Magnetic and indocyanine green (ICG) sentinel lymph node mapping in colorectal cancer: A feasibility and validity clinical trial.

31 Background: This is a single center, open label, side-by-side comparator study to assess the safety, feasibility and validity of lymphatic staging using the standard of care lymphadenectomy and histopathology process compared with using FerroTrace with or without ICG for mapping sentinel lymph nodes (SLNs) as an adjunct to the standard of care lymphadenectomy in subjects with colorectal cancer. Application of sentinel lymph node mapping in colorectal cancer has the potential to facilitate ultra-staging to accurately identify nodal metastases. However, SLN biopsy techniques are not established for colorectal surgery because of a lack of practical tracers; an effective and convenient tracer that exclusively accumulates in SLNs is critically needed. Methods: Eligible subjects (n=18) received a single dose of FerroTrace and a single dose of ICG via four endoscopic peri-tumoral submucosal injections into the colorectal tissue, either separately for subjects part of the MRI protocol (), or together for those not including MRI (colon). Intraoperative laparoscopic fluorescence imaging was used to highlight draining lymphatic pathways containing ICG(n=3), while a combination of T1/T2-weighted MRI and magnetometer probe detection were used to identify nodes containing SPIONs in the lateral pelvic wall. Histopathology was conducted as per standard of care for all LNs in the lymphadenectomy specimen, plus more detailed ultra-staging of SLNs using serial slicing and immunochemistry. Results: On average 4 SLN nodes (range 0–8) and 18.5 non-SLN nodes were detected (range 7–48). Magnetic nodes could be identified using both preoperative MRI and intraoperative magnetometer probe. False Negative Rate (FNR) = 0% Negative Predictive Value = 100% Overall Accuracy=100 % SLN Upstaging Rate =20% (patient level). No FerroTrace related adverse events (AEs) were noted. Conclusions: Through the co-injection of fluorescent and magnetic tracers, lymphatic drainage pathways can be determined preoperatively with MRI (rectal cancer), visualized with intraoperative fluorescence cameras, and SLNs confirmed with magnetometer (all cases). The high accuracy rate and 0% False Negative Rate demonstrates that this is a very promising tool to guide surgical decision making in colorectal cancer. The upstaging rate with FerroTrace guided ultra-staging, highlighted that SOC pathology was missing small tumor deposits in the high risk nodes draining the tumor. Clinical trial information: ACTRN12621000748819 .