Evaluation of a Clinical Prototype Near-InfraRed Fluorescence (NIRF) Imaging Device for Lymph Node Mapping in Esophageal Cancer: a Technical Feasibility Study

Esophageal cancer is the 6th leading cause of cancer-related death in the
world, and its incidence is increasing dramatically in the western world. The
mainstay of curative treatment is esophagectomy. Current limitations in surgery
are inadequate lymphadenectomy (too few or no lymph nodes), inadequate primary
tumor resection (involved resection margins, circumferential resection margin
<= 1 mm, microscopic or macroscopic irradical resection) and undetected distant
metastases, all of which result in a poorer outcome for the patient. The
detection of lymph nodes, based on the propagation of cancer cells in the
lymphatic system, allows a better evaluation of tumor staging, prognosis and
therapeutic strategy determination.

This project intends to investigate a new medical instrument for mapping
draining lymph nodes and provide real-time feedback for the surgeon. An
intra-operative Near Infrared Fluorescence (NIRF) camera will be evaluated for
its technical feasibility to detect draining lymph nodes from esophageal
cancer. In course, this technique will be expanded upon by introducing folate
receptor fluorescein-isothiocyanate (FITC). The end-goal of this intraoperative
imaging instrument, designed by physicians and physicists, and its combination
with a folate-FITC optical contrast agent is to improve the detection of
involved lymph nodes, tumor delineation and distant metastases at the pleura or
peritoneum. By doing so, it may increase the efficiency and completeness of
resection, ultimately resulting in a better outcome for the patient. Clinical
oncologist surgeons and fundamental physics applied to medical imaging
researchers are involved in this project.

Primary:
Evaluate the ergonomics and function of the imaging system - the NIRF imaging
system should not interfere with the standard esophagus resection and
lymphadenectomy procedure by the surgeon while detection of indocyanine green
(ICG) takes place for lymph node mapping. Duration: ~30 minutes real-time .

Secondary:
To test if an intraoperative NIRF camera system can detect a NIRF optical
contrast agent for lymph nodes, and their numbers, in patients with operable
esophageal cancer.

Interventional phase 0 technical feasibility study / non-randomized, open
label, uncontrolled, single group assignment.

Patients with operable esophageal cancer undergoing esophagectomy with
two-field-lymphadenectomy, either by a left- or right-sided
abdomino-thoracotomy, will receive pre-operatively an intratumoral injection
with indocyanine green (ICG) during endoscopy guided by ultrasound (EUS).
During the operative procedure NIRF imaging for detection of draining lymph
nodes (i.e. ICG accumulation) will take place.

The burden associated with participation consists of an injection of
indocyanine green (ICG) intratumoral intra-operatively for the detection of the
draining lymph nodes. Additionally, there is a chance of longer operative
procedure by using a NIRF imaging camera (~30 minutes).
1. The possible most serious adverse event for injection of ICG is an allergic
and anaphylactic reaction, as described in the SPC.
2. The possible effect of prolonged anesthesia because of testing the camera
system and detection of the lymph nodes is limited in itself because lymph node
mapping is executed during the actual surgery. Nevertheless, we will limit
imaging time, and possible prolongation of the procedure to a maximum of 60
minutes.
3. There is no risk or burden of using the intraoperative imaging device, all
necessary test for use of electrical devices in the OR are covered.
4. There is no risk of infection; the imaging device will be covered by special
designed sterile drapes to prevent the risk of infection during a surgical
procedure.