Sentinel Lymph Node Biopsy in Vulvar Cancer Using Combined Radioactive and Fluorescence Guidance

Abstract

Objective: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has recently been introduced to improve the sentinel lymph node (SLN) procedure. Several optical tracers have been successfully tested. However, the optimal tracer formulation is still unknown. This study evaluates the performance of ICG-technetium-99m (99mTc)-nanocolloid in relation to 2 most commonly used ICG-based formulas during SLN biopsy in vulvar cancer.

Methods and materials: Twelve women who planned to undergo SLN biopsy for stage I vulvar cancer were prospectively included. Sentinel lymph node mapping was performed using the dual-modality radioactive and NIR fluorescence tracer ICG-99mTc-nanocolloid. All patients underwent combined SLN localization using NIR fluorescence and the (current) gold standard using blue dye and radioactive guidance.

Results: In all 12 patients, at least 1 SLN was detected during surgery. A total of 21 lymph nodes (median 2; range, 1-3) were resected. Median time between skin incision and first SLN detection was 8 (range, 1-22) minutes. All resected SLNs were both radioactive and fluorescent, although only 13 (62%) of 21 SLNs stained blue. Median brightness of exposed SLNs, expressed as signal-to-background ratio, was 5.4 (range, 1.8-11.8). Lymph node metastases were found in 3 patients.

Conclusions: Near-infrared fluorescence-guided SLN mapping is feasible and outperforms blue dye staining. Premixing ICG with 99mTc-nanocolloid provides real-time intraoperative imaging of the SN and seems to be the optimal tracer combination in terms of intraoperative detection rate of the SN (100%). Moreover, ICG-99mTc-nanocolloid allows the administration of a 5-times lower injected dose of ICG (compared with ICG and ICG absorbed to human serum albumin) and can be injected up to 20 hours before surgery.

FIGURE 1. Preoperative SLN mapping

Example of SLN mapping using lymphoscintigraphy and SPECT/CT after administration of ICG:^99mTc-nanocolloid. A: lymphoscintigraphy showing the injection spot and one SLN in the left groin. B, C, D and E: fused SPECT/CT images showing the position of the SLN in relation to patient anatomy. SLN= Sentinel Lymph node, inj.: Injection spot.

FIGURE 2. NIR fluorescence-guided sentinel lymph node (SLN) mapping

Intraoperative NIR fluorescence guided SLN mapping performed in the same patient as figure 1, using ICG:^99mTc-nanocolloid. Top row, percutaneous NIR identification of afferent lymphatic channels flowing away from the injection site (Inj.). The planned incision site, based on the presumed location of the SLN, is shown as a dashed line. Middle row, real-time fluorescence identification of the SLN directly after incision. Bottom row, SLN resection under fluorescence guidance. Scale bars = 1 cm. Camera exposure times were: 100 msec (upper and middle row) and 60 msec (bottom row).

FIGURE 3. Time between skin incision and SLN detection

Shown is the effect of Body Mass Index (BMI) (abscissa) on skin incision to SLN identification time (ordinate) in the context of ICG preparation method. Points represent individual patients. Green circles represent patients that received ICG alone; blue circle represents patients that received ICG:HSA; and red circles represents patients that received ICG:^99mTc-nanocolloid. Dotted line represents the median for each group.

FIGURE 4. Signal-to-Background ratios between study protocols

The signal-to-background ratios of the different formulations is shown as mean with range: ICG alone (0.62 mg; 1.6 mL; injected during surgery), ICG:HSA (0.62 mg; 1.6 mL; injected during surgery) and ICG-^99mTc-nanocolloid (0.05 mg; 0.4 mL; injected up to 20h prior to surgery).