Multicenter study evaluating the hybrid approach using a novel fluorescence camera - Identifying the value of intraoperative fluorescence imaging during sentinel node biopsy procedures

The sentinel node biopsy procedure is conventionally performed via a
radioguided surgery approach. Upon the injection of a radiolabeled colloid
preoperative imaging is performed to determine the number and location of the
sentinel nodes. Intraoperatively then a gamma-ray detection probe is used to
guide the surgeon to the radioactive nodes. However, this approach does not
always allow optical sentinel node identification. Therefor, prior to the start
of the operation often a blue dye is injected. But, we have experienced that
blue dye does not always stain the node(s) blue. Therefore, in 2001, as a blue
dye alternative, the near-infrared fluorescence dye indocyanine green (ICG) was
introduced.
Recently we showed that using the hybrid tracer ICG-99mTc-nanocolloid, dthe
advantages of the conventional radioguided procedure could be combined with the
advantages of near-infrared fluorescence imaging. In feasibility studies we
found that using this hybrid approach, preoperative imaging findings could be
directly translated in to the operation room. Moreover, it was found that the
hybrid tracer significantly outperformed blue dye in terms of optical sentinel
node identification. However, for effective fluorescence imaging, lights in the
operation theatre have to be dimmed. This has resulted in fluorescence imaging
being used a confirmatory imaging modality. In a recent pilot study we then
evaluated a fluorescence camera that works under ambient light conditions.
Nevertheless, the value of this approach during the operation (for the patient
and the operating surgeon) remains to be investigated.

Primary objectives:
- Determine the value of fluorescence imaging-guided surgery under ambient
light conditions for the identification of hybrid tracer-containing SNs as seen
on preoperative imaging.

Secondary objectives:
- Determine the value (accuracy) of fluorescence imaging-assisted SN
identification to the conventional radioguided approach;
- Determine the value of fluorescence imaging-assisted SN identification to the
conventional blue dye-based approach;
- Evaluation of (post-operative) complications within 90 days after surgery
(Clavien-Dindo score);
- Evaluation of follow-up (local recurrence after SN biopsy).

A total of 670 patients will have to be included, of which 125 will be included
from the Netherlands. The number and location of the sentinel node(s) will be
determined following the hybrid tracer injection and preoperative imaging
(current routine). Intraoperatively, firstly fluorescence guidance will be used
to identify the sentinel node(s). If this is not successful within 15 min, the
conventional approach of radio- and fluorescence and blue dye guidance will be
used to identify the sentinel node(s).

On the morning of surgery, ICG-99mTc-nanocolloid will be injected peri- or
intratumorally Lymphoscintigrams and SPECT/CT imaging will be performed to
determine the number and location of the sentinel node(s).
Intraoperatively, after anesthetizing the patient, sentinel node biopsy will be
performed. During the first 15 min only fluorescence guidance will be used. If
this does not result in sentinel node identification, the conventional approach
of radio- and fluorescence and blue dye guidance will be used.
Ex vivo, for each removed sentinel node, the gamma probe status (amount of
radioactivity in the node) and the fluorescence status (y/n fluorescence in the
node) will be documented. Sentinel nodes will be assessed following the
standard sentinel node protocol at the department of pathology department.
Subsequently, after completion of the operation, the operating surgeon will be
asked to fill in a questionnaire to evaluate the value of fluorescence guidance
during the operation.

The value of fluorescence guidance during the sentinel node biopsy procedure
will be evaluated. Findings will be compared to the conventional approach.

Because initially sentinel nodes will be pursued using fluorescence guidance
only, anesthesia will be prolonged with 15-20 min.