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

SIMPLE SUMMARY: Superparamagnetic iron oxide (SPIO) nanoparticles have comparable performance to the combination of radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) biopsy in breast cancer. In this multicenter prospective study, lower SPIO doses (undiluted 1.5 vs. 1.0 mL) in different timeframes (perioperative vs. 1–7 days preoperative) and injection sites (subareolar vs. peritumoral) were compared to the previous standard (diluted 2.0 mL perioperatively) from the earlier Nordic trial. RI + BD were co-administered as background. In total, 534 patients were analyzed. SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and respectively non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 mL and the Nordic cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Thus, SPIO at 1.5 and 1.0 mL was non-inferior to both Sienna+(®) and the dual technique for SLN detection. ABSTRACT: 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.