NCT07501026

Preoperative Spatially Fractionated Radiation Therapy (SFRT) in Soft Tissue Sarcoma (neoSFRT-SARC)

A Phase II Prospective Study of Preoperative Spatially Fractionated Radiation Therapy (SFRT) in Soft Tissue Sarcoma (neoSFRT-SARC)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this prospective, single-arm, phase II trial is to evaluate whether a preoperative regimen combining spatially fractionated radiation therapy (SFRT) with subsequent surgery can improve outcomes in patients with large (≥5 cm) limb/trunk soft tissue sarcoma (STS). Currently, there is a lack of standardized SFRT-based protocols for operable or borderline-resectable large STS, and optimal dose-fractionation schedules, timing to surgery, differential efficacy by resectability status, and the induced systemic immune response remain undefined. Patients will receive 5 fractions of SFRT to the primary tumor, followed by definitive surgery. The main questions are: * Can this SFRT-first approach increase the 1-year disease-free survival (DFS) compared with historical controls? * What are the pathologic complete response (pCR) rate, overall survival (OS), and treatment-related safety profile? * What immune mechanisms are engaged by SFRT, as reflected by dynamic changes in peripheral immune cell subsets and cytokines? Participants will undergo SFRT, then surgery, with serial blood sampling for immune monitoring.

Detailed description

For localized STS, surgery combined with radiotherapy is the standard of care. Preoperative radiotherapy can reduce tumor volume, facilitate resection, and lower recurrence risk. However, two major challenges remain: (1) radioresistance-STS is generally radioresistant, especially in bulky tumors; pivotal studies (e.g., RTOG 0630) report pathologic complete response (pCR) rates below 20% with conventional fractionation; (2) limited local control in unresectable cases-historical data show 5-year local control below 10% for tumors \>10 cm treated with definitive radiotherapy alone. Spatially fractionated radiation therapy (SFRT) delivers high-dose peaks within the tumor while maintaining lower-dose valleys, creating a non-uniform dose distribution that may enhance tumor kill, potentially trigger systemic antitumor immunity, and spare adjacent normal tissues. Recent retrospective data from Mayo Clinic (2024) demonstrated that in advanced, unresectable sarcomas, SFRT followed by conventional external-beam radiotherapy achieved 1-year local control of 82% and symptom relief in 60%, with acceptable toxicity. These promising results support prospective evaluation of SFRT in the preoperative setting for operable or borderline-resectable large STS. Eligible patients will receive SFRT to the primary tumor in 5 fractions, followed by definitive surgery. The primary endpoint is 1-year disease-free survival (DFS). Secondary endpoints include pCR rate, overall survival (OS), and safety assessed by CTCAE v5.0. Exploratory objectives involve longitudinal monitoring of peripheral blood immune cell subsets (e.g., CD8⁺, CD4⁺, Treg cells) and cytokines (e.g., IFN-γ, TNF-α) to characterize SFRT-induced systemic immune modulation and identify potential biomarkers of response.

Conditions

• Sarcoma

Interventions

Type	Name	Description
RADIATION	SFRT	1. Preoperative SFRT: The prescribed dose is 20 Gy in 5 fractions, with lattice dose of 66.7Gy in 5 fractions. 2. Surgery: Approximately one week after completion of SFRT, tumor resectability is reassessed. Patients who achieve sufficient tumor response undergo definitive surgical resection. Those who remain unsuitable for surgery after SFRT will receive alternative treatment per standard of care. 3. Translational immune monitoring: Peripheral blood samples are collected at baseline, one week post-SFRT, and at 1, 3, 6, and 12 months post-treatment for exploratory analysis of immune cell subsets (e.g., CD8⁺ T cells) and cytokine profiles (e.g., IFN-γ, TNF-α), aimed at characterizing SFRT-induced systemic immune modulation.

Timeline

• Start date: 2026-03-16
• Primary completion: 2028-03-16
• Completion: 2029-03-16
• First posted: 2026-03-30
• Last updated: 2026-03-30

Locations

1 site across 1 country: China