Accelerated Hypofractionated Intensity Modulated Radiation Therapy and Combination Chemotherapy for the Treatment of Unresectable Esophageal or Gastroesophageal Junction Cancer

Inclusion Criteria

• Biopsy-proven carcinoma of the thoracic esophagus, or gastroesophageal junction (GEJ)
• Amenable to definitive chemoradiation
• Unresectable esophageal cancer or not a surgical candidate as determined by a surgeon or multidisciplinary tumor board
• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 60 days prior to registration with adequate bone marrow function)
• Platelets >= 100,000 cells/ mm^3 (obtained within 60 days prior to registration with adequate bone marrow function)
• Hemoglobin >= 9 g/dL (transfusion or other intervention to achieve hemoglobin >= 9 g/dL is acceptable) (obtained within 60 days prior to registration with adequate bone marrow function)
• Serum creatinine =< 1.5 x upper limit of normal or calculated creatinine clearance >= 50 mL/min within 60 days prior to registration estimated by the Cockcroft-Gault formula
• Bilirubin =< 1.5 x upper limit of normal (within 60 days prior to registration)
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) (within 60 days prior to registration)
• Negative pregnancy test within 14 days of registration or otherwise be determined to not be of childbearing potential. Postmenopausal women must be amenorrheic for 12 months or more. Women of childbearing potential must agree to perform appropriate contraception methods and not breastfeed until 30 days after last chemotherapy
• Planned to undergo IMRT with photon beam radiation therapy. 3-dimensional conformal radiation therapy (3D CRT) and proton modalities are not allowed
• Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

• Primary cervical esophageal cancer
• Siewert-Stein type III carcinomas of the stomach
• Esophageal perforation, fistula, or deep ulceration to the mediastinum
• Currently receiving any other investigational agents
• Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel or other agents used in the study
• Planning to undergo or has already undergone induction chemotherapy
• Presence of any active malignancy within 2 years that may alter the course of esophageal cancer therapy
• Prior radiation therapy to the neck, thorax, or abdomen is not allowed UNLESS there is expected to be no overlap with the study esophageal radiotherapy treatment. Prior radiation therapy treatment plan reports must be reviewed by study principal investigator (PI) to verify no overlap of treatment fields
• Severe active comorbidity as defined below: * Unstable angina and/or congestive heart failure within the last 6 months * Transmural myocardial infarction within the last 6 months * History of stroke, cerebral vascular accident, or transient ischemic attack within the last 6 months * Serious and inadequately controlled cardiac arrhythmia * Bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration * Peripheral neuropathy > grade 1 at time of registration
• Persistent complications from any major surgery within 4 weeks of study treatment start
• Any other major medical illness that in the investigator’s opinion would prevent safe administration or completion of protocol therapy
• Pregnant or lactating woman. Women of childbearing potential with positive pregnancy test at baseline, or women who have not taken a pregnancy test at baseline. A man or woman who does not agree to use appropriate contraception
• Patients with human immunodeficiency virus (HIV) are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective antiretroviral therapy (ART) according to United States Department of Health and Human Services (DHHS) treatment guidelines is recommended