Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers

Inclusion Criteria:

1. Patients must have a histologically, cytologically, or radiographically confirmedmetastatic gastrointestinal (GI) malignancy (esophageal, gastroesophageal, gastric,small intestine, hepatocellular, pancreaticobiliary, colorectal, or anal cancer).

2. Patients must be receiving immunotherapy (checkpoint inhibitor or CTLA4 inhibitor)with overall response of progressive disease by RECIST criteria.

3. Patients must have at least two metastases which are individually progressing as perRECIST criteria, one of which can be safely unirradiated as adjudicated by thetreating radiation oncologist (e.g. lesions for which small increases in dimensionsare unlikely to precipitate significant symptoms).

4. Patients must have 1-5 sites of disease meeting standard-of-care indications forpalliative radiation therapy as adjudicated by the treating radiation oncologist.For example:

• Symptomatic disease causing pain, bleeding, dyspnea, dysphagia, or nausea

• At-risk for neurologic, respiratory, cardiovascular, gastrointestinal,musculoskeletal, or hepatobiliary compromise

5. Evaluation by a radiation oncologist within 28 days of study registration.

6. Must have adequate organ function to administer radiation therapy and immunotherapyas per standard of care.

7. Age >= 18 years.

8. Life expectancy exceeding 6 months.

9. Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky performance status >= 50.

10. Radiation therapy is known to be teratogenic and therefore women of child-bearingpotential and men must agree to use adequate contraception (hormonal or barriermethod of birth control) prior to study entry and for the duration of radiationtherapy. Should a woman become pregnant or suspect she is pregnant while she or herpartner is participating in this study, she should inform her treating physicianimmediately. Men treated or enrolled on this protocol must also agree to useadequate contraception prior to the study and for 3 months after completion ofradiation therapy. Contraception requirements during the follow-up period of 6months will be according to standard of care for immunotherapy administration. a. If a woman is of child-bearing potential, a negative pregnancy test within 28days prior to study enrollment is required.

11. Ability to understand a written informed consent document, and the willingness tosign it.

Exclusion Criteria:

1. Enrollment on immunotherapy clinical trial for which radiation therapy is notpermitted.

2. Administration of radiation therapy within 4 weeks prior to study enrollment.

3. Treatment with systemic corticosteroids or other immunosuppressive medications whichwould significantly diminish the effect of immunotherapy as judged by the treatingphysician.

4. Radiation therapy is contraindicated as adjudicated by the radiation oncologist.