SLN Detection with Fluorescence Imaging for Uterine and Cervical Cancer

Over the past decade, Memorial Sloan Kettering has led the way in demonstrating the value of detecting sentinel lymph node (SLN) involvement in cervical and uterine cancers. The Gynecology Service opened its first clinical trial in SLN mapping for cervical cancer in 2003, followed by an endometrial cancer protocol in 2005.

Gynecologic surgeon Nadeem Abu-Rustum has led our program in SLN mapping and taught many physicians around the country and the world the importance and value of incorporating this technique into clinical practice.

New Technologies

Traditionally, SLNs have been detected using blue dyes (methylene blue or isosulfan blue). New technologies, such as near-infrared (NIR) imaging and the use of fluorescent dyes, have enabled us to identify these nodes more easily.  

For example, the fluorescent dye indocyanine green (ICG) makes the SLN glow like a firefly under NIR imaging (Figure 1).

Indocyanine green and near-infrared imaging to visualize the sentinel lymph node. Enlarge Image Figure 1 Indocyanine green and near-infrared imaging to visualize the sentinel lymph node. Large panel: “Green” left external iliac sentinel lymph node visualized with the PINPOINT endoscopic fluorescence assessment; left upper panel: regular laparoscopy image after injection of green dye; left middle panel: left external iliac sentinel lymph node shown with near-infrared imaging (NIR); left lower panel: left external iliac sentinel lymph node shown with the PINPOINT endoscopic fluorescence assessment.

In December 2011, following clinical trials testing through our Robotics Program by gynecologic oncologist Mario Leitao, Memorial Sloan Kettering incorporated NIR imaging systems into clinical care.

Since then, we have used the NIR system in more than 250 cases. SLN detection rates have subsequently risen, from 85 percent to 95 percent.(1)More importantly, our bilateral pelvic mapping rate is now approximately 79 percent compared to an historic bilateral mapping rate of 40 percent.(1)(2)

Excision of sentinel lymph node after visualization with indocyanine green and near-infrared imaging. Enlarge Image Figure 2 Excision of sentinel lymph node after visualization with indocyanine green and near-infrared imaging. Large panel: “Green” left external iliac sentinel lymph node shown after excision using the PINPOINT endoscopic fluorescence assessment; left upper panel: same sentinel lymph node shown with regular laparoscopic image; left middle panel: same sentinel lymph node shown with near-infrared imaging (NIR); left lower panel: same as large panel.

Analysis

In 2014, gynecologic surgeon Elizabeth Jewell and colleagues reported on the MSK experience in SLN mapping using ICG and NIR fluorescence imaging in 227 patients with cervical or uterine cancer.(1) The majority of patients (138 of 227, or 61 percent) were diagnosed with grade 1 or 2 endometrioid adenocarcinoma of the uterus.

The median surgical time to complete the SLN mapping was 30 minutes, with some patients being mapped within three minutes (range: three to 84 minutes). The median number of SLNs removed was three (range: one to 23). ICG dye alone was used in 87 percent of cases (n=197), and ICG and blue dye was used in 13 percent of cases (n=30).

The overall detection rate of the SLN (unilaterally or bilaterally) for this cohort of patients was 95 percent (216 of 227). An SLN was not identified in 11 cases. In cases in which only ICG was used, 95 percent (188 of 197) mapped either unilaterally or bilaterally, compared to 93 percent (28 of 30) of cases in which both the ICG and blue dyes were used (P=NS). The bilateral detection rate was 79 percent overall (179 of 227). The bilateral SLN detection rate for ICG alone was 79 percent (156 of 197) compared to 77 percent (23 of 30) for ICG and blue dye (P=NS).

The median BMI of patients who mapped was 30.1 kg/m2 (range: 17.7-59.6 kg/m2) compared to 41.2 kg/m2 (range: 25.1-60.4 kg/m2) for patients who did not map (P=0.01). Median BMI appeared to impact bilateral mapping, with the median BMI of unilaterally and bilaterally mapped cases being 34 kg/m2 (range: 17.9-49 kg/m2) and 29.6 kg/m2 (range: 17.7-59.6 kg/m2) respectively (P=0.02).(1)

The clinical relevance of this finding is that fewer patients may need a hemi-pelvic lymph node dissection to assess nodal status, especially if SLN mapping is ultimately validated as an acceptable alternative to lymphadenectomy.

Next Steps

The future of SLN research includes trying to identify SLNs with disease in vivo. Drs. Jewell and Abu-Rustum are incorporating the use of nanoparticles and antibodies to tag cancer cells and see if they can be identified in the SLN in vivo during an operation.

If we can predict in vivo if lymph nodes are positive, we may be able to identify which patients will benefit from additional treatment without the removal of lymph nodes and thereby minimize the risk for lower extremity lymphedema.

These techniques are also being considered for the detection of inguinual-femoral lymph nodes in vulvar cancer. We are undertaking ongoing cost analysis projects to examine cost-effective strategies for lymph node removal in cancer care.

  1. Jewell EL, Huang JJ, Abu-Rustum NR, et al. Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-infrared fluorescence imaging for uterine and cervical malignancies. Gynecol Oncol 2014; 133:274-7.
  2. Leitao Jr MM, Khoury-Collado F, Gardner GJ, et al. Sentinel lymph node mapping in patients with endometrial cancer undergoing robotically assisted or standard laparoscopic procedures. Presented at the 2011 Society of Gynecologic Oncology 42nd Annual Meeting on Women's Cancer. March 6-9, 2011. Orlando, FL.