• Leiomyosarcoma (LMS) is one of the more common soft tissue sarcomas (STS).
• Patients presenting with large, high-grade, localized LMS are at significant risk of developing metastasis following curative surgery.
• Clinical trials of neoadjuvant or adjuvant anthracycline and ifosfamide have suggested that patients with localized STS who are at high-risk of metastasis may benefit from chemotherapy, but the magnitude of benefit in unselected patient population is relatively small.
• Currently, patient age, and tumor size and grade are used to assess risk of metastases and survival
• Studies evaluating tumor response by imaging and histopathology have not established correlation between tumor characteristics as biomarkers for risk of metastasis or sarcoma recurrence.
• Circulating tumor DNA (ctDNA) is present in blood of patients with advanced/metastatic LMS and may serve as biomarker of tumor response to chemotherapy. Blood samples will be collected prior to, during and after chemotherapy and analyzed for ctDNA and for mutations in genes that are associated with increased risk of developing sarcoma. Tumor tissue will be collected and analyzed for changes in genes. Digital images of the sarcoma from CT or MRI scans obtained during treatment will be obtained for advanced radiomic analysis. Patients will be followed for 2 years after study entry for signs of sarcoma recurrence.
• A biomarker of tumor response and patient survival benefit from chemotherapy early in the course of chemotherapy would be of significant impact in treatment planning.

Inclusion Criteria:

• Patients with localized leiomyosarcoma (LMS) of extremity, body wall or retroperitoneum
• Grade 2 or 3, or high-grade LMS
• Tumor size >5 cm in greatest dimension
• Primary tumor amenable to complete resection
• There is no age requirement
• Participant agrees to receive neoadjuvant doxorubicin and ifosfamide combination chemotherapy
• If pre-operative radiation is administered, it must be administered after chemotherapy. Post-operative radiation may be administered
• Archival tumor tissue (either frozen sample, tissue block containing tumor, or minimum of 4 unstained slides and 1 H&E stained slide) from diagnostic or pre-treatment biopsy available for study research

Patients who have been diagnosed with grade 2 or 3, high-grade leiomyosarcoma who have agreed to receive neoadjuvant doxorubicin and ifosfamide combination chemotherapy where the primary tumor is amenable to complete resection

We will share deidentified genetic data on the NIH site, and deidentified imaging data will be shared with the lab at Columbia University. We are not sharing patient identities.