This is a nonrandomized Phase II pilot protocol to determine the feasibility, toxicity and disease control (local control, overall and progression-free survival) using hypofractionated preoperative radiation therapy in patients with primary localized soft tissue sarcomas (STS).

BACKGROUND OVERVIEW: Hypofractionation has several potential advantages over conventional radiation. First, the biological equivalent dose to the tumor is higher with hypofractionation than it is with conventional radiation. In between radiation treatments there is repair of the radiation damaged cancer cells (on a cell survival curve this region of repair is referred to as the "shoulder" of the curve). Some cell lines are better at repair than others. Sarcoma is often referred to as a "radioresistant" tumor, which means that sarcoma cell lines have a larger capacity for radiation repair than do other cell lines. A treatment that can deliver a high dose in fewer fractions can potentially overcome some of this repair. There is a concept in radiation known as "biologically equivalent dose" (BED) which states that a higher dose per fraction results in more tumor kill than a lower dose per fraction. For example, radiation delivered to a total of 60 Gy in three 20 Gy fractions is the equivalent of 150 Gy in 2 Gy fractions.

BACKGROUND RATIONALE: It is important to conduct this study because hypofractionation not only decreases treatment package time and cost of care, but it also potentially improves patient convenience and quality of life and could impact radiologic and pathologic variables in a positive way by leading to more tumor cell kill. This could potentially change the paradigm of the current management of STS of the extremity and chest-wall.

HYPOTHESIS: Preoperative hypofractionated radiation therapy for localized soft tissue sarcomas (STS) will result in local control and toxicity similar to conventional fractionation with less cost, more patient convenience and decreased overall treatment time.

TREATMENT: Image-guided radiation therapy is mandatory. PREOPERATIVE: (1) Either 3D conformal radiotherapy or intensity modulated radiation therapy (IMRT). (2) A prescription dose of 35 Gy in 5 fractions given every other day with at least 48 hours in between each fraction will be prescribed to cover 95% of the planning target volume. TREATMENT SCHEDULE: Treatments will have a minimum of a 48-hour interfraction interval. Treatments will be completed over 20 days maximum.

Inclusion Criteria:

• ≥ 18 years of age
• Core needle biopsy obtained
• Pathologic confirmation of primary soft tissue sarcoma of the upper or lower extremity or chest-wall.
• Stage I-III Soft Tissue Sarcoma of the extremity without evidence of metastatic disease
• Medically operable
• No prior radiotherapy to primary site or adjacent site that results in overlapping radiation fields.
• MRI obtained of the affected extremity or chest-wall
• CT chest acquired to assess distant disease
• Karnofsky Performance Status (KPS) 60 or above
• Informed consent obtained prior to study entry

Exclusion Criteria:

• Patients who have metastatic disease
• Pregnant women
• Women of childbearing potential and male participants must practice adequate contraception.
• Disease pathology other than sarcoma subtypes
• Patients with a history of metastatic disease from a primary other than sarcoma
• Patients who cannot undergo MRI as part of pre-treatment or treatment planning process
• STS of non-extremity or chest-wall regions
• Tumor size ≥ 20 cm maximal dimension

2 years