Currently, the effectiveness and safety of preoperative hypo-fractionated radiotherapy in treating extremity soft tissue sarcomas remain inconclusive, warranting further investigation. Optimizing the neoadjuvant radiotherapy approach, including fractionation schedules and the interval between radiotherapy and surgery, is crucial to enhancing clinical efficacy while ensuring safety. This study proposes a multicenter, prospective, single-arm clinical trial utilizing preoperative SBRT for patients with high-grade extremity STS, tumors larger than 5 cm, or cases where achieving safe surgical margins is challenging due to involvement of surrounding blood vessels or nerves. The trial aims to preliminarily assess the impact of preoperative SBRT followed by radical surgery on surgical safety, quality of life, and tumor control in these patients.

The effectiveness and safety of preoperative hypo-fractionated radiotherapy in treating extremity soft tissue sarcomas remain inconclusive, warranting further investigation. Optimizing the neoadjuvant radiotherapy approach, including fractionation schedules and the interval between radiotherapy and surgery, is crucial to enhancing clinical efficacy while ensuring safety. This study proposes a multicenter, prospective, single-arm clinical trial utilizing preoperative SBRT for patients with high-grade extremity STS, tumors larger than 5 cm, or cases where achieving safe surgical margins is challenging due to involvement of surrounding blood vessels or nerves. The trial aims to preliminarily assess the impact of preoperative SBRT followed by radical surgery on surgical safety, quality of life, and tumor control in these patients.

Inclusion Criteria:

1. Aged ≥18 years;
2. Confirmed diagnosis of soft tissue sarcomas;
3. Highly malignant soft tissue sarcomas;
4. Not received surgery, chemotherapy or other antitumor therapy;
5. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1;
6. Signed informed consent;
7. Willing to provide tissue from an excisional biopsy of a tumor lesion，willing to provide blood sample before and after treatment;

Exclusion Criteria:

1. Patients with soft tissue sarcoma of extremities with shallow tumor location, small size, low grade pathology and operable surgical resection;
2. Distant metastasis;
3. Received surgery or chemotherapy or other antitumor therapy;
4. Previously participated in other clinical trials;
5. History of severe allergies, patients with allergic conditions, such as contrast agent allergy;
6. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
7. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy;
8. Active infection requiring systemic therapy;
9. Known psychiatric or substance abuse disorders ;
10. Pregnant or breastfeeding;
11. Known history of human immunodeficiency virus (HIV: HIV 1/2 antibodies);
12. Received a live vaccine within 30 days before radiotherapy.
13. Unable to lie flat.