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+(R) and the dual technique for SLN detection. 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+(R)) in 3 mL NaCl was used. In this dose-optimizing study, lower doses of a new refined SPIO solution (Magtrace(R)) (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(R) 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. Funding Agencies|Uppsala University; Vastmanland Cancer Foundation