DOI: 10.1097/js9.0000000000005686 ISSN: 1743-9159

Comparative diagnostic performance and safety of indocyanine green versus superparamagnetic iron oxide and Technetium-99m for sentinel lymph node biopsy in breast cancer: a systematic review and meta-analysis

Tessa L. Dinger, Patrick E. Goldhawk-White, Kevin P. White, Gabriela Pilz da Cunha, Vassilis Pitsinis, Annemiek Doeksen
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Background:

Technetium-99 m ( 99m Tc) is the current standard of care for sentinel lymph node (SLN) biopsy in early breast cancer. Non-radioactive alternatives such as indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) compounds have demonstrated non-inferior and, in some studies, superior SLN detection rates compared with 99m Tc. Given that ICG offers safety advantages over SPIO, it is important to understand their comparative performance. As no studies have directly compared ICG and SPIO, this study aimed to indirectly compare these tracers through separate comparisons with 99m Tc.

Materials and methods:

Two systematic reviews and meta-analyses were conducted, comparing ICG versus 99m Tc and SPIO versus 99m Tc. An indirect comparison of ICG and SPIO assessed non-inferiority and superiority. Primary outcomes were per-case and per-node SLN detection and sensitivity for pathological SLNs, presented as odds ratios (ORs) with 95% confidence intervals (CIs). Secondary outcomes included tracer-related adverse events.

Results:

Across 26 studies, ICG ( n = 3105) outperformed 99m Tc ( n = 3219) in per-case detection (OR = 1.48; 95% CI: 1.00–2.19; P = 0.049), per-node detection (OR = 4.00; 95% CI: 2.00–8.01; P < 0.001), and pathological sensitivity (OR = 2.35; 95% CI: 1.50–3.68; P < 0.001). Meta-analysis of 20 studies showed that SPIO ( n = 2093) was superior to 99m Tc ( n = 2092) only for per-node detection (OR = 1.59; 95% CI: 1.06–2.39; P = 0.025). Indirect comparison showed that ICG was superior to SPIO for both per-case ( P = 0.005) and per-node detection ( P < 0.001), with non-inferior pathological sensitivity. No ICG-related adverse events were reported, whereas SPIO caused bronze skin staining in 23.4% of patients ( P < 0.001).

Conclusion:

ICG demonstrated superior diagnostic performance compared with both 99m Tc and SPIO, and was associated with fewer tracer-related adverse events than SPIO. However, direct comparisons between ICG and SPIO are needed to strengthen this conclusion.

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