Frumovitz M, et al. - Given that accurately identifying sentinel lymph nodes in cancer patients improves detection of metastatic disease and reduces surgical morbidity, researchers investigated if indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in distinguishing sentinel lymph nodes in women with cervical and uterine cancers. They found that more sentinel nodes were found with indocyanine green dye with near-infrared fluorescence imaging vs isosulfan blue dye, with no difference in the pathological confirmation of nodal tissue between the two mapping substances.

Methods

• This is a non-inferiority, within-patient comparison study with patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery.
• Participants were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualized by white light) followed by indocyanine green (visualized by near-infrared imaging), or indocyanine green followed by isosulfan blue dye.
• Using a computerized random number generator, they performed permuted block randomization with stratification by study site.
• Investigators were not masked to the procedure used but, until after the procedure, all participants were masked to their randomization assignment.
• In all cases, they used laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI).
• They assessed the efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging vs that of isosulfan blue dye in the identification of lymph nodes (primary outcome), defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised.
• A 5% non-inferiority margin was required in this study to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level.
• Both per-protocol and modified intention-to-treat populations were analyzed.

Results

• Enrollment of 180 patients was carried out between December 21, 2015 and June 19, 2017.
• These subjects were randomized to the two groups (90 to each group); the intervention was received by 176 patients, and these were evaluable (modified intention-to-treat population).
• From the per-protocol population, 13 patients with major protocol violations were subsequently excluded.
• The per-protocol population (n=163) was found to have 517 sentinel nodes; pathological processing confirmed 478 (92%) of these as lymph nodes: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0.33).
• Neither blue nor green were seven sentinel lymph nodes, but these were removed for appearing suspicious or enlarged on visual examination.
• Overall, the green dye identified 471 (97%) of 485 lymph nodes and the blue dye detected 226 (47%) lymph nodes (difference 50%, 95% CI 39–62; p < 0.0001).
• A total of 545 nodes were identified in the modified intention-to-treat population (n=176), with pathological processing confirming 513 (94%) of these as lymph nodes: 229 (92%) of 248 nodes that were both blue and green, all nine nodes that were blue only, and 266 (95%) of 279 nodes that were green only (p=0.30).
• Data showed that nine sentinal lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination.
• The green dye identified 495 (96%) of 513 nodes and 238 (46%) were identified with the blue dye (50%, 39–61; p < 0.0001).