Short Course Radiation Treatment for Patients With Primary or Locally Recurrent Retroperitoneal Sarcoma Prior to Surgery

Inclusion Criteria:

* Participants must have a histologically confirmed STS of the retroperitoneal space or infra-peritoneal spaces of pelvis
* Participant must have radiologically measurable disease (RECIST 1.1), as confirmed by abdomino-pelvic CT or MRI
* Participant must have primary, locally recurrent, or metastatic disease requiring treatment of the retroperitoneal mass
* Tumor must be suitable for radiotherapy and surgery based on pre-treatment CT scan/MRI in multidisciplinary discussion with surgeon and radiation oncologist (anticipated macroscopically complete resection, R0/R1 resection)
* Age: 18 years or older
* ECOG performance status ≤2
* Absence of history of bowel obstruction, mesenteric ischemia, or severe chronic inflammatory bowel disease.
* Normal renal function (calculated creatinine clearance ≥50 mL/min)
* Normal bone marrow and hepatic function (white blood cell count ≥2·5 × 10⁹ cells per L, platelet count ≥80 × 10⁹ cells per L, and total bilirubin \<2 times upper limit of normal)
* Women of child-bearing potential must have a negative pregnancy test within 3 weeks prior to the first day of study treatment
* Patients capable of childbearing/reproductive potential should use adequate contraception
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Sarcoma originating from bone structure, abdominal or gynecological viscera
* Any of the following histological subtypes: gastrointestinal stromal tumor, rhabdomyosarcoma, primitive neuroectodermal tumor or other small round blue cell sarcoma, osteosarcoma, chondrosarcoma, aggressive fibromatosis, or sarcomatoid or metastatic carcinoma
* Prior RT to the RPS
* Prior abdominal or pelvic irradiation for other prior malignancy or other disease
* Prior different invasive malignancy may be eligible per the discretion of the treating investigator and review by the Principal Investigator (PI)
* Prior chemotherapy or immunotherapy within 6 weeks of start of RT
* Pregnant women are excluded from this study because RT has the potential for teratogenic or abortifacient effects.
* HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for increased sensitivity to RT