Habitat Escalated Adaptive Therapy (HEAT), With Neoadjuvant Radiation for Soft Tissue Sarcoma

Inclusion Criteria: * Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * For women of childbearing potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 52 weeks after the end of radiation. * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner 52 weeks after radiation. * Agreement to adhere to Lifestyle Considerations (as outlined in protocol) throughout study duration. * Pathologically (histologically or cytologically) proven diagnosis of high-grade (grade 2 or 3) Soft Tissue Sarcoma (STS) of the deep trunk and/or extremity. Clinical evidence should be documented, and may consist of pathology or imaging, and should be sufficient to estimate the size of the primary (for T stage) * Primary site deemed resectable prior to the start of trial * American Joint Committee on Cancer (AJCC) 8th edition staging T1-4 N0 M0, no evidence of distant metastases * Patients must have clinically or radiographically evident measurable disease at the primary site. * Pre-Radiation Therapy (RT) MRI within 4 weeks of the start of RT. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 3. * Deemed a surgical candidate * Participant agrees to blood and plasma preservation for future analysis. Exclusion Criteria: * Contraindications to an MRI * Positive urine pregnancy test * Gross total excision of primary STS, including an unplanned excision * Superficial sarcoma located primarily in the subcutaneous or cutaneous tissue * Prior radiation to the region of the study cancer that would result in overlap of radiation therapy fields. * Participants with a medical condition or social situation that, at the discretion of the principal investigator, would preclude them from completion of the trial.