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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

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

A Correction to this article was published on 08 June 2020

This article has been updated

Abstract

Background

Sentinel lymph node biopsy (SLNB) is a highly accurate method for staging the axilla in early breast cancer. Superparamagnetic iron oxide mapping agents have been explored to overcome the disadvantages of the standard SLNB technique, which uses a radioisotope tracer with or without blue dye. One such agent, Sienna+, was shown to be non-inferior to the standard technique for SLNB in a number of studies. The SentimagIC trial was designed to establish the non-inferiority of a new formulation of this magnetic tracer, Magtrace (formerly SiennaXP).

Methods

Patients with clinically node-negative early-stage breast cancer were recruited from six centers in the US. Patients received radioisotope and isosulfan blue dye injections, followed by an intraoperative injection of magnetic tracer, prior to SLNB. The sentinel node identification rate was compared between the magnetic and standard techniques to evaluate non-inferiority and concordance.

Results

Data were collected for 146 procedures in 146 patients. The per patient detection rate was 99.3% (145/146) when using the magnetic tracer and 98.6% (144/146) when using the standard technique, while the nodal detection rate was 94.3% (348/369 nodes) when using the magnetic tracer and 93.5% (345/369) when using the standard technique (difference 0.8%, 95% binomial confidence interval lower bound − 2.1%). Of the 22 patients with positive sentinel lymph nodes (SLNs), 21 (95.4%) were detected by both the magnetic tracer and the standard technique. All malignant nodes detected by standard technique were also identified by the magnetic technique.

Conclusion

The magnetic technique is non-inferior to the standard technique of radioisotope and blue dye for axillary SLN detection in early-stage breast cancer. The magnetic technique is therefore a viable alternative.

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Change history

  • 08 June 2020

    In the original article the authors��� disclosures were incomplete.

References

  1. Ashikaga T, Krag DN, Land SR, et al. Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection. J Surg Oncol. 2010;102:111–8.

    Article  Google Scholar 

  2. Lucci A, McCall LM, Beitsch PD, et al. 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;25:3657–63.

    Article  Google Scholar 

  3. Mansel RE, Fallowfield L, Kissin M, et al. Randomized multi- center trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006;98:599–609.

    Article  Google Scholar 

  4. Del Bianco P, Zavagno G, Burelli P, 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 randomized clinical trial. Eur J Surg Oncol. 2008;34:508–13.

    Article  Google Scholar 

  5. Krag DN, Anderson SJ, Julian TB, et al. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph- node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol. 2007;8:881–8.

    Article  CAS  Google Scholar 

  6. Veronesi U, Viale G, Paganelli G, et al. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized control study. Ann Surg. 2010;251:595–600.

    Article  Google Scholar 

  7. Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23:7703–20.

    Article  Google Scholar 

  8. Peplow M. Blind medicine. Sci Am. 2017;316;68–71.

    Google Scholar 

  9. Albo D, Wayne JD, Hunt KK, et al. Anaphylactic reactions to isosulfan blue dye during sentinel lymph node biopsy for breast cancer. Am J Surg. 2001;182:393–8.

    Article  CAS  Google Scholar 

  10. Thevarajah S, Huston TL, Simmons RM. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer. Am J Surg. 2005;189:236–9.

    Article  Google Scholar 

  11. Masannat YA, Hanby A, Horgan K, et al. DNA damaging effects of the dyes used in sentinel node biopsy: possible implications for clinical practice. J Surg Res. 2009;154, 234–8.

    Article  CAS  Google Scholar 

  12. Rubio IT, Diaz-Botero S, Esgueva A, et al. The super paramagnetic 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.

    Article  CAS  Google Scholar 

  13. Douek M, Klasse J, Monypenny I, et al. Sentinel node biopsy using a magnetic tracer versus standard technique: the SentiMAG Multicentre Trial. Ann Surg Oncol. 2014;21:1237–45.

    Article  Google Scholar 

  14. Thill M, Kurkylcio A, Welter R, et al. The Central-European SentiMag study: sentinel lymph node biopsy with super paramagnetic iron oxide (SPIO) vs. radioisotope. Breast. 2014;23:175–9.

    Article  Google Scholar 

  15. Pinero-Madrona A, Torro-Richart JA, de Leon-Carrillo JM, et al. Superparamagnetic iron oxide as a tracer for sentinel node biopsy in breast cancer: a comparative non-inferiority study. Eur J Surg Oncol. 2015;41:991–7.

    Article  CAS  Google Scholar 

  16. Houpeau JL, Chauvet MP, Guillemin F, et al. Sentinel lymph node identification using superparamagnetic iron oxide particles versus radioisotope: the French SentiMag feasibility trial. J Surg Oncol. 2016;113:501–7.

    Article  CAS  Google Scholar 

  17. Ghilli M, Carretta E, Di Filippo F, et al. The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment. Eur J Cancer Care (Engl). 2017;26(4):e12385.

    Article  Google Scholar 

  18. Karakatsanis A, Christiansen PM, Fischer L, 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;157:281–94.

    Article  CAS  Google Scholar 

  19. Teshome M, Wei C, Hunt KK, et al. Use of a magnetic tracer for sentinel lymph node detection in early-stage breast cancer patients: a meta-analysis. Ann Surg Oncol. 2016;23(5):1508–14.

    Article  Google Scholar 

  20. Zada A, Peek MC, Ahmed M, et al. Meta-analysis of sentinel lymph node biopsy in breast cancer using the magnetic technique. Br J Surg. 2016;103(11):1409–19.

    Article  CAS  Google Scholar 

  21. Pouw JJ, Ahmed M, Anninga B, et al. Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model. Int J Nanomed. 2015;10:1235–43.

    Article  CAS  Google Scholar 

  22. Martin RC, Edwards MJ, Wong SL, et al. Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group. Surgery. 2000;128:139–144.

    Article  Google Scholar 

  23. Nam J, Kwon D, Non-inferiority tests for clustered matched-pair data. Stat Med. 2009;28:1668–79.

    Article  Google Scholar 

  24. Ahmed M, Purushotham AD, Douek M. Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review. Lancet Oncol. 2014;15:e351–62.

    Article  Google Scholar 

  25. Sugie T, Sawada T, Tagaya N, et al. Comparison of the indocyanine green fluorescence and blue dye methods in detection of sentinel lymph nodes in early-stage breast cancer. Ann Surg Oncol. 2013;20:2213–18.

    Article  Google Scholar 

  26. Aoyama K, Kamio T, Ohchi T, et al. Sentinel lymph node biopsy for breast cancer patients using fluorescence navigation with indocyanine green. World J Surg Oncol. 2011;9:157.

    Article  Google Scholar 

  27. Kehagias DT, Gouliamos AD, Smyrniotis V, et al. Diagnostic efficacy and safety of MRI of the liver with superparamagnