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

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.

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.

• Measurable lesion (per RECIST 1.1/Choi criteria: longest diameter >1.5 cm, or >1 cm with two measurable perpendicular diameters).

• ECOG performance status ≤2. 7. Expected survival ≥3 months. 8. Normal liver, kidney, lung, and cardiac function, with tolerance for treatment.

• Patients of childbearing potential agree to use reliable contraception during treatment and for one year thereafter.

• 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.