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

Abdi-Fatah Hersi, Lida Pistiolis, Carlos Dussan Luberth, Eva Vikhe-Patil, Fredrik Nilsson, Imad Mohammed, Roger Olofsson Bagge, Fredrik Wärnberg, Staffan Eriksson, Andreas Karakatsanis, Abdi-Fatah Hersi, Lida Pistiolis, Carlos Dussan Luberth, Eva Vikhe-Patil, Fredrik Nilsson, Imad Mohammed, Roger Olofsson Bagge, Fredrik Wärnberg, Staffan Eriksson, Andreas Karakatsanis

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.

Keywords: breast cancer; magnetic tracer; sentinel lymph node; sentinel lymph node biopsy; superparamagnetic iron oxide.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Veronesi U., Paganelli G., Viale G., Luini A., Zurrida S., Galimberti V., Intra M., Veronesi P., Robertson C., Maisonneuve P., et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N. Engl. J. Med. 2003;349:546–553. doi: 10.1056/NEJMoa012782.
    1. Del Bianco P., Zavagno G., Burelli P., Scalco G., Barutta L., Carraro P., Pietrarota P., Meneghini G., Morbin T., Tacchetti G., et al. Morbidity comparison of sentinel lymph node biopsy versus conventional axillary lymph node dissection for breast cancer patients: Results of the sentinella-GIVOM Italian randomised clinical trial. Eur. J. Surg. Oncol. 2008;34:508–513. doi: 10.1016/j.ejso.2007.05.017.
    1. Ashikaga T., Krag D.N., Land S.R., Julian T.B., Anderson S.J., Brown A.M., Skelly J.M., Harlow S.P., Weaver D.L., Mamounas E.P., et al. Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection. J. Surg. Oncol. 2010;102:111–118. doi: 10.1002/jso.21535.
    1. Lucci A., McCall L.M., Beitsch P.D., Whitworth P.W., Reintgen D.S., Blumencranz P.W., Leitch M., Saha S., Hunt K.K., Giuliano A.E. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011. J. Clin. Oncol. 2007;25:3657–3663. doi: 10.1200/JCO.2006.07.4062.
    1. Mansel R.E., Fallowfield L., Kissin M., Goyal A., Newcombe R.G., Dixon J.M., Yiangou C., Horgan K., Bundred N., Monypenny I., et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: The ALMANAC Trial. J. Natl. Cancer Inst. 2006;98:599–609. doi: 10.1093/jnci/djj158.
    1. Giuliano A.E., Ballman K.V., McCall L., Beitsch P.D., Brennan M.B., Kelemen P.R., Ollila D.W., Hansen N.M., Whitworth P.W., Blumencranz P.W., et al. Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017;318:918–926. doi: 10.1001/jama.2017.11470.
    1. Krag D.N., Anderson S.J., Julian T.B., Brown A.M., Harlow S.P., Costantino J.P., Ashikaga T., Weaver D.L., Mamounas E.P., Jalovec L.M., et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: Overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;11:927–933. doi: 10.1016/S1470-2045(10)70207-2.
    1. Veronesi U., Paganelli G., Viale G., Luini A., Zurrida S., Galimberti V., Intra M., Veronesi P., Maisonneuve P., Gatti G., et al. Sentinel-lymph-node biopsy as a staging procedure in breast cancer: Update of a randomised controlled study. Lancet Oncol. 2006;7:983–990. doi: 10.1016/S1470-2045(06)70947-0.
    1. Ahmed M., Purushotham A.D., Douek M. Novel techniques for sentinel lymph node biopsy in breast cancer: A systematic review. Lancet Oncol. 2014;15:e351–e362. doi: 10.1016/S1470-2045(13)70590-4.
    1. Bézu C., Coutant C., Salengro A., Daraï E., Rouzier R., Uzan S. Anaphylactic response to blue dye during sentinel lymph node biopsy. Surg. Oncol. 2011;20:e55–e59. doi: 10.1016/j.suronc.2010.10.002.
    1. Albo D., Wayne J.D., Hunt K.K., Rahlfs T.F., Singletary S.E., Ames F.C., Feig B.W., Ross M.I., Kuerer H.M. Anaphylactic reactions to isosulfan blue dye during sentinel lymph node biopsy for breast cancer. Am. J. Surg. 2001;182:393–398. doi: 10.1016/S0002-9610(01)00734-6.
