PET Scan Imaging in Assessing Response in Patients With Esophageal Cancer Receiving Combination Chemotherapy

OBJECTIVES: Primary * To induce a complete pathologic response (pCR) rate of 20% in positron emission tomography (PET) scan non-responders treated with either induction FOLFOX or carboplatin/paclitaxel, who then crossover to the other regimen during radiotherapy. Secondary * To compare PET/CT response between induction treatment arms. * To compare pCR between induction treatment arms among PET/CT scan responders. * To directly compare pCR between induction treatment arms among non-responders if both treatment regimens are found to be efficacious. * To determine 8-month progression-free survival (PFS) in PET/CT scan responders, and in non-responders treated with alternative crossover chemoradiotherapy. * Estimate the PFS and overall survival (OS) curves, overall and among PET responders and PET/CT non-responders by induction treatment. * To determine the rate of postoperative anastomotic leak after neoadjuvant chemotherapy followed by chemoradiation. * To evaluate immunohistochemistry and RT-PCR of ERCC1, and genetic polymorphisms of ERCC1, XPD, and XRCC1. * To evaluate status and levels of methylation of nine candidate biomarker genes as well as expression levels of selected specific microRNAs, which will be correlated with chemoradiation response. * To compare the quality of life (QOL) of responders and nonresponders (as determined by PET/CT scanning) to presurgical treatment for esophageal cancer, in terms of global QOL, physical symptoms, physical functioning, and emotional well-being. * To examine the association between OS and QOL in esophageal cancer patients treated with chemotherapy, chemoradiation therapy, and surgery. OUTLINE: This is a multicenter study. Patients are stratified according to T-stage (T1-2 vs T3-4) and nodal status (N0 vs N+). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive modified FOLFOX-6 therapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously on days 1-5. Treatment repeats every 14 days for 3 courses. Patients then undergo PET/CT scan. Patients with responsive disease (tumor metabolic activity decreased by ≥ 35%) receive 3 additional courses of FOLFOX-6 therapy and undergo concurrent radiotherapy (RT) (3D-conformal or intensity-modulated) once daily, 5 days a week, for approximately 6 weeks. Patients without responsive disease (tumor metabolic activity did not decrease by 35%) cross over to arm II during RT. * Arm II: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 2 courses. Patients then undergo PET/CT scan. Patients with responsive disease (tumor metabolic activity decreases ≥ 35%) continue to receive carboplatin IV over 30 minutes and paclitaxel IV over 1 hour once weekly for 5 weeks and undergo RT (3D-conformal or intensity-modulated) once a day, 5 days a week, for approximately 6 weeks. Patients without responsive disease (metabolic activity did not decrease by 35%) cross over to arm I during RT. Within 4-10 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgery at the discretion of the treating team. Patients may undergo blood sample collection at baseline and periodically during study for correlative studies. Patients may also complete quality-of-life questionnaires at baseline and periodically during study. After completion of study therapy, patients are followed up periodically for 5 years.