Esophageal Cancer
Conditions
Keywords
Fluorescence, Endoscopy, Bevacizumab-800CW, Locally advanced esophageal cancer
Brief summary
For locally advanced esophageal cancer (EC), neoadjuvant chemoradiotherapy (nCRT) for 5 weeks followed by esophagectomy and lymphadenectomy, if necessary, is standard of care. It is reported that the pathological complete response (pCR) rate after nCRT ranges from 16% to 43%, with a median of 26.5%. According to current clinical guidelines, patients who achieved pCR still go for surgery even though those patients who achieved pCR may not benefit from surgery. Besides, about 50% of EC patients may have post-operative complications including pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, which lead to low health-related quality of life (HQoL). The golden standard to test the pathological response is by pathological assessment of the surgical specimen and thus after surgery. Theoretically, if pCR after nCRT can be predicted accurately before surgery by advanced imaging techniques, patients could have a wait-and-see. The wait-and-see procedure includes regular follow-up and salvage surgery if recurrence is present. Therefore, molecular fluorescence endoscopy (FME) using near-infrared fluorescence (NIRF) tracer bevacizumab-800CW targeting vascular endothelial growth factor combined with high-definition white light (HD-WL) endoscopy is expected to be a promising technique to monitor pCR and fill the gap.
Detailed description
See brief summary
Interventions
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to the endoscopic procedure
A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the standard clinical endoscope. Fluorescence imaging will be performed prior to and post the chemoradiotherapy.
Sponsors
University Medical Center Groningen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Locally advanced esophageal carcinoma (cT1b-4a N0-3 M0) in multi-disciplinary esophageal oncology meeting agreed on long course neoadjuvant chemoradiotherapy, followed by esophagectomy; * Age ≥ 18 years; * Written informed consent.
Exclusion criteria
* Patients with psychological diseases or medical issues who are not able to sign informed consent form; * Concurrent uncontrolled medical conditions; * 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 primary tumor prior to start of neoadjuvant chemoradiotherapy * Received a different investigational drug within 30 days prior to the dose of bevacizumab-800CW; * History of infusion reactions to bevacizumab or other monoclonal antibodies;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Discrimination of tumorous and non-tumorous tissue based on in vivo and ex vivo fluorescence measurements from bevacizumab-800CW gained during fluorescence endoscopy procedure | Three days after tracer injection | To determine the sensitivity of the marker bevacizumab-800CW in discriminating between tumorous and non-tumorous tissue prior to and post neoadjuvant chemoradiotherapy, to identify patients who benefit from the chemoradiotherapy. |
| Safety of bevacizumab-800CW administration by monitoring vital signs and/or (serious) adverse events. | Up to 14 days after tracer injection | Monitoring vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to the administration of bevacizumab-800CW |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To localization and distribution of bevacizumab-800CW fluorescent signal at cell level observed in vivo by confocal laser endomicroscopy (CLE) | Up to 1,5 year | CLE is a confocal laser endomicroscopy system which enables in vivo microscopic images of the tissue |
| The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results | Up to 1,5 year | Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities. |
| The variation in fluorescence intensity between fluorescence molecular endoscopy before and after neoadjuvant chemoradiotherapy defined as the tumor to background ratio and intrinsic fluorescence. | Up to 1,5 year | Both the images and specific measurements are used to calculate the fluorescence intensity (TBR & intrinsic fluorescence) and a difference between the before and after intensity is calculated. |
| Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy | Up to 1,5 year | Imaging of the distribution of bevacizumab-800CW with a fluorescence microscoop. |
| Quantification of the fluorescent signal by MDSFR/SFF spectroscopy | Up to 1,5 year | Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo. |
Countries
Netherlands
Outcome results
None listed