    1. Teshome M., Wei C., Hunt K.K., Thompson A., Rodriguez K., Mittendorf E.A. Use of a Magnetic Tracer for Sentinel Lymph Node Detection in Early-Stage Breast Cancer Patients: A Meta-analysis. Ann. Surg. Oncol. 2016;23:1508–1514. doi: 10.1245/s10434-016-5135-1.
    1. Karakatsanis A., Christiansen P.M., Fischer L., Hedin C., Pistioli L., Sund M., Rasmussen N.R., Jörnsgård H., Tegnelius D., Eriksson S., et al. The Nordic SentiMag trial: A comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies. Breast Cancer Res Treat. 2016;157:281–294. doi: 10.1007/s10549-016-3809-9.
    1. Karakatsanis A., Daskalakis K., Stalberg P., Olofsson H., Andersson Y., Eriksson S., Bergkvist L., Wärnberg F. Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer. Br. J. Surg. 2017;104:1675–1685. doi: 10.1002/bjs.10606.
    1. Ghilli M., Carretta E., Di Filippo F., Battaglia C., Fustaino L., Galanou I., Di Filippo S., Rucci P., Fantini M.P., Roncella M. The superparamagnetic iron oxide tracer: A valid alternative in sentinel node biopsy for breast cancer treatment. Eur. J. Cancer Care. 2017;26 doi: 10.1111/ecc.12385.
    1. Rubio I.T., Diaz-Botero S., Esgueva A., Rodriguez R., Cortadellas T., Cordoba O., Espinosa-Bravo M. The superparamagnetic iron oxide is equivalent to the Tc99 radiotracer method for identifying the sentinel lymph node in breast cancer. Eur. J. Surg. Oncol. 2015;41:46–51. doi: 10.1016/j.ejso.2014.11.006.
    1. Warnberg F., Stigberg E., Obondo C., Olofsson H., Abdsaleh S., Warnberg M., Karakatsanis A. Long-Term Outcome After Retro-Areolar Versus Peri-Tumoral Injection of Superparamagnetic Iron Oxide Nanoparticles (SPIO) for Sentinel Lymph Node Detection in Breast Cancer Surgery. Ann. Surg. Oncol. 2019;26:1247–1253. doi: 10.1245/s10434-019-07239-5.
    1. Karakatsanis A., Olofsson H., Stalberg P., Bergkvist L., Abdsaleh S., Warnberg F. Simplifying Logistics and Avoiding the Unnecessary in Patients With Breast Cancer Undergoing Sentinel Node Biopsy. A Prospective Feasibility Trial of the Preoperative Injection of Super Paramagnetic Iron Oxide Nanoparticles. Scand. J. Surg. 2018;107:130–137. doi: 10.1177/1457496917738867.
    1. Alvarado M.D., Mittendorf E.A., Teshome M., Thompson A.M., Bold R.J., Gittleman M.A., Beitsch P.D., Blair S.L., Kivilaid K., Harmer Q.J., et al. SentimagIC: A Non-inferiority Trial Comparing Superparamagnetic Iron Oxide Versus Technetium-99m and Blue Dye in the Detection of Axillary Sentinel Nodes in Patients with Early-Stage Breast Cancer. Ann. Surg. Oncol. 2019;26:3510–3516. doi: 10.1245/s10434-019-07577-4.
    1. Rubio I.T., Rodriguez-Revuelto R., Espinosa-Bravo M., Siso C., Rivero J., Esgueva A. A randomized study comparing different doses of superparamagnetic iron oxide tracer for sentinel lymph node biopsy in breast cancer: The SUNRISE study. Eur. J. Surg. Oncol. 2020;46:2195–2201. doi: 10.1016/j.ejso.2020.06.018.
    1. Tudur Smith C., Marcucci M., Nolan S.J., Iorio A., Sudell M., Riley R., Rovers M.M., Williamson P.R. Individual participant data meta-analyses compared with meta-analyses based on aggregate data. Cochrane Database Syst. Rev. 2016;9:Mr000007. doi: 10.1002/14651858.MR000007.pub3.
    1. von Elm E., Altman D.G., Egger M., Pocock S.J., Gøtzsche P.C., Vandenbroucke J.P. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies. Lancet. 2007;370:1453–1457. doi: 10.1016/S0140-6736(07)61602-X.
