Metabolomic and BH3 Profiling of Esophageal Cancers: Identification of Novel Assessment Methods of Treatment Response for Precision Therapy

Study Summary

Background: The number of patients with esophageal cancer keeps rising. For many patients, a combination of surgery, chemotherapy, and radiation is necessary to completely treat the disease. Usually, patients receive chemotherapy and radiation at the same time followed by surgery to remove the part of the esophagus with the tumor (Neoadjuvant chemoradiotherapy (nCRT)). Researchers want to learn how to make this treatment more effective. Objective: To see if biopsies before treatment can show which patients will do the best with a combination of chemotherapy, radiation, and surgery. Eligibility: Adults at least 18 years old with esophageal adenocarcinoma or squamous cell carcinoma who should be treated with chemotherapy, radiation, and surgery. Design: Patients will undergo standard testing that is routine for all patients with this disease. These tests include: Medical history Physical exam with activity and nutritional assessment Standard lab tests Imaging studies including a computerized axial tomography (CAT) scan and positron-emission tomography (PET) scan Breathing test into a machine to measure size and function of lungs. Biopsy for a small sample of tumor is removed by esophagogastroduodenoscopy (EGD): A tube inserted into the mouth under anesthesia Endoscopic ultrasound is performed in some but not all patients. Patients will have nCRT at the clinic or with their local doctor. In 6 -12 weeks after nCRT, patients will undergo surgery with: 1. A robotically-assisted, minimally-invasive esophagectomy 2. Or, a traditional, open approach. After surgery, patients are usually in the hospital for 2 weeks and have a feeding tube for at least 2 weeks and potentially longer until they are eating enough to not lose weight. Patients will return for follow-up visits with labs and CAT scans every 6 months for the first two years then every year afterwards.

Primary Outcome

Specimens of normal esophagus, esophageal tumors, blood, or urine will be analyzed to determine specific signatures and outcome of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal adenocarcinoma or squamous cell carcinoma. Response will be defined by the Mandard Score. Major response with no viable tumor (Grade 1) and \<10% viable tumor (Grade 2) versus non major response of \>10% viable tumor (Grade 3-5) as assessed by final pathology. Grade 1-2 is

Interventions

• PROCEDURE Esophagectomy
• OTHER Chemoradiotherapy