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 theduration of the study

• For women of childbearing potential: use of highly effective contraception for atleast 1 month prior to screening and agreement to use such a method during studyparticipation and for an additional 52 weeks after the end of radiation.

• For males of reproductive potential: use of condoms or other methods to ensureeffective contraception with partner 52 weeks after radiation.

• Agreement to adhere to Lifestyle Considerations (as outlined in protocol) throughoutstudy 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, andshould 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, noevidence of distant metastases

• Patients must have clinically or radiographically evident measurable disease at theprimary 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 ofradiation therapy fields.

• Participants with a medical condition or social situation that, at the discretion ofthe principal investigator, would preclude them from completion of the trial.