This clinical trial compares the effect of short-course ultrahypofractionated radiation therapy over 5 days (UHRT-5) to standard-course radiation therapy over 25 days (RT-25) in treating patients with soft tissue sarcomas of the extremities that may be primary or that may have come back to nearby tissue or lymph nodes after a period of improvement (locally recurrent) and that can be removed by surgery (resectable). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. 3-dimensional (3D) conformal radiation therapy (CRT) uses a computer to create a 3D picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. Intensity-modulated radiation therapy (IMRT) is a type of 3D radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Standard-course (fractionated) radiation divides the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. Ultrahypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving UHRT-5 may be as effective as RT-25 in treating patients with primary or locally recurrent soft tissue sarcomas of the extremities that are resectable. It may also improve quality of life by requiring fewer treatments.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
296
Undergo RT-25 with 3D-CRT
Undergo UHRT-5 with 3D CRT
Undergo blood sample collection
Undergo CT
Undergo RT-25 with IMRT
Undergo UHRT-5 with IMRT
Undergo MRI
Undergo surgical resection
Local tumor recurrence rate
Cumulative incidence of local tumor recurrence will be estimated non-parametrically with death from any cause analyzed as a competing risk. 2-year estimates of local tumor recurrence and standard errors will be calculated and used to calculate a one-sided 95% confidence internal for the difference in 2-year local tumor recurrence rates.
Time frame: At 2 years
Incidence of acute wound complications
Will be estimated in each arm with 95% exact confidence intervals and compared using Fisher's exact test.
Time frame: Up to 4 months after surgery
Incidence of late-term complications associated with radiation
Will be estimated in each arm with 95% exact confidence intervals and compared using Fisher's exact test.
Time frame: Up to 2 years post-surgery
Changes in physician-assessed functional outcome
Will be evaluated using the Musculoskeletal Tumor Society Scoring system.
Time frame: From pre-randomization up to 24 months post-surgery
Overall survival
Will be estimated in each arm and compared using log-rank tests.
Time frame: From randomization up to 10 years
Progression-free survival
Will be estimated in each arm and compared using log-rank tests.
Time frame: From randomization up to 10 years
Distant-metastasis-free survival
Cumulative incidence will be estimated non-parametrically in each arm and compared using Gray's test.
Time frame: From randomization up to 10 years
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