Radiation and chemotherapy can shrink the tumor. For certain types of cancer, immunotherapy is added to further reduce the tumor size. Immunotherapy works for some patients and can sometimes keep the cancer under control for a long time. Unfortunately, immunotherapy does not work for every patient. That's why researchers around the world are looking for new ways to predict who will benefit from immunotherapy and who will not.

It is likely that immunotherapy is more effective when the tumor or immune cells have specific targets, such as the proteins PD-L1 or PD-1. Unfortunately, clinicians cannot reliably detect these proteins through blood tests or tissue samples, because their presence can vary throughout the tumor.

With this study, the investigators hope to use a new technique called 'fluorescence endoscopy' during an endoscopic ultrasound of the esophagus to visualize whether the PD-L1 or PD-1 proteins are present in esophageal cancer or immune cells. Additionally, the investigators aim to investigate whether the presence of these proteins changes before and after chemotherapy and/or radiation. This will help us determine the best timing for measuring these proteins in the future.

What is fluorescence endoscopy? To determine whether the proteins are present, participants in this study will receive two 'tracers' via an IV beforehand. The first tracer is a fluorescent substance-a kind of 'glow-in-the-dark' compound-attached to a drug that binds to PD-L1 proteins in esophageal cancer. The second fluorescent tracer binds to PD-1 proteins on immune cells.

During fluorescence endoscopy, the investigators use special equipment to detect these tracers in the esophagus. This information may help us better identify which patients are suitable for immunotherapy treatment and which are not.

Inclusion Criteria:

• Lesion suspected for locally advanced EC (cT1b-4a N0-3 M0);
• Indication for neoadjuvant therapy or definitive chemo-radiation 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 and on active treatment;
• 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 tracer administration according to the patient's medical history;
• History of infusion reactions to durvalumab or nivolumab or other monoclonal antibodies according to the patient's medical history;