy (2.4 Gy/fraction). Response evaluation will be performed by MRI at 4 weeks and on the surgical specimen. 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. Results: 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). Mean tumor volume 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 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) . At the time of this report, no Grade ≥3 acute skin toxicity was observed. All patients completed the associated treatment, one patient had a G2 anaemia after the first CT cycle and two patients developed Grade 3 neutropenia. Two patients underwent surgery with a radiological partial response (RECIST) and pathological complete response. No major wound complication was reported. Conclusions: 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.