Green is just as good – make that better – than blue at identifying sentinel lymph nodes in women with cervical and uterine cancers, results of the multicenter FILM (Fluorescence Imaging for Lymphatic Mapping) study indicate.
Among 176 patients randomly assigned to first have lymphatic mapping with indocyanine green fluorescent dye visualized with near infrared imaging followed by isosulfan blue dye visualized with white light, or the two modalities in the reverse order, indocyanine green identified 50% more lymph nodes in both modified intention-to-treat and per-protocol analyses, reported Michael Frumovitz, MD, from the University of Texas MD Anderson Cancer Center in Houston and colleagues.
“Indocyanine green dye with near-infrared imaging identified significantly more sentinel nodes and more bilateral sentinel nodes than did isosulfan blue dye. It also identified all sentinel nodes with metastatic disease, whereas isosulfan blue dye missed a large proportion of them,” they wrote in the Lancet Oncology.
The FILM study was designed to determine whether fluorescent indocyanine green dye would be noninferior to isosulfan blue dye for accurately identifying sentinel lymph nodes in patients with cancer.
Although several single-center retrospective studies have reported on the use of interstitial injection of indocyanine green for lymphatic mapping in various solid tumors, including uterine and cervical cancers, there were no published studies comparing indocyanine green mapping to isosulfan blue mapping, the standard of care, the authors noted.
They enrolled 180 women aged 18 or older with clinical stage I endometrial or cervical cancers who were undergoing curative surgery and randomly assigned them as described above to have lymphatic mapping with each of the imaging modalities assigned in random order.
The patients but not the operators were masked as to the order of randomization.
Of the 180 patients enrolled, 176 received the intervention, and 13 of these patients were excluded because of major protocol violations, leaving 163 for a per-protocol analysis.
In the per-protocol analysis, 517 sentinel nodes were identified in the 163 patients, and of these, 478 (92%) were confirmed to be lymph nodes on pathological examination. This sample included 219 of 238 nodes identified with both blue and green dyes, all seven nodes revealed by blue dye alone, and 252 of 265 nodes identified by only green dye. Seven sentinel lymph nodes that were not identified by either dye were removed because they were enlarged or appeared suspicious on visual inspection.
In total, green dye identified 97% of lymph nodes in the per-protocol population, and blue dye identified 47%, an absolute difference of 50% (P less than .0001).
In the modified intention-to-treat population, which included all 176 patients randomized and treated, 545 nodes were identified, and 513 (94%) were confirmed to be lymph nodes on pathology. In this sample, 229 (92%) of 248 nodes showed both blue and green, nine nodes were blue only, and 266 (95%) of 279 were green only. Nine sentinel lymph nodes that were not revealed by either blue or green were removed for appearing suspicious or enlarged visually.
In total, in the modified-ITT analysis, 495 of 513 (96%) nodes were identified with the green dye and 238 (46%) were identified with the blue dye, again for an absolute difference of 50% (P less than .0001).
Based on the results of the study, the green dye’s maker, Novadaq Technologies, is submitting an application to the Food and Drug Administration for on-label use of interstitial injection of indocyanine green combined with near-infrared imaging for lymphatic mapping.
The study was funded by Novadaq. Dr. Frumovitz reported grants from Novadaq/Stryker during the conduct of the study, as well as personal fees; grants from Navidea; personal fees from Johnson & Johnson; and personal fees from Genentech outside the submitted work. The other authors declared no competing interests.
SOURCE: Frumovitz M et al. Lancet Oncol. 2018 Aug 21. doi: 10.1016/S1470-2045(18)30448-0.