SCOPES-II: short course of preoperative radiotherapy in head and neck, trunk and extremity soft tissue sarcomas - study protocol for a second randomised phase II clinical trial.

INTRODUCTION: Soft tissue sarcomas (STS) are rare malignant tumours typically treated with surgery in combination with radiotherapy and/or chemotherapy. Conventional preoperative radiotherapy (25×2 Gy) prolongs treatment duration up to 3-5 months, which can substantially have an impact on the patient's burden. Moderate hypofractionated schedules (14-15×2.85-3 Gy) have shown comparable oncological outcomes and toxicity profiles to conventional treatment. Data on ultra-hypofractionated regimens, such as 5×6 Gy, suggest comparable outcomes. The SCOPES-II trial is designed to evaluate and compare a moderately hypofractionated radiotherapy regimen (14×3 Gy) with an ultra-hypofractionated schedule (5×6 Gy) in adults diagnosed with STS of intermediate or high histological grade. METHODS AND ANALYSIS: This international, multicentre, randomised phase II trial will include 150 adult patients with localised STS showing intermediate or high tumour grade, arising in the head and neck region, trunk, chest wall or limbs. Patients assigned to arm A will receive preoperative radiotherapy delivered as 14 fractions of 3 Gy, whereas those in arm B will undergo treatment consisting of 5 fractions of 6 Gy. In both treatment arms, surgical resection is planned approximately 6 to 8 weeks following completion of radiotherapy. The primary endpoint is the rate of postoperative wound-related complications occurring within 120 days after surgery. Secondary objectives comprise assessment of oncological efficacy, including local control and the development of distant disease, evaluation of late radiation-associated toxicities, patient-reported Health-Related Quality of Life (HRQoL) and an analysis of cost-effectiveness. ETHICS AND DISSEMINATION: Ethical approval for this trial has been obtained from the relevant Medical Ethics Committees (METc) in both the Netherlands (Medisch-Ethische Toetsingscommissie NedMec NL009842) and Poland (43/2026). Written informed consent will be obtained from all participants before inclusion in the study. The findings of this trial will be shared through publication in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT07071727.