Spatially Fractionated Radiotherapy Versus Conventional Radiotherapy in the Treatment of Soft Tissue Sarcoma

Shandong Cancer Hospital and Institute106 enrolled

Overview

This study is a multicenter, prospective, randomized controlled phase II clinical trial designed to evaluate the efficacy and safety of Spatially Fractionated Radiation Therapy (SFRT) compared to Conventional Radiation Therapy (CRT) in the treatment of soft tissue sarcoma (STS, minimum tumor diameter ≥5 cm). A total of 106 patients were enrolled and randomized in a 1:1 ratio. The primary endpoint is the objective response rate (ORR) of the target lesion at 3, 6, 9, and 12 months post-radiotherapy, assessed using RECIST 1.1 and Choi criteria. Secondary endpoints include the 1-year local control rate (LC) of the target lesion, progression-free survival (PFS), safety (per CTCAE v5.0), and quality of life (QoL, assessed by EORTC QLQ-C30). CRT is delivered at 3.0 Gy per fraction for a total of 15-20 fractions. SFRT comprises CRT at 3.0 Gy per fraction for 15-20 fractions, augmented by weekly high-dose vertices of 8-15 Gy per fraction for 3-4 fractions, aiming to enhance tumor control and potentially stimulate immune responses. This study is a multicenter, prospective, randomized controlled phase II clinical trial designed to evaluate the efficacy and safety of Spatially Fractionated Radiation Therapy (SFRT) compared to Conventional Radiation Therapy (CRT) in the treatment of soft tissue sarcoma (STS, minimum tumor diameter ≥5 cm). A total of 106 patients were enrolled and randomized in a 1:1 ratio. The primary endpoint is the objective response rate (ORR) of the target lesion at 3, 6, 9, and 12 months post-radiotherapy, assessed using RECIST 1.1 and Choi criteria. Secondary endpoints include the 1-year local control rate (LC) of the target lesion, progression-free survival (PFS), safety (per CTCAE v5.0). CRT is delivered at 3.0 Gy per fraction for a total of 15-20 fractions. SFRT comprises CRT at 3.0 Gy per fraction for 15-20 fractions, augmented by weekly high-dose vertices of 8-15 Gy per fraction for 3-4 fractions, aiming to enhance tumor control and potentially stimulate immune responses.

This study is a multicenter, prospective, randomized controlled phase II clinical trial designed to systematically compare the efficacy and safety of Spatially Fractionated Radiation Therapy (SFRT) versus Conventional Radiation Therapy (CRT) in the treatment of soft tissue sarcoma (STS, minimum tumor diameter ≥5 cm). STS is a malignant tumor with low radiosensitivity, and CRT yields limited objective response rates (ORR) and local control rates (LC). The study employs Intensity-Modulated Radiation Therapy (IMRT), Intensity-Modulated Proton Therapy (IMPT), or Volumetric Modulated Arc Therapy (VMAT) techniques. CRT is administered at 3.0 Gy per fraction for a total of 15-20 fractions. SFRT builds on CRT at 3.0 Gy per fraction for 15-20 fractions, supplemented by weekly high-dose vertices of 8-15 Gy per fraction for 3-4 fractions, aiming to enhance tumor control and stimulate potential immune responses. A total of 106 patients will be enrolled and randomized 1:1 into the SFRT and CRT arms (53 patients per arm). The primary endpoint is the ORR of the target lesion at 3, 6, 9, and 12 months post-radiotherapy, assessed using RECIST 1.1 and Choi criteria. Secondary endpoints include the 1-year LC of the target lesion, progression-free survival (PFS), safety (per CTCAE v5.0). Eligibility criteria include patients aged 18-70 years, ECOG performance status ≤2, and an expected survival of ≥3 months, excluding those with secondary primary tumors or severe organ dysfunction. Comprehensive baseline assessments (imaging, pathology, and laboratory tests) are conducted before treatment. Toxicity is monitored weekly during treatment, with ≥grade 3 toxicities prompting treatment suspension. Efficacy evaluations are performed at 3, 6, 9, and 12 months post-radiotherapy, with follow-up scheduled every 3 months in the first year, every 6 months in the second year, and annually thereafter. Statistical analysis is based on a one-sided α=0.05 and β=0.8, anticipating an ORR of 40% for SFRT compared to 15% for CRT. Through its multicenter design and rigorous evaluation, this study aims to validate whether SFRT can improve ORR in STS, providing scientific evidence to optimize radiotherapy strategies, enhance patient prognosis, and improve QoL. Additionally, it seeks to offer insights into the treatment of other radioresistant tumors. This study is a multicenter, prospective, randomized controlled phase II clinical trial designed to systematically compare the efficacy and safety of Spatially Fractionated Radiation Therapy (SFRT) versus Conventional Radiation Therapy (CRT) in the treatment of soft tissue sarcoma (STS, minimum tumor diameter ≥5 cm). STS is a malignant tumor with low radiosensitivity, and CRT yields limited objective response rates (ORR) and local control rates (LC). The study employs Intensity-Modulated Radiation Therapy (IMRT), Intensity-Modulated Proton Therapy (IMPT), or Volumetric Modulated Arc Therapy (VMAT) techniques. CRT is administered at 3.0 Gy per fraction for a total of 15-20 fractions. SFRT builds on CRT at 3.0 Gy per fraction for 15-20 fractions, supplemented by weekly high-dose vertices of 8-15 Gy per fraction for 3-4 fractions, aiming to enhance tumor control and stimulate potential immune responses. A total of 106 patients will be enrolled and randomized 1:1 into the SFRT and CRT arms (53 patients per arm). The primary endpoint is the ORR of the target lesion at 3, 6, 9, and 12 months post-radiotherapy, assessed using RECIST 1.1 and Choi criteria. Secondary endpoints include the 1-year LC of the target lesion, progression-free survival (PFS), safety (per CTCAE v5.0). Eligibility criteria include patients aged 18-70 years, ECOG performance status ≤2, and an expected survival of ≥3 months, excluding those with secondary primary tumors or severe organ dysfunction. Comprehensive baseline assessments (imaging, pathology, and laboratory tests) are conducted before treatment. Toxicity is monitored weekly during treatment, with ≥grade 3 toxicities prompting treatment suspension. Efficacy evaluations are performed at 3, 6, 9, and 12 months post-radiotherapy, with follow-up scheduled every 3 months in the first year, every 6 months in the second year, and annually thereafter. Statistical analysis is based on a one-sided α=0.05 and β=0.8, anticipating an ORR of 40% for SFRT compared to 15% for CRT. Through its multicenter design and rigorous evaluation, this study aims to validate whether SFRT can improve ORR in STS, providing scientific evidence to optimize radiotherapy strategies, enhance patient prognosis, and improve QoL. Additionally, it seeks to offer insights into the treatment of other radioresistant tumors.

