To determine the safety of moderately hypofractionated radiation in the treatment of primary and locally recurrent RPS, based on the evaluation of acute radiation-related toxicity profile of each participant (30-day radiation toxicity)

To determine the safety of moderately hypofractionated radiation in the treatment of primary and locally recurrent RPS, based on the evaluation of acute radiation-related toxicity profile of each participant (30-day radiation toxicity)

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