Indocyanine Green Fluorescence for Sentinel Lymph Node Detection in Early Breast Cancer.

Abstract

In this issue of Annals of Surgical Oncology, Sugie and colleagues report results of a prospective multicenter cohort study that further validates and assesses the accuracy of indocyanine green (ICG) for identification of sentinel lymph nodes (SLNs) in early breast cancer patients. SLN biopsy using the fluorescent tracer ICG combined with radioisotope avoids the need for blue dye and thereby minimizes potential morbidity, including cutaneous staining and allergic/anaphylactic reactions. Within the past 3–4 years there has been a significant increase in reports of allergic reactions to blue dye. The Medicines and Healthcare products Regulatory Agency (MHRA) issued a drug safety update in February 2012 emphasizing that the occurrence of allergic reactions to blue dye was not uncommon and was estimated to have an incidence of 0.1 % in the Axillary Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) trial. In light of these recent concerns, there has been a trend away from the use of blue dye for SLN localization, and ICG as a tracer agent may serve as an adjunct to radioisotope in the first instance. This technology relies on generation of molecular fluorescence by contact of ICG with plasma proteins in the lymphovascular system. This fluorochrome absorbs light at a wavelength of approximately 800 nm with emission of a fluorescent signal when subatomic particles return from an excited to ground state. The illuminated subcutaneous lymphatic channels can be seen on a photodynamic eye (PDE) camera display and ICG tracked as it passes towards the axilla. The fluorescence is scattered by superficial tissues and cannot be detected at a depth of more than 1 cm with current equipment. The visual dimension of fluorescence with high optical sensitivity is a great advantage to radioisotope alone and could be complementary to radioisotope in the absence of blue dye. A recently published systematic review found that ICG was more accurate than blue dye for SLN identification (odds ratio [OR] 18.37; 95 % CI 8.83–39.10), with no statistically significant difference between ICG and radiocolloid for this metric (OR 0.81; 95 % CI 0.03–24.29). This review highlighted the wide range of ICG doses used amongst studies, and standardization of dosage in terms of concentration and volume of ICG is essential to optimize performance of this technology. Nonetheless, there are potential drawbacks from the use of radioisotopes as a tracer agent for SLN localization, including cumulative radiation exposure for healthcare workers, issues with surgical waste disposal, and restrictions on access to radioisotopes secondary to mandatory licensing. Radioactive technetium-based nanocolloid is usually injected a few hours preoperatively in a dedicated nuclear medicine facility and requires a coordinated effort between different disciplines. Moreover, these radioisotopes are a by-product of a contracting nuclear industry, and supply might become unpredictable with more widespread usage, particularly within emerging economies of Asia. Therefore, potential problems exist with both standard tracer agents, and exploration of alternative, nonradioactive agents such as ICG and magnetic particles is warranted. This is the largest study published to date assessing the accuracy of ICG for SLN identification. A total of 821 patients were available for final analysis from 12 centers throughout Japan, with all patients receiving a combination of fluorescent ICG and Tc nanocolloid for localization. The authors chose as their primary endpoint the sensitivity Society of Surgical Oncology 2015