Dose Escalation of Neoadjuvant Proton Beam Radiotherapy With Concurrent Chemotherapy in Locally Advanced Esophageal Cancer

• To identify the maximally tolerated radiation dose (MTD) of dose-escalated proton radiotherapy in combination with carboplatin/paclitaxel in the preoperative setting for esophageal cancer.
• To estimate pathologic response rates by esophagectomy surgical specimens after escalated doses of chemoradiotherapy.
• To assess the utility of circulating tumor cells and tumor vesicles as biomarkers to predict treatment response to chemoradiotherapy

Inclusion criteria

• Patients with a histologic diagnosis of adenocarcinoma of the esophagus located distal to the carina
• Patients with AJCC 7th edition clinical stage IIB-IIIC
• Patient must be >18 years of age.
• Patients must have an ECOG Performance Status of 0-1
• Patients must be able to provide informed consent.
• Patients must be surgical candidates with adequate hematologic, renal, hepatic and pulmonary function
• serum AST and ALT < 2 times the upper limit of normal
• Patients must have bilirubin < 1.5 × normal.
• WBC > 3000/mm3, platelets > 100,000 mm3.
• Hemoglobin > 10 g/dL serum creatinine < 1.5 times the upper limit of normal
• Women of child-bearing potential as long as she agrees to use a recognized method of birth control (e.g. oral contraceptive, IUD, condoms or other barrier methods etc.). Hysterectomy or menopause must be clinically documented.

Exclusion criteria

• Patients with primary tumors exceeding 8 cm in length or 5 cm in width ( length should be measured by endoscopic findings, width should be measured by diagnostic CT or CT portion of PET/CT)
• Patients with primary tumors located at or above the carina
• Prior or simultaneous malignancies within the past two years (other than cutaneous squamous or basal cell carcinoma, melanoma in situ or thyroid carcinoma)
• Pregnant women, women planning to become pregnant and women that are nursing