Spatially fractionated radiotherapy versus conventional radiotherapy in the treatment of soft tissue sarcoma: A multicenter, prospective, phase II, randomized controlled clinical trial protocol.

Abstract

Objective: Soft tissue sarcoma (STS) is a rare and highly heterogeneous malignancy. Conventional radiotherapy (CRT) often shows limited efficacy, especially in radioresistant subtypes, such as liposarcoma and fibrosarcoma, with local recurrence rates ranging from 10% to 30%. Spatially fractionated radiotherapy (SFRT), a technique that delivers non-uniform high-dose distributions, has shown promise in improving tumor control and potentially stimulating immune responses in preliminary studies.

Methods: This multicenter, prospective, randomized phase II trial aims to enroll 106 patients aged 18-70 years with pathologically confirmed STS and a minimum tumor diameter ≥5 cm. Participants will be randomized 1:1 into SFRT or CRT groups. CRT involves a uniform dose of 3.0 Gy per fraction over 15-20 fractions. SFRT employs a non-uniform dose distribution, supplementing CRT with high-dose spot irradiation of 8-15 Gy per fraction delivered for a total of 3-4 fractions. The primary endpoint was the objective response rate, and the secondary endpoints included local control, progression-free survival, and safety.

Discussion: This trial is the first randomized study to directly compare SFRT and CRT for STS. SFRT is expected to enhance tumor control and elicit immunomodulatory effects, particularly in radioresistant tumors. However, the potential acute toxicities and technical complexities warrant further evaluation. Future studies should investigate the synergistic potential of SFRT combined with immunotherapy.

Trial registration: The study was registered at ClinicalTrials.gov with the Identifier: NCT06980259 (Registered 12th May 2025).