The bilateral sentinel node detection rate of fluorescent indocyanine green compared to 99mTc and blue dye in the sentinel node procedure in stage I-IIA cervical cancer

Rationale: We hypothesize intraoperative indocyanine green (ICG) with near-infrared (NIR) fluorescence imaging provides non-inferior bilateral detection rates of sentinel lymph nodes (SLNs) in early-stage cervical cancer compared with the current standard of care, Technetium-99m nanocolloid (99mTc) with preoperative SPECT-CT in combination with intraoperative blue dye. In daily practice, switching to ICG offers advantages over the use of 99mTc and blue dye; ICG is cheaper, non-radioactive, logistically more attractive, and leads to less burden on the patient (shorter admission, injection under anaesthesia, potentially less morbidity).

Objective: To evaluate the bilateral SLN detection rate of intraoperative ICG with NIR fluorescence imaging compared to the current standard of care of 99mTc (with preoperative SPECT/CT) and blue dye.

Study design: We plan a cross-sectional, monocentre, non-inferiority study with a paired comparison of both SLN modalities in a single sample of patients. Thus, all patients undergo mapping with ICG and NIR fluorescence imaging followed by mapping with 99mTc and blue dye. The surgeons will be blinded for the pre-operative outcome of SPECT-CT to avoid biased detection with ICG.

Study population: Patients with early-stage cervical cancer who receive primary surgical treatment (FIGO stage IA – IB2 or IIA1).

Intervention: SLN procedure with NIR fluorescence imaging after peritumoural injection of ICG (5mg) in adjunct to the current standard of care.

Main study parameters/endpoints: The main endpoint of this study is bilateral SLN detection rate of the different modalities (i.e. detection of at least one SLN in each hemipelvis). Secondary endpoints include overall SLN detection rate (i.e. detection of at least one SLN), diagnostic accuracy in terms of tumour positivity of the different modalities (sensitivity and false negatives; defined as patients with tumour-negative SLNs and tumour-positive non-SLNs), with pelvic lymph node dissection (PLND) as gold standard to confirm tumour positive lymph nodes (part of current standard-of-care), the number of SLNs detected, concordance of SLN localisation with different modalities, cost-effectiveness in terms of costs related to the percentage increase in bilateral detection rate, patient satisfaction, and usability of fluorescence guided surgery.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: As we compare strategies for SLN procedure that are already applied in current daily practice (99mTc with blue dye) or on large scale in research setting for cervical cancer (ICG), no additional risks or burdens are expected from these interventions. Since ICG with NIR fluorescence imaging is used in adjunct to the standard procedure, the total operation time might be slightly longer (estimated at 15 minutes). The extra time will only be a small fraction of the total duration of the operation (240 minutes) and will therefore entail only minimal risks of prolonged anaesthesia. In very rare cases an allergic reaction to ICG has been reported (< 1/10.000 cases). In order to minimize this risk, patients with an severe allergy for iodine and those with a renal insufficiency are excluded from this study.
Patients receive an additional questionnaire (EORTC IN-PATSAT32) regarding patients’ satisfaction with the oncological care and services.1 This questionnaire is validated and the results can help us to place the outcome measures in context of the patients’ experience. No additional blood samples, site visits or physical examinations are needed during this study.
 

Intraoperative ICG with NIR fluorescence imaging provides non-inferior bilateral detection rates of SLNs in early-stage cervical cancer compared with the current standard of care, 99mTc and blue dye.

Intraoperative and postoperative (pathological assessment) measurements

SLN procedure with NIR fluorescence imaging after peritumoral injection of ICG (5mg) in adjunct to the current standard of care