RATIONALE: PET scans done during chemotherapy may help doctors assess a patient's response to treatment and help plan the best treatment.

PURPOSE: This randomized phase II trial is studying 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.

• Surgically resectable, histologically confirmed esophageal adenocarcinoma, including Siewert gastroesophageal (GE) junction adenocarcinomas types 1 and 2
• T1N1-3M0 or T2-4NanyM0 as determined by endoscopic ultrasound (EUS) and PET/CT (histologic confirmation of lymph involvement is not required); all disease (tumor and nodes) must be both surgically resectable and capable of containment in a radiotherapy field; no T4 tumor with clear evidence of invasion of the vertebral column, heart, great vessels, or tracheobronchial tree
• All patients must have locoregional staging determined by endoscopic ultrasound (EUS) if technically feasible; endoscopy reports or subsequent gastrointestinal (GI) clinic note should clearly state both the T and N stage
• No evidence of distant metastases (as determined by EUS or PET/CT)
• Patients with cervical, supraclavicular, or other nodal disease that is either not included in the radiation field or is not able to be resected at the time of esophagectomy are not eligible
• Patient must have pre-resection tissue available for central pathology review, in case that the patient has a pCR at the time of surgical resection to confirm diagnosis
• Patients must have an fludeoxyglucose F 18 (FDG)-avid tumor with a maximum standard uptake value (SUVmax) of >= 5.0 on baseline PET/CT scan of primary tumor; baseline PET/CT scan should be performed; if it is necessary to repeat baseline PET/CT scan, reimbursement information is available
• No prior malignancy within 5 years of registration, with the exception of basal or squamous cell skin cancers, or in situ bladder or cervical cancer; patients with prior malignancy treated with surgery only and disease free for more than 5 years are eligible; however, no prior thoracic radiation therapy (RT) or abdominal RT or chemotherapy allowed
• No known contraindication to the use of fluorouracil, taxanes, or platinum compounds
• No history of severe hypersensitivity reaction to Cremophor EL
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patient must be non-pregnant and non-nursing; women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to randomization; women of child-bearing potential include any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35mIU/mL); even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
• Absolute neutrophil count (ANC) >= 1,500/μL
• Platelet count >= 100,000/μL
• Bilirubin =< 1.5 times upper limit of normal (ULN)
• Calculated creatinine clearance >= 60 mL/min
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 times ULN