Magnetic Seed vs Guidewire Breast Cancer Localization With Magnetic Lymph Node Detection: A Randomized Clinical Trial.

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.

A Comparison of Skin Staining after Sentinel Lymph Node Biopsy in Women Undergoing Breast Cancer Surgery Using Blue Dye and Superparamagnetic Iron Oxide Nanoparticle (SPIO) Tracers.

Superparamagnetic iron oxide nanoparticles (SPIO) are a tracer for sentinel lymph node (SLN) detection. In a preplanned secondary analysis of a prospective clinical trial (SentiDose) we reported on skin staining after SPIO and blue dye (BD) injections. For SPIO, either a 1.5 mL retroareolar injection on the day of surgery or a 1.0 mL peritumoral/retroareolar injection 1-7 days before surgery was given. A 1.0 mL sub-/intradermal periareolar injection of BD was also administered to all these women. Staining was then assessed at 6, 12 and 24 months after surgery. A total of 270 women received SPIO and were operated on with breast-conserving surgery. Of these, 204 women also received BD. A total of 58 (21.5%) women had an SPIO stain 6 months postoperatively with a median size of 6.8 cm2 (p = 0.56), while 51 (25.0%) had a BD stain with a median size of 8.5 cm2 (p = 0.93). The incidence and size of SPIO and BD staining decreased over time reciprocally. At 24 months, the incidence and median size of SPIO was 23 (8.6%) and 4 cm2, respectively. For BD, the incidence was 14 (6.3%, p = 0.13), and the median size was 3.5 cm2 (p = 0.18). There was, therefore, no statistically significant difference in the incidence or size of skin staining between SPIO and BD over time.

Optimizing Dose and Timing in Magnetic Tracer Techniques for Sentinel Lymph Node Detection in Early Breast Cancers: The Prospective Multicenter SentiDose Trial.

Superparamagnetic iron oxide nanoparticles (SPIO) are non-inferior to radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) detection. Previously, 2 mL SPIO (Sienna+®) in 3 mL NaCl was used. In this dose-optimizing study, lower doses of a new refined SPIO solution (Magtrace®) (1.5 vs. 1.0 mL) were tested in different timeframes (0-24 h perioperative vs. 1-7 days preoperative) and injections sites (subareolar vs. peritumoral). Two consecutive breast cancer cohorts (n = 328) scheduled for SLN-biopsy were included from 2017 to 2019. All patients received isotope ± blue dye as back-up. SLNs were identified primarily with the SentiMag® probe and thereafter a gamma-probe. The primary endpoint was SLN detection rate with SPIO. Analyses were performed as a one-step individual patient-level meta-analysis using patient-level data from the previously published Nordic Trial (n = 206) as a third, reference cohort. In 534 patients, the SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 and the 2.0 mL cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Lower SPIO volumes injected up to 7 days before the operation have comparable efficacy to standard SPIO dose and RI + BD for SLN detection.

A combined, totally magnetic technique with a magnetic marker for non-palpable tumour localization and superparamagnetic iron oxide nanoparticles for sentinel lymph node detection in breast cancer surgery.

BACKGROUND: Surgery for non-palpable breast cancer may often be a challenging procedure. Recently, a magnetic seed (Magseed®) used for tumour localization has been developed. Superparamagnetic iron oxide nanoparticles (SPIO) for sentinel lymph node (SN) detection is a novel tracer that may be injected up to four weeks preoperatively. This study is the first combining the magnetic seed and SPIO. MATERIAL AND METHODS: Patients planned for breast conserving surgery and SN-biopsy (SNB) were recruited from two units in Sweden. Patients underwent lesion localization with Magseed® and SPIO injection (Magtrace™) by the breast radiologist in the preoperative period. Feasibility of successful lesion localization and excision together with a successful SNB detection was evaluated. Seed migration, number of SNs, specimen volume and calculated resection ratio (CRR) were reported.A survey of the physicians' experience was conducted. RESULTS: Localization was performed at a median of three days before surgery (range 0-25). All 32 patients underwent microscopically radical resection with a CRR of 1.49. No seed migration was noticed. SNB was successful in all patients. A median of two SNs was retrieved. Radiologists and surgeons reported the procedure easy to learn and outperformed guidewire localization in terms of localization and excision time. They thought the technique facilitated planning localization and surgery. CONCLUSIONS: The combined magnetic technique provided accuracy in tumour localization and SN detection without excess tissue excision and with promising results for flexibility in delivery of care. Larger studies are needed to confirm these findings.