The goal of this trial is to learn if adding consolidative chemotherapy to routine chemoradiation can better control both local recurrence and metastasis and reduce the need for surgical intervention.

Inclusion Criteria:

• Subject must be able to provide study specific informed consent prior to study entry
• Must be newly diagnosed, histologically proven diagnosis of adenocarcinoma of the thoracic esophagus or gastroesophageal junction (Siewert I-II);
• Stage II-IVA, excluding T4b, according to the American Joint Committee on Cancer (AJCC) 8th edition;
• Complete history and physical examination within 21 days of signing consent;
• Staging whole-body FDG-PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography) scan with or without contrast (preferred) or chest/abdominal (CT with contrast) confirming there is no evidence of metastatic disease must be obtained within 45 days of study enrollment
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-2
• Subjects must be appropriate candidates for planned chemoradiation (concurrent carboplatin/paclitaxel) and chemotherapy (FLOT, m-FOLFOX-6) as determined by the treating radiation oncologist, medical oncologist, and surgical oncologist.
• Adequate hematologic, renal, and hepatic function within 14 days of initiation of therapy

Exclusion Criteria:

• Cervical esophageal cancers arising 15-18 cm from the incisors.

• Esophageal squamous cell carcinoma.

• Patients with T4b disease according to the AJCC 8th Edition.

• Definitive clinical or radiologic evidence of metastatic disease.

• Has had prior systemic therapy or radiation therapy for the current diagnosis.

• Prior thoracic radiotherapy for any reason that would result in overlap of radiation therapy fields; all patients with prior radiotherapy must be reviewed by the PI to determine if patient is eligible.

• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

• Severe, active co-morbidity defined as follows:

  • Active uncontrolled infection requiring IV antibiotics;
  • Pregnant and/or nursing subjects;
  • HIV positive with CD4 count < 200 cells/microliter. Note that subjects who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive.

• Has a history or current evidence of physical or physiological contraindication to participation in this study, at the discretion of the treating investigator.

• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Data may be shared 6 months after publication or as required by the journal