This research study will collect blood and tumor tissue samples from patients with soft tissue sarcoma to look at circulating tumor deoxyribonucleic acid (DNA). When tumor cells are damaged or die, DNA from the tumor cells are released into the blood stream as the cells break down. This is called circulating tumor DNA. Circulating tumor DNA is an important biomarker that may be used in cancer detection, prediction of treatment response, and disease monitoring.

Researchers are continually looking for ways to understand the biology of cancer such as sarcoma, and ways to improve cancer care and patient outcome.

Research has shown that changes in some genes and/or proteins, called biomarkers, may be important indicators for certain cancers and response to treatments. Genes are molecules made up of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). DNA contain instructions for the development and functioning of the cells in the body and are passed down from parent to child. RNA is involved with producing proteins in the body. Further research is needed to better understand the changes found in cancer cells and what this means for certain treatments.

Circulating tumor DNA is an important biomarker that may be used in cancer detection, prediction of treatment response and disease monitoring. When tumor cells are damaged or die, DNA from the tumor cells are released into the blood stream as the cells break down. This is called circulating tumor DNA. Researchers are looking for better ways to detect circulating tumor DNA so that it can be studied.

The purpose of this study is to determine how feasible it is to detect circulating tumor DNA in blood samples of soft tissue sarcoma patients and whether there is a connection between circulating tumor DNA and the likelihood of patients' disease coming back after they receive treatment. To do this, blood and tumor tissue samples will be collected from participants and will undergo DNA testing (reading the contents of their DNA, called sequencing). The results of the DNA testing in the blood samples will be compared with the results from DNA testing that will also be done on tumor tissue. The results will also be compared with participant's response to their treatment, recurrence, and/or long term survival.

Inclusion Criteria:

• Patients must have histologically confirmed high-risk extremity or retroperitoneal liposarcoma, leiomyosarcoma and undifferentiated pleomorphic sarcoma.
• Patients must have archival tissue from the diagnostic biopsy available.
• Deemed appropriate for preoperative or postoperative radiotherapy and curative surgery following patient assessment by radiation oncologist and surgical oncologist.
• Age 18 years or older.
• Eastern Cooperative Group (ECOG) performance status ≤ 2
• Ability to understand and willing to sign a written informed consent document and comply with study requirements.

Exclusion Criteria:

• Patients with benign histology
• Patients with prior malignancy within previous 5 years or concurrent malignancy other than adequately treated basal cell carcinoma of skin or carcinoma in-situ of cervix.
• Patients with planned neo-adjuvant chemotherapy.
• Patients with regional nodal disease or unequivocal metastases
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.