    1. Stewart L.A., Clarke M., Rovers M., Riley R.D., Simmonds M., Stewart G., Tierney J.F. Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: The PRISMA-IPD Statement. JAMA. 2015;313:1657–1665. doi: 10.1001/jama.2015.3656.
    1. Karakatsanis A., Hersi A.F., Pistiolis L., Olofsson Bagge R., Lykoudis P.M., Eriksson S., Wärnberg F., Nagy G., Mohammed I., Sundqvist M., et al. Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study) Br. J. Surg. 2019;106:720–728. doi: 10.1002/bjs.11110.
    1. Krischer B., Forte S., Niemann T., Kubik-Huch R.A., Leo C. Feasibility of breast MRI after sentinel procedure for breast cancer with superparamagnetic tracers. Eur. J. Surg. Oncol. 2018;44:74–79. doi: 10.1016/j.ejso.2017.11.016.
    1. Karakatsanis A. Postoperative Breast Mri in Patients Undergoing Sentinel Node Biopsy Using Super Paramagnetic Iron Oxide Nanoparticles, 16 January 2018. [(accessed on 2 October 2020)]; Available online: .
    1. Yu J., Chen W., Chen S., Jia P., Su G., Li Y., Sun X. Design, Conduct, and Analysis of Surgical Randomized Controlled Trials: A Cross-sectional Survey. Ann. Surg. 2019;270:1065–1069. doi: 10.1097/SLA.0000000000002860.
    1. Riley R.D., Debray T.P.A., Fisher D., Hattle M., Marlin N., Hoogland J., Gueyffier F., Staessen J.A., Wang J., Moons K.G.M., et al. Individual participant data meta-analysis to examine interactions between treatment effect and participant-level covariates: Statistical recommendations for conduct and planning. Stat. Med. 2020;39:2115–2137. doi: 10.1002/sim.8516.
    1. Stewart L.A., Tierney J.F. To IPD or not to IPD? Advantages and disadvantages of systematic reviews using individual patient data. Eval. Health Prof. 2002;25:76–97. doi: 10.1177/0163278702025001006.
    1. Hua H., Burke D.L., Crowther M.J., Ensor J., Tudur Smith C., Riley R.D. One-stage individual participant data meta-analysis models: Estimation of treatment-covariate interactions must avoid ecological bias by separating out within-trial and across-trial information. Stat. Med. 2017;36:772–789. doi: 10.1002/sim.7171.
    1. The Use of Magtrace®/Sentimag® in Sentinel Node Biopsy for Malignant Melanoma The Magmen Study. [(accessed on 4 October 2020)]; Available online: .
    1. Winter A., Engels S., Goos P., Süykers M.C., Gudenkauf S., Henke R.P., Wawroschek F. Accuracy of Magnetometer-Guided Sentinel Lymphadenectomy after Intraprostatic Injection of Superparamagnetic Iron Oxide Nanoparticles in Prostate Cancer: The SentiMag Pro II Study. Cancers. 2019;12:32. doi: 10.3390/cancers12010032.
    1. Staník M., Macík D., Čapák I., Marečková N., Lžíčařová E., Doležel J. Sentinel lymph node dissection in prostate cancer using superparamagnetic particles of iron oxide: Early clinical experience. Int. Urol. Nephrol. 2018;50:1427–1433. doi: 10.1007/s11255-018-1903-0.
    1. Czarniecki M., Pesapane F., Wood B.J., Choyke P.L., Turkbey B. Ultra-small superparamagnetic iron oxide contrast agents for lymph node staging of high-risk prostate cancer. Transl. Androl. Urol. 2018;7(Suppl. 4):S453–S461. doi: 10.21037/tau.2018.05.15.
    1. Winter A., Kowald T., Engels S., Wawroschek F. Magnetic Resonance Sentinel Lymph Node Imaging and Magnetometer-Guided Intraoperative Detection in Penile Cancer, using Superparamagnetic Iron Oxide Nanoparticles: First Results. Urol. Int. 2020;104:177–180. doi: 10.1159/000502017.
    1. Murakami K., Kotani Y., Suzuki A., Takaya H., Nakai H., Matsuki M., Sato T., Mandai M., Matsumura M. Superparamagnetic iron oxide as a tracer for sentinel lymph node detection in uterine cancer: A pilot study. Sci. Rep. 2020;10:7945. doi: 10.1038/s41598-020-64926-0.

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