Testing Short-Course Radiation Versus Standard-Course Radiation for Soft Tissue Sarcomas That Need Surgery and Radiation

PRIMARY OBJECTIVE: I. To evaluate whether the incidence of local tumor recurrence at 2-years after randomization with short-course radiation is non-inferior to standard-course radiation among participants with high-risk, resectable soft tissue sarcoma. SECONDARY OBJECTIVES: I. To estimate and compare between arms the incidence of acute wound complications. II. To estimate and compare between arms the incidence of late-term complications associated with radiation at 2-years post-surgery. III. To estimate and compare between arms changes in physician-assessed functional outcome from pre-randomization to 12 and 24 months post surgery using the Musculoskeletal Tumor Society Scoring system. IV. To estimate and compare between arms overall survival, progression-free survival, and distant-metastasis-free survival measured from randomization. EXPLORATORY OBJECTIVES: I. To estimate and compare between arms the incidence of local tumor recurrence at 2 years using a per-protocol analysis. II. To estimate and compare between arms the incidence of delayed wound healing. III. To report the type of surgical resection by treatment arm, including limb-salvage versus amputation and margin status (R0, R1, or R2). IV. To describe the use of supportive therapy medications given with radiation therapy separately by treatment arm. V. To describe the use of adjuvant therapy post-surgery separately by treatment arm. BANKING OBJECTIVE: I. To bank tissue specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients undergo RT-25 with 3D CRT or IMRT once daily (QD) for up to 5 fractions per week for 25 fractions over a minimum of 32 calendar days and maximum of 49 days in the absence of disease progression or unacceptable toxicity. Starting 22-56 calendar days after radiation, patients undergo surgical resection. Additionally, patients undergo magnetic resonance imaging (MRI), computed tomography (CT), and blood sample collection throughout the study. ARM 2: Patients undergo UHRT-5 with 3D CRT or IMRT QD for up to 5 fractions per week for 5 fractions over a minimum of 5 calendar days and maximum of 14 days in the absence of disease progression or unacceptable toxicity. Starting 22-56 calendar days after radiation, patients undergo surgical resection. Additionally, patients undergo MRI, CT, and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 4 months, every 6 months after surgery for up to 5 years, and then annually for up to 10 years after randomization.