To investigate the feasibility of evaluation of prevalence and clinical significance and relevance of circulating tumor cells (CTC) in the blood of patients with resectable adenocarcinoma of the esophagus (EAC) treated with multimodal therapy in a pilot study. The primary hypothesis is that the number of CTC correlates with tumor burden and response to treatment. One established and one experimental CTC detection platform will be investigated. Investigators will evaluate the prevalence and enumeration of CTC before neoadjuvant treatment (time point 1), after neoadjuvant treatment & before operation (time point 2) and after the operation (time point 3). Results will be compared with healthy controls (one time point) and correlated with conventional response to treatment evaluation. The persistent presence of CTC could be a marker for worse response to treatment and predict early recurrence.

Little is known of the prevalence and clinical relevance of CTC in EAC, with the available data arising from heterogeneous patient populations using varied detection methods; but they are promising tools to improve staging and prediction of treatment response to perioperative and operative therapy.

The limited reports on resectable EAC use the epithelial-antibody dependent CellSearch method for CTC isolation and report a CTC-positivity rate of only 15-18% in non-pre-treated patients but with clinical relevance. It is thus needed to evaluate the relevance of CTC in the context of multimodal treatment courses.

This pilot study will investigate the CTC in the blood of patients with resectable EAC treated with multimodal therapy. Data on prevalence and enumeration of CTC will be generated. Two CTC isolation methods will be investigated, the established and expensive surface-antibody-dependent CellSearch method, and the antibody-independent and less expensive isolation by size (ISET; ScreenCell) method. The ISET method will additionally be investigated in healthy controls to get data on specificity.

The study can accomplish several goals through the use of two CTC detection platforms: 1) to determine the prevalence and number of CTC in resectable EAC under multimodal treatment, and 2) to investigate the potential role of CTC in predicting response to treatment and prognosis before neoadjuvant treatment, after neoadjuvant treatment and before operation as well as after the operation.

The primary hypothesis is that the enumeration of the CTC correlates with tumor burden and will reflect the response to treatment. To date the response to treatment is assessed with a combination of CT-morphologic, endoscopic, clinical (dysphagia) and finally histology. This assessment is used as control.

Inclusion Criteria:

• Histologically verified adenocarcinoma of the esophagus According to the UICC definition (TNM7),
• pre-treatment stage cT1N+, M0 or cT2-4aN0/N+, M0 ,
• Age≥18 years,
• scheduled for a multimodal therapeutic concept.

Exclusion Criteria:

• Tumors of squamous, adenosquamous or other non-adenocarcinoma histology, patients with advanced inoperable or metastatic esophageal adenocarcinoma.
• Esophageal adenocarcinoma cT1N0 and cT4b,
• Gastric carcinoma.
• Prior chemotherapy for gastrointestinal cancer. Clinically not eligible for surgery