Background: Superparamagnetic iron oxide nanoparticles (SPIO) have been used as a tracer for sentinel lymph node (SLN) localization in breast cancer, demonstrating comparable performance to the combination of radioisotope (RI) and blue dye (BD).

Methods: A systematic literature search and meta-analysis with subgroup and meta-regression analysis were undertaken to update the available evidence, assess technique evolution, and define knowledge gaps. Recommendations were made using the GRADE approach.

Results: In 20 comparative studies, the detection rate was 97.5 per cent for SPIO and 96.5 per cent for RI +/- BD (risk ratio 1.006, 95 per cent c.i. 0.992 to 1.019; P = 0.376, high-certainty evidence). Neoadjuvant therapy, injection site, injection volume or nodal metastasis burden did not affect the detection rate, but injection over 24 h before surgery increased the detection rate on meta-regression. Concordance was 99.0 per cent and reverse concordance 97.1 per cent (rate difference 0.003, 95 per cent c.i. -0.009 to 0.015; P = 0.656, high-certainty evidence). Use of SPIO led to retrieval of slightly more SLNs (pooled mean 1.96 versus 1.89) with a higher nodal detection rate (94.1 versus 83.5 per cent; RR 1.098, 1.058 to 1.140; P < 0.001; low-certainty evidence). In meta-regression, injection over 24 h before surgery increased the SPIO nodal yield over that of RI +/- BD. The skin-staining rate was 30.8 per cent (very low-certainty evidence), and possibly prevented with use of smaller doses and peritumoral injection.

Conclusion: The performance of SPIO is comparable to that of RI +/- BD. Preoperative injection increases the detection rate and nodal yield, without affecting concordance. Whether skin staining and MRI artefacts are reduced by lower dose and peritumoral injection needs to be investigated.

Importance  Guidewires have been the standard for breast lesion localization but pose operative and logistic challenges. Paramagnetic seeds have shown promising results, but to the authors’ knowledge, no randomized comparison has been performed.

Objective  To determine whether the combination of a paramagnetic seed and superparamagnetic iron oxide (SPIO) is equivalent to guidewire and SPIO for breast cancer localization and sentinel lymph node detection (SLND).

Design, Setting, and Participants  This was a phase 3, pragmatic, equivalence, 2-arm, open-label, randomized clinical trial conducted at 3 university and/or community hospitals in Sweden from May 2018 to May 2022. Included in the study were patients with early breast cancer planned for breast conservation and SLND. Study data were analyzed July to November 2022.

Interventions  Participants were randomly assigned 1:1 to a paramagnetic seed or a guidewire. All patients underwent SLND with SPIO.

Main Outcomes and Measures  Re-excision rate and resection ratio (defined as actual resection volume / optimal resection volume).

Results  A total of 426 women (median [IQR] age, 65 [56-71] years; median [IQR] tumor size, 11 [8-15] mm) were included in the study. The re-excision rate was 2.90% (95% CI, 1.60%-4.80%), and the median (IQR) resection ratio was 1.96 (1.15-3.44). No differences were found between the guidewire and the seed in re-excisions (6 of 211 [2.84%] vs 6 of 209 [2.87%]; difference, −0.03%; 95% CI, −3.20% to 3.20%; P = .99) or resection ratio (median, 1.93; IQR, 1.18-3.43 vs median, 2.01; IQR, 1.11-3.47; P = .70). Overall SLN detection was 98.6% (95% CI, 97.1%-99.4%) with no differences between arms (203 of 207 [98.1%] vs 204 of 206 [99.0%]; difference, −0.9%; 95% CI, −3.6% to 1.8%; P = .72). More failed localizations occurred with the guidewire (21 of 208 [10.1%] vs 4 of 215 [1.9%]; difference, 8.2%; 95% CI, 3.3%-13.2%; P < .001). Median (IQR) time to specimen excision was shorter for the seed (15 [10-22] minutes vs 18 [12-30] minutes; P = .01), as was the total operative time (69 [56-86] minutes vs 75.5 [59-101] minutes; P = .03). The experience of surgeons, radiologists, and surgical coordinators was better with the seed.

Conclusions and Relevance  The combination of SPIO and a paramagnetic seed performed comparably with SPIO and guidewire for breast cancer conserving surgery and resulted in more successful localizations, shorter operative times, and better experience.

Trial Registration  ISRCTN.org Identifier: ISRCTN11914537

Background: Superparamagnetic iron nanoparticles perform comparably to radioisotope +/- blue dye for sentinel lymph node detection in breast cancer, even when injected up to 8 weeks before surgery. Using superparamagnetic iron nanoparticles for sentinel lymph node detection after primary systemic therapy, and the maximum time frame of superparamagnetic iron nanoparticle administration have not been investigated.

Methods: This cohort study included cN0/1-to-ycN0 patients undergoing sentinel lymph node detection or targeted axillary dissection. All patients received superparamagnetic iron nanoparticles either before primary systemic therapy or before surgery, and radioisotope on the day of surgery.

Results: For 113 patients analysed, superparamagnetic iron nanoparticles were injected a median of 3 (range 0-248) days before surgery, with a 97.4% detection rate compared with 91.2% for radioisotope (P = 0.057). Concordance for radioisotope was 97.1% and this was not affected by timing of superparamagnetic iron nanoparticle injection (Kendall's tau 0.027; P = 0.746). The median sentinel lymph node yield was 3 (interquartile range (i.q.r.) 2-3) for superparamagnetic iron nanoparticles and 2 (i.q.r. 2-3) for radioisotope (P < 0.001). In targeted axillary dissection, detection was 100% for superparamagnetic iron nanoparticles and 81.8% for radioisotope (P = 0.124). The index node was magnetic in 93.9% and radioactive in 66.7% (P = 0.007), an outcome that was not affected by any factors. For patients with metastases, superparamagnetic iron nanoparticle detection was 100% and radioisotope-based detection was 84.2% (P = 0.083), with superparamagnetic iron nanoparticles detecting more metastatic sentinel lymph nodes (median of 1 (i.q.r. 1-2) for superparamagnetic iron nanoparticles compared with a median of 1 (i.q.r. 0-1) for radioisotope; P = 0.005).

Conclusion: Injection before primary systemic therapy is feasible and does not affect concordance with radioisotope. Superparamagnetic iron nanoparticles perform comparably to radioisotope, but detect more sentinel lymph nodes and have a higher rate of detection of metastatic sentinel lymph nodes.