Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body

Inclusion Criteria:

• REGISTRATION TO STEP 1

• Patient must have histologically confirmed HER2 negative metastatic esophageal orgastric adenocarcinoma (American Joint Committee on Cancer [AJCC] 8th edition)

• Patient must have oligometastatic disease at the time of registration, which isdefined as the following:

• At most 3 radiologically visible metastatic lesions (not sites), in addition tothe primary site. Computed tomography (CT) or magnetic resonance imaging (MRI)scans will be performed for staging purposes. Patients with oligometastaticsites that are only detected with positron emission tomography (PET)/CT will beeligible for participation, as long as radiation planning and administration isfeasible after discussion with treating radiation oncologist. Malignant lymphnode should be at least 1 cm in size or biopsy proven involved by disease

• Anatomically defined lymphadenopathy will be considered as 1 site of metastaticdisease. For example, 2 enlarged paraaortic lymph nodes will be considered asone site, and 2 additional sites will be allowed to meet protocol definition ofoligometastatic disease. However, if supraclavicular or cervical nodes areinvolved for distal esophageal tumors or gastric tumors, these are countedseparately from intrathoracic nodes. For upper thoracic/cervical esophagealtumors, the involvement of celiac nodes are counted separately fromintrathoracic nodes. Intrathoracic nodes, defined as hilar and mediastinalnodes, will be collectively counted as one

• Patients with radiologically evident peritoneal metastasis will be excluded.

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Women of childbearing potential and sexually active males must not expect toconceive or father children by using accepted and effective method(s) ofcontraception (both double barrier contraception and birth control pills orimplants) or by abstaining from sexual intercourse for at least one month after thelast dose of protocol treatment and continuing for 5 months after the last dose ofprotocol treatment (for female patients) and for 7 months after the last dose ofprotocol treatment (for male patients who are sexually active with women of childbearing potential [WOCBP]). Investigators must counsel WOCBP and male patients whoare sexually active with WOCBP on the importance of pregnancy prevention and theimplications of an unexpected pregnancy

• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained within 28 days prior toregistration)

• Hemoglobin >= 8 g/dL (obtained within 28 days prior to registration)

• Platelets (PLT) >= 100 x 10^9/L (obtained within 28 days prior to registration)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limitof normal (ULN) (obtained within 28 days prior to registration)

• Bilirubin =< 1.5 x institutional ULN (obtained within 28 days prior to registration)

• Serum creatinine =< 1.5 x institutional ULN (Cockcroft and Gault formula) (obtainedwithin 28 days prior to registration)

• Albumin > 2.5 g/dL (obtained within 28 days prior to registration)

• Patient must be able to understand and willing to sign and date the writtenvoluntary informed consent form prior to any protocol-specific procedures

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months are eligible for this trial.Patients must have CD4 > 200 at the time of registration

• NOTE: HIV testing is not required for eligibility

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

• Patients who had prior definitive treatment for early stage EGA with either surgeryor chemoradiation are eligible for participation as long as recurrent diseasedeveloped at least 6 months after completion of all prior therapies

• Any major surgery must have been completed >= 4 weeks prior to registration

• REGISTRATION TO STEP 2

• Patient must have histologically confirmed HER2 negative metastatic esophageal orgastric adenocarcinoma (AJCC 8th edition) with stable disease after about 4 monthsof fluorouracil, leucovorin calcium, and oxaliplatin (FOLFOX) or 6 cycles ofcapecitabine and oxaliplatin (CAPOX) (Step 1 treatment)

• Patient must have no evidence of disease progression based on Response EvaluationCriteria in Solid Tumors (RECIST) criteria since Step 1 registration. Patients withcomplete radiologic response are eligible for Step 2

• Patient must have an ECOG performance status 0-1

Exclusion Criteria:

• Patient must not have any contraindications to 5-fluorouracil (5-FU) orcapecitabine, oxaliplatin

• Patient must not have any contraindications to radiation therapy based onconsultation with a radiation oncologist. Formal radiation oncology evaluation willbe required for eligibility purposes. Prior palliative or definitive radiation tothe primary site is allowed, as long as it was completed at least 2 weeks beforeregistration

• Women must not be pregnant or breast-feeding due to the potential harm to unbornfetus and possible risk for adverse events in nursing infants with the treatmentregimens being used

• All females of child bearing potential must have a serum or urine pregnancytest to rule out pregnancy within 14 days prior to registration

• A female of childbearing potential is any woman, regardless of sexualorientation or whether they have undergone tubal ligation, who meets thefollowing criteria: has achieved menarche at some point, has not undergone ahysterectomy or bilateral oophorectomy; or has not been naturallypostmenopausal (amenorrhea following cancer therapy does not rule outchildbearing potential) for at least 24 consecutive months (i.e., has hadmenses at any time in the preceding 24 consecutive months)

• Patient must not have had any prior treatment with 5-FU or capecitabine and/oroxaliplatin containing systemic therapy

• NOTE: Patients previously treated with radiosensitizing doses of 5-FU will beeligible for participation as long as adequate time has elapsed from pasttreatments

• NOTE: Patients who received systemic 5-FU or capecitabine and/or oxaliplatin aspart of the treatment for their locoregional disease are eligible forparticipation, as long as all definitive therapy has been completed at least 6months prior to trial enrollment

• Patients with known central nervous system (CNS) metastasis will be excluded fromtrial participation, regardless of the status of the CNS disease

• Patient must not have any uncontrolled intercurrent illness including, but notlimited to ongoing or active infection requiring treatment, symptomatic congestiveheart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatricillness/social situations that would limit compliance with study requirements

• Patient must not have had live vaccines within 30 days prior to registration.Examples of live vaccines include, but are not limited to, the following: measles,mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette Guerin (BCG),and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generallykilled virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,Flu-Mist) are live attenuated vaccines and are not allowed