This phase I trial studies the side effects and best dose of stereotactic body radiation therapy in treating patients with ovarian or uterine cancer that has come back. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue.

This is a phase I study with a primary objective to determine maximum tolerated dose (MTD) of 3 fraction stereotactic body radiation therapy (SBRT) for abdominopelvic recurrences of ovarian cancer (OC) and uterine papillary serous carcinoma (UPSC). This is a dose escalation study that employs a 3+3 design to determine the MTD. Patients are then monitored closely to determine side effects and adverse events, as well as success rates and tumor response to the radiation therapy.

Inclusion Criteria:

• Female patients > 18 years of age.
• ECOG 0 or 1.
• Diagnosis of primary ovarian cancer of any histology (patients with diagnoses of fallopian tube and primary peritoneal cancer are also eligible), or primary uterine cancer of papillary serous histology.
• Pathologic confirmation of eligible histology.
• Three or fewer total sites of active disease (at least one site of active disease to be treated on study must be confined to the abdomen or pelvis excluding liver and must be < 5 cm in greatest dimension as determined by pre-screening cross-sectional imaging).
• Additional site(s) of active disease (such as parenchymal liver and lung metastases, or supraclavicular nodal metastases), should be considered for treatment (off study) with radiation, surgery, or another form of local therapy, at the discretion of the study PI.
• Systemic therapy is allowed but SBRT cannot begin until > or = 7 days after the last cycle of systemic therapy, and systemic therapy cannot be initiated or re-initiated until > or = 7 days after SBRT. There will be no limit on prior lines of systemic therapy.
• Patients with contraindications to intravenous (IV) contrast administration are still eligible for this study if the tumor can be delineated clearly without IV contrast (at the discretion of the treating radiation oncologist) but will not participate in the functional imaging studies.

Exclusion Criteria:

• Pregnant women. If patients are not status post bilateral salpingo-oopherectomy then pregnancy testing is required.
• Patients with active collagen vascular disease (CVD), specifically systemic lupus erythematosus or scleroderma. Patients with a history of CVD without evidence of active disease are eligible for enrollment at the discretion of the study PI.
• Patients with inflammatory bowel disease and/or GI ulcers and/or GI fistulas are eligible but only at the discretion of the study PI after personalized review of their medical history and proximity of SBRT targets to gastrointestinal mucosa.
• Patients with a separate non-cutaneous cancer diagnosis for which the patient has not been without evidence of disease for at least 5 years.