Interventions

Spatially Fractionated RadiotherapyRADIATION

SFRT builds on CRT, administered at 3.0 Gy per fraction for 15-20 fractions, with the addition of weekly high-dose vertices of 8-15 Gy per fraction for 3-4 fractions. It employs Intensity-Modulated Radiation Therapy (IMRT), Intensity-Modulated Proton Therapy (IMPT), or Volumetric Modulated Arc Therapy (VMAT) to create a grid-like pattern of alternating high- and low-dose regions. Target volume delineation includes the gross tumor volume (GTV), clinical target volume (CTV, expanded 0.5-1.0 cm from GTV), and planning target volume (PTV, expanded 1.0 cm from CTV). Prior to each treatment session, cone-beam CT (CBCT) or kilovoltage cone-beam CT (kV-CBCT) is used for Image-Guided Radiation Therapy (IGRT) to verify patient positioning.

Conventional RadiotherapyRADIATION

CRT is delivered at 3.0 Gy per fraction for a total of 15-20 fractions, utilizing Intensity-Modulated Radiation Therapy (IMRT) or Intensity-Modulated Proton Therapy (IMPT) techniques, ensuring a target volume dose coverage of at least 90%. Target volume delineation includes the gross tumor volume (GTV), clinical target volume (CTV, expanded 0.5-1.0 cm from GTV), and planning target volume (PTV, expanded 1.0 cm from CTV). Prior to each treatment session, cone-beam CT (CBCT) or kilovoltage cone-beam CT (kV-CBCT) is used for Image-Guided Radiation Therapy (IGRT) to verify patient positioning.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 1\. Age 18-70 years, irrespective of gender. 2. Pathologically or clinically confirmed diagnosis of soft tissue sarcoma. 3. Minimum tumor diameter ≥5 cm. 4. Receiving systemic treatment as per multidisciplinary team (MDT) recommendations. 5\. Measurable lesion (per RECIST 1.1/Choi criteria: longest diameter \>1.5 cm, or \>1 cm with two measurable perpendicular diameters). 6\. ECOG performance status ≤2. 7. Expected survival ≥3 months. 8. Normal liver, kidney, lung, and cardiac function, with tolerance for treatment. 9\. Patients of childbearing potential agree to use reliable contraception during treatment and for one year thereafter. 10\. Voluntary provision of signed informed consent. Exclusion Criteria: * (1) Patients with a second primary malignancy. (2) Diagnosis of aggressive fibromatosis or rhabdomyosarcoma. (3) Prior radiotherapy to the target lesion. (4) Tumor unsuitable for radiotherapy. (5) Severe liver, kidney, lung, or cardiac dysfunction, precluding tolerance to systemic therapy or radiotherapy. (6) Other severe medical conditions that may impact the study (e.g., uncontrolled diabetes, gastric ulcers, or other serious cardiopulmonary diseases). (7) Severe or uncontrolled infections, or active autoimmune diseases. (8) Clinically evident central nervous system dysfunction. (9) Pregnant or lactating women, or women of childbearing potential not using contraception. (10) Other conditions deemed unsuitable for participation by the investigator.

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

The objective response rate (ORR) is defined as the proportion of patients with soft tissue sarcoma target lesions achieving complete response (CR) or partial response (PR) at 3, 6, 9, and 12 months post-radiotherapy, evaluated according to RECIST 1.1 and Choi criteria. Per RECIST 1.1, CR is defined as the complete disappearance of all target lesions, and PR is defined as a ≥30% reduction in the sum of the diameters of target lesions. Per Choi criteria, CR is defined as the complete disappearance of all target lesions, and PR is defined as a ≥10% reduction in the sum of the diameters of target lesions or a ≥15% decrease in tumor density (Hounsfield Units, HU) on CT scans.

Time frame: 3、6、9、12months

Secondary Outcomes

Safety Assessment

Adverse events (e.g., skin reactions, tissue fibrosis, organ dysfunction) are monitored during treatment and follow-up in accordance with the CTCAE v5.0 criteria.

Time frame: 1 year

Local Control Rate（LC)

The local control rate (LC) is defined as the proportion of patients with no progression of the radiotherapy target lesion (i.e., no local recurrence or tumor enlargement, evaluated according to RECIST 1.1 criteria) one year after radiotherapy.

Time frame: 1year

Progression-Free Survival （PFS)

Progression-free survival (PFS) is defined as the time from the start of radiotherapy to either progression of the target lesion (assessed per RECIST 1.1 criteria) or patient death from any cause, whichever occurs first.