A parallel-group randomized pilot trial at a single institution (Duke University) on the effect of postoperative hyperbaric oxygen therapy on wound healing in patients with soft tissue sarcoma undergoing surgical resection with neo-adjuvant radiation therapy.. Participants will be allocated to either the treatment group (HBOT) or control (standard of care) by computer-generated randomization, stratified by tumor size (≤10cm and >10cm). An unequal randomization of 2:1 will be utilized to provide experience prescribing HBOT to more patients.

Patients with a primary diagnosis of soft tissue sarcoma of the lower extremities undergoing treatment with neo-adjuvant radiation therapy and surgical resection will be screened for eligibility. All participants will receive pre-operative radiation treatment per standard of care and will undergo surgical excision as planned and performed by one of the surgical oncologists at our center. Participants randomized to the treatment group will be scheduled for 7-10 HBO treatments within 7-10 days of surgery. All participants will be scheduled for follow-up visits with their surgical oncologist at the following post-operative time points: 3, 6, 12, and 24-weeks (+/- 14 days). Follow up for the purposes of this study will continue up to 6 months from the time of surgery.

Inclusion Criteria:

1. Males and females within the ages of 18-85
2. Diagnosis of soft tissue sarcoma that has been histologically confirmed by an approved reference pathologist
3. Sarcoma of lower extremity location
4. Treatment plan that includes neo-adjuvant radiation therapy followed by surgical resection
5. Expected primary wound closure performed at the time at surgery
6. Any disease stage
7. Any tumor grade
8. Any histologic subtype
9. First or recurrent presentations
10. No vascular invasion or resection/repair/reconstruction that results in decreased perfusion of the extremity
11. No history of radiation therapy to the tumor and/or surgical area prior to the current treatment being studied
12. Must be able to comply with follow up visits
13. Must be able to provide own consent

Exclusion Criteria:

1. Patients under the age of 18, or over the age of 85.
2. Treatment plan that doesn't include neo-adjuvant radiation and surgical excision
3. Sarcoma location other than lower extremity
4. History of radiation therapy to the tumor and/or surgical area prior to the current treatment being studied
5. High dose steroid therapy (defined as >5mg prednisone, or equivalent, daily)
6. Active treatment with chemotherapy
7. Inability of the patient to provide informed consent (i.e. dementia, cognitive impairment, non-English speakers)
8. Plan for post operative radiation therapy
9. Vascular invasion or resection/repair/reconstruction that results in decreased perfusion of the extremity
10. Vascular disease resulting in clinically apparent compromise in blood flow to the treatment extremity (i.e. peripheral vascular disease with diminished pulses, venous insufficiency with clinical evidence of vascular congestion)
11. Actively uncontrolled diabetes mellitus (documentation of history of diabetes mellitus with A1c>8)
12. Active deep vein thrombosis in the treatment extremity
13. Inability to comply with follow up visits
14. Pregnant females (women of childbearing potential must have a negative serum pregnancy test prior to enrollment)