Inclusion Criteria:  Ability to understand a written informed consent document, and the willingness to sign and date it. Stated willingness to comply with all study procedures and be available for the duration of the study. Male or female between the ages of 18 and 80 years. Newly diagnosed, cT3-T4 or node-positive adenocarcinoma of esophagus or gastroesophageal junction as assessed by PET/CT or CT of the chest, abdomen and pelvis and/or by endoscopic ultrasound, with pathologic diagnosis obtained within one month of signing consent, without delivery of prior chemotherapy or radiation therapy. Subjects must be previously untreated with systemic chemotherapy or radiation therapy. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. Adequate bone marrow function: white blood cell (WBC) count > 3 x 10^9/L; hemoglobin > 8 g/dL; platelets > 100 x 10^9/L. Adequate liver function: total bilirubin < 1.5 x upper limit of normal; aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN); alanine aminotransferase (ALT) < 3 x upper limit of normal); serum creatinine < 1.5 x ULN. Women and men of childbearing age should use contraceptives throughout the treatment period of the study. Ability to obtain tissue sample for ctDNA analysis and detectable baseline ctDNA level. Concurrent participation in other clinical studies that will not affect the general sequence of therapies in the trial schema of this study would be allowed. Adjuvant chemotherapy or immunotherapy would be allowed as this is an observational study and would be at clinician's discretion.  Exclusion Criteria:  Subjects with metastatic gastric or gastroesophageal junction adenocarcinoma. Subjects with esophageal or gastroesophageal junction squamous cell carcinoma or adeno-squamous carcinoma. Prior treatment with chemotherapy or radiation therapy for gastric or gastroesophageal adenocarcinoma. Subjects that received treatment for a second primary malignancy within one year of screening will be excluded, however pts. with h/o early-stage cancers treated with curative intent, including basal or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast would be eligible. Subjects with greater than grade 2 peripheral neuropathy. Any serious or uncontrolled medical disorder or active infection, which in the opinion of the investigator may increase the risk associated with study participation, study treatment administration, or would impair the ability of the subject to receive study treatment. Known history of active hepatitis B or hepatitis C. Clinically unstable cardiac disease, including unstable angina, congestive heart failure, ventricular arrhythmia. History of allergy or hypersensitivity to any of the study drugs or study drug components. Contraindications to any of the study drugs of the chemotherapy regimens selected by the investigator. Known history of dihydropyridine dehydrogenase (DPD) deficiency. Female patients who are pregnant, nursing or lactating.