A green fluorescent dye beat the standard blue dye for mapping lymph nodes when the two were compared directly in women with uterine or cervical cancers. The finding comes from a phase 3 noninferiority trial, known as Fluorescence Imaging for Lymphatic Mapping (FILM)
The results showed not only that indocyanine green fluorescent dye was noninferior to isosulfan blue dye when used in conjunction with near-infrared imaging but also that it was significantly better than the standard-issue blue dye in identifying more sentinel nodes and more lymph nodes with metastases in women with uterine cancers.
The study was published online August 21 in the Lancet Oncology. "Accurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity," Michael Frumovitz, MD, University of Texas MD Anderson Cancer Center, Houston, and colleagues write.
"If [indocyanine green fluorescent dye] is approved for on-label use, it will hopefully become the new standard of care for lymphatic mapping and sentinel lymph node biopsy for women with cervical and uterine cancers," they suggest.
In a linked commentary, Maria Luisa Gasparri, MD, University Hospital of Bern and the University of Bern, Switzerland, and colleagues observe that sentinel lymph node mapping has long been a topic of interest in uterine malignancies. However, "it was only first considered an acceptable alternative to a systematic lymphadenectomy by international guidelines in 2014," she notes.
"Through its user-friendliness and effectiveness, indocyanine green is enabling surgeons to transition from systematic lymphadenectomy to sentinel lymph node biopsy," the editorialists suggest.
The findings from this study "confirm both the non-inferiority and superiority of indocyanine green compared with isosulfan blue dye as a new standard in sentinel lymph node mapping," they add.
FILM Trial Details
In the FILM trial, the researchers compared detection rates for sentinel nodes and sentinel nodes with metastatic disease for the two dyes, after they were administered by interstitial cervical injection in women with uterine or cervical cancer. Ninety-six percent of the group had uterine cancer, whereas only 4% had cervical cancer.
Participants were assigned to either lymph node mapping with isosulfan blue dye followed by lymph node mapping with indocyanine green dye and PINPOINT near-infrared imaging (Stryker) or lymph node mapping with indocyanine green dye and PINPOINT near-infrared imaging followed by lymph node mapping with isosulfan blue dye.
Ninety patients were assigned to each of the two groups. All surgeons involved in the study were proficient in the mapping procedure. The primary analytical cohort consisted of a total of 163 patients who made up the per-protocol cohort.
In the per-protocol cohort, a total of 517 nodes were identified intraoperatively, 92% of which were confirmed to be lymph nodes on pathology. The modified intention-to-treat population considered 176 patients, from whom 545 nodes were identified intraoperatively. Almost all of these were again confirmed to be lymph nodes on pathology.
As investigators report, the indocyanine green dye was "significantly superior" to the isosulfan blue bye in detecting at least one sentinel node as well as in detecting bilateral sentinel nodes.
The use of blue dye after the green dye was not needed, the researchers concluded, because it identified few additional sentinel nodes the green dye had not already detected.
Furthermore, the team notes that "all metastatic sentinel nodes were detected with indocyanine green, but more than a third would have been missed had isosulfan blue dye alone been used." The green dye was also safe, as no adverse events were noted, they add.
"For women with cervical and uterine cancers, increasing evidence suggests that lymphatic mapping and sentinel node biopsy not only improves detection of disease in regional nodes but also decreases operative morbidity," Frumovitz and colleagues conclude.