This phase II trial studies the wound complication risk of shorter course, hypofractionated pre-surgery radiation therapy in treating patients with localized soft tissue sarcoma of the extremity of superficial trunk that can be removed by surgery. Hypofractionated 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. Shorter course hypofractionated pre surgery radiation therapy may be more convenient for patients with soft tissue sarcoma than a longer course of radiation therapy, and may result in fewer complications.

PRIMARY OBJECTIVES:

I. To determine, in patients with localized, resectable soft tissue sarcoma, whether there is a non-inferior major wound complication rate for patients receiving 42.75 Gy in 15 fractions over 3 weeks compared to historical controls who received 50 Gy in conventional fractionation over 5-6 weeks.

SECONDARY OBJECTIVES:

I. To determine whether local control rates among patients treated with 42.75 Gy in 15 fractions is similar to that observed in previous studies for patients treated with 50 Gy in conventional fractionation over 5-6 weeks.

II. To determine whether patterns of local relapse, relapse free survival, overall survival, or metastatic disease free survival for patients treated with 42.75 Gy in 15 fractions are similar to previously reported studies.

III. To determine where there is a difference in pathologic response in tumor specimens treated with 42.75 Gy in 15 fractions compared to previously reported rates of hyalinization, fibrosis, or necrosis.

IV. To explore quality of life, as measured by the Functional Assessment of Cancer Therapy-General (FACT-G), financial toxicity as measured by the Comprehensive Score for financial Toxicity (COST) Instrument, and patient reported outcomes, as measured by the Toronto Extremity Salvage Score (TESS), among individuals undergoing a shorter, hypofractionated course of pre-operative radiation therapy for soft tissue sarcoma of the extremity or superficial trunk.

V. To gather subjective data on patient treatment preferences and experiences among individuals undergoing a shorter, hypofractionated course of pre-operative radiation therapy for soft tissue sarcoma of the extremity or superficial trunk.

OUTLINE:

Patients receive hypofractionated radiation therapy in 15 daily fractions over 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-4 months for 2 years, every 6 months for 3 years, and then every year for up to 10 years.

Inclusion Criteria:

• Tumor located in the soft tissues of the extremities or superficial trunk
• Deemed a candidate for complete macroscopic resection of the primary sarcoma
• Histologically confirmed sarcoma arising in soft tissue
• Patient may have had excisional biopsy of all gross disease at an outside facility with positive or uncertain resection margins and still be eligible if the evaluating sarcoma surgeon in the participating institution recommends oncologic re-resection of the surgical bed to obtain negative margins after a course of neoadjuvant irradiation (a sandwich approach of marginal excision-->radiation therapy(RT)--> wide excision, as per our standard practice)
• No evidence of nodal or distant metastases as determined by clinical examination or any form of imaging
• Has provided written informed consent for participation in this trial
• Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less
• Life expectancy greater than 6 months
• Patients capable of childbearing are using adequate contraception
• Available for follow-up

Exclusion Criteria:

• Previous radiation therapy to the site of the sarcoma or area surrounding it such that it would be encompassed by the radiation field needed to treat the current sarcoma. In other words, treatment on this trial would require re-irradiation of tissues
• Patients with nodal or distant metastases
• Women who are pregnant