Surgical Timing After Preoperative Hypofractionated Radiotherapy for Localized Extremity and Trunk Soft Tissue Sarcoma

Phase II, national, multicentric, prospective, randomized (1:1) non-inferiority trial with two parallel groups, incorporating a concurrent observational cohort of eligible non-randomized patients, designed to address critical knowledge gaps by prospectively evaluating the safety, efficacy, and feasibility of preoperative ultra-hypofractionated radiotherapy (HFRT) in patients with soft tissue sarcomas (STS) of the extremities and trunk.

Inclusion Criteria: * Voluntary written informed consent, with the ability to fully understand and effectively communicate, before performance of any study-related procedure not part of normal medical practice, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Age \> 18 years * Proven diagnosis of primary, resectable extremity/trunk wall STS with low-medium risk (Sarculator© predicted 10y-OS \> 60%) * Measurable disease criteria (RECIST 1.1 and CHOI) * ECOG: 0, 1 or 2 (if influenced by orthopedic condition and not by general status) * No major contraindication to the planned radiotherapy or surgical treatment * Active participation with adherence to requested treatment schedule and follow-up * Female subject will undergo a negative pregnancy test * Adequate bone marrow function (hemoglobin \> 9g/dL, Leukocytes \> 3000/mm³, platelets \> 100,000/mm³). Patients with plasma creatinine ≤ 1.6 mg/dL, transaminase (AST-SGOT, ALT-SGPT) ≤ 2.5 times the UNL; total bilirubin ≤ 1.5 time the UNL; alkaline phosphatase ≤ 2.5 times the UNL are acceptable. CRP, LDH, total protein and albumin must also be recorded. * HBV and HCV serologies must be performed prior to patient inclusion. If hepatitis B surface antigen (HBsAg) is positive, further evaluation is required to exclude active viral replication (i.e., testing for hepatitis B e antigen \[HBeAg\] and HBV DNA). If either of these markers is positive, study inclusion is not recommended. In such cases, prophylactic treatment with lamivudine may be considered at the investigator's discretion. If a potential participant tests positive for anti-HCV antibodies, active infection must be ruled out through a qualitative HCV PCR test. If PCR testing cannot be performed, or if it confirms active infection, the patient will not be eligible for the study. Patients must be HIV-seronegative, with a CD4+ T-cell count greater than 400/mm³. Individuals with clinically significant immunodeficiency-either congenital or acquired-are not eligible for enrollment Exclusion Criteria: * Age \< 18y * Soft tissue sarcomas (STS) originating at different sites (i.e., retroperitoneal, abdominal, pelvic, head and neck), gynecological sarcomas, as well as gastrointestinal stromal tumors (GISTs), desmoid-type fibromatosis and pediatric-type sarcomas (i.e., extraosseous Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, desmoplastic small round cell tumor) are excluded. * Recurrent or metastatic condition or previous whoop-surgery for sarcoma (incisional biopsies are allowed if performed 6 months before referral). * Unresectable tumors (with limb sparing surgery) * Diagnosed oncological condition in the 5 years before enrollment (exceptions: Gleason \