Near-infrared fluorescence imaging using indocyanine green as an adjunct to improve standard-of-care sentinel lymph node procedure in pediatric patients with melanoma or sarcoma of head/neck/trunk, paratesticular or extremities: a feasibility trial

The standard-of-care sentinel lymph node (SLN) procedure in paediatric cancer
patients consists of a preoperative intradermal injection with
99mTechnetium-nanocolloid as radiotracer in combination with an intraoperative
injection of blue dye for optical guidance. This method has been proven to
accurately detect the SLN in paediatric melanoma and sarcoma patients with a
detection rate of around 95% nowadays. To localize a SLN a radiotracer such as
99mTc-nanocolloid is essential, because successful SLN identification depends
on the radioactive signal detected by a handheld gamma probe. However,
disadvantages of using a radiotracer are the disturbance of the radioactive
signal originating from the injection site, a low spatial resolution and the
fact that the surgery has to be interrupted in order to use the gamma probe.
Consequently, it is sometimes difficult to find the true SLN. These limitations
of the radiotracer can be abolished by using at the same time an agent that
could aid optical guidance and does not interrupt the surgery. Therefore, if
deemed necessary, blue dye is currently used to optically support the surgeon
during the SLN procedure. However, the use of blue dye has evident
disadvantages such as risk of severe allergic reactions and long lasting
tattooing, in addition to the limited penetration depth and alteration of the
surgical field. Furthermore, the efficacy is low with only 60% of SLNs staining
blue.
In adult melanoma patients, near-infrared (NIR) fluorescence imaging using
indocyanine green (ICG) has been shown to be a safe, efficient and accurate
method for intra-operative visual identification of SLNs, with a higher
sensitivity (up to 97%) compared to blue dye. Furthermore, good safety profiles
are also established for the paediatric population, although for other
indications. Due to the high performance of ICG in adults and the good safety
and favourable side-effects profile of ICG compared to blue dye, we expect that
a combined intradermal injection of ICG noncovalently bound to
99mTc-nanocolloid (ICG-99mTc-nanocolloid) is able to retain or even improve the
optical guidance during surgery, while preventing the considerable risk of
side-effects when using blue dye.

To determine the feasibility of using ICG to optically guide the surgeon to the
SLN of paediatric melanoma and sarcoma patients. The SNP is a diagnostic
procedure.

A feasibility single-institution trial to assess the use of ICG combined with
99mTc-nanocolloid for the SLN procedure of paediatric patients with melanoma or
sarcoma of the extremity, paratesticular, head, neck or trunk. Standard-of-care
SLN procedure will be performed (99mTc-nanocolloid). ICG will be premixed with
99mTc-nanocolloid prior to injection (two separate agents). In accordance with
the standard-of-care SLN procedure, blue dye will be used in addition if deemed
necessary by the surgeon.

Using ICG in adjunct to the already used 99mTc-nanocolloid does not give any
extra burden for the patients, since no extra visits, physical examinations or
other tests, questionnaires or diaries, injections or blood samples are needed.
In addition, no significant risks were identified by our institutional
prospective risk analysis other than a very small risk (<1:10.000) of an
allergic reaction to ICG. In order to minimize this risk, patients with an
allergy for iodine and those with a renal insufficiency are excluded from this
study. Because of the favourable side-effect profile in addition to the
increased SLN identification of ICG compared to blue dye, ICG is currently used
as standard-of-care in many hospitals treating adult patients, showing the
evident potential benefit for paediatric patients. Furthermore, although the
use of the Quest NIR camera for this indication is outside its intended use, we
do not expect any additional risk, because the visualization method is similar
to tissue perfusion: its intended use.