Treatment of patients with locally advanced esophageal cancer (EC) is multidisciplinary and consists of neoadjuvant therapy followed by surgical removal of the esophageal tumor and potentially tumor positive lymph nodes. The beneficial effect of the addition of immunotherapy to improve response rates to current treatment strategies has been investigated response to, since only 16 to 43% of EC patients achieve a pathological complete response (pCR) after neoadjuvant therapy and a pCR is associated with better long-term outcomes. Unfortunately, not all patients respond to immunotherapy and the knowledge about biomarkers that predict response to therapy are required. A promising novel parameter is tumor programmed death-ligand 1 (PD-L1) expression, one of the immune checkpoints targeted by cancer immunotherapy. Studies performed in patients with various solid tumors demonstrate improved response to immunotherapy and survival benefit in patients with higher PD-L1 expression. Nonetheless, not all patients with high PD-L1 expression show benefit and some without expression do. Moreover, mostly biopsy-based tests are used to assess PD-L1 status, although these tests are prone to errors, partly due to heterogeneity in tissue expression. Novel methods are needed to gain more insight in the PD-L1 expression in order to better select patients who are likely to benefit from immunotherapy. The investigators hypothesize that quantitative fluorescence endoscopy using the tracer durvalumab-680LT targeting PD-L1 is a promising technique to investigate the heterogeneity of PD-L1 expression.

Inclusion Criteria:

• Lesion suspected for locally advanced EC (cT1b-4a N0-3 M0)
• Indication for neoadjuvant therapy
• Age ≥ 18 years;
• Written informed consent.

Exclusion Criteria:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent according to treating medical physician;
• Concurrent uncontrolled medical conditions according to treating medical physician;
• Medical history of auto-immune disease
• Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause);
• Irradical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of the primary tumor prior to start of neoadjuvant therapy according to the patient's medical history;
• Received an investigational drug within 30 days prior to the dose of durvalumab-680LT according to the patient's medical history;
• History of infusion reactions to durvalumab or other monoclonal antibodies according to the patient's medical history;