Indocyanine green fluorescence versus blue dye, technetium-99M, and the dual-marker combination of technetium-99M + blue dye for sentinel lymph node detection in early breast cancer-meta-analysis including consistency analysis

Abstract

Background: Axillary sentinel lymph node biopsies are standard of care in patients with breast cancer and no clinically apparent metastases. Traditionally, technetium-99m, blue dye, or both have been used to identify sentinel lymph nodes. However, blue dyes miss up to 40% of sentinel lymph nodes, while technetium-99m use is complex, costly, and exposes patients to radiation. Over the past decade, studies have consistently found the biologically inert fluorescent indocyanine green to be 95% to 100% sensitive in detecting breast cancer sentinel lymph nodes, yet indocyanine green remains infrequently used.

Methods: We conducted an extensive meta-analysis comparing indocyanine green against blue dye, technetium-99m, and the dual-marker combination of technetium-99m + BD. Unlike prior meta-analyses that only assessed either per-case or per-node sentinel lymph node detection, we analyzed the following 5 metrics: per-case and per-node sentinel lymph node detection and metastasis-positive sentinel lymph node sensitivity, and mean number of sentinel lymph nodes/case. We further examined the consistency and magnitude of between-study superiority and statistically significant within-study superiority of each marker against others.

Results: For every metric and analysis approach, indocyanine green was clearly superior to blue dye and at least non-inferior, if not superior, to technetium-99m and technetium-99m + blue dye. Assessing the consistency of superiority by at least 2.0%, indocyanine green was superior to blue dye 73 times versus 1, to technetium-99m 42 times versus 9, and to technetium-99m + blue dye 6 times versus 0. Within-study statistically significant differences favored indocyanine green over blue dye 29 times versus 0 and over technetium-99m 11 times versus 2.

Discussion: For sentinel lymph node detection in patients with breast cancer with no clinically apparent metastases, indocyanine green is clearly and consistently superior to blue dye and either non-inferior or superior to technetium-99m and technetium-99m + blue dye.