STARS (NCT 07265661): Surgical timing after preoperative hypofractionated radiotherapy for patients with primary localized soft tissue sarcoma of the extremity and trunk—A randomized phase 2 clinical trial.

Abstract

TPS11597 Background: Local management paradigm for localised soft tissue sarcoma of the extremities and trunk (ESTS) has remained relatively stable, due to the excellent outcomes associated with preoperative radiotherapy combined with limb-sparing surgery. Conventional regimens (50 Gy in 25 fractions) are effective but time-intensive and resource-demanding. Ultra-hypofractionated radiotherapy (HFRT) has emerged as a promising strategy, with comparable oncological outcomes, in preliminary retrospective analyses, prospective cohorts, and Phase II non-randomised trials. However, the optimal interval between HFRT and surgery remains undefined. Methods: STARS is a national, multicenter, phase II, randomized, non-inferiority trial promoted by a co-sponsorship between the Italian Sarcoma Group and the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (NCT07265661). Patients with localised, resectable ESTS scheduled for combined radiotherapy and surgery are randomized 1:1 to receive preoperative HFRT (30 Gy in 5 fractions) followed by surgery at either 1–2 weeks (Arm A) or 4–6 weeks (Arm B). Randomization is stratified by tumor size, depth, site, and comorbidities. The primary endpoint is the incidence of postoperative complications (Clavien–Dindo, any grade) within 90 days. Secondary endpoints include quality of life and patient satisfaction, oncologic outcomes (local recurrence, distant metastasis, disease-free and overall survival), pathological and radiological response, treatment-related toxicity, nutritional status, and economic impact. A concurrent observational cohort will capture outcomes of patients treated with standard approaches (surgery with/without standard radiotherapy). Statistical Design: A total of 142 patients (71 per arm) will be enrolled to test non-inferiority, assuming a 35% postoperative complication rate and a non-inferiority margin of 15% (one-sided α=0.05; power 80%). Approximately 30 additional patients are expected in the observational cohort. Significance: STARS is the first randomized trial specifically designed to address surgical timing following HFRT in ESTS. The study is conducted within a novel co-sponsorship framework involving a national academic tertiary cancer center (Fondazione IRCCS Istituto Nazionale dei Tumori) and the leading non-profit cooperative group for rare cancers in Italy (Italian Sarcoma Group), establishing a sustainable platform for high-quality clinical research in rare diseases. By defining the safest and most effective interval between HFRT and surgery, this trial aims to optimize perioperative outcomes while enabling a shorter, patient-centered, and resource-efficient treatment pathway, informing future standards of care and guideline recommendations for localised ESTS. Clinical trial information: NCT 07265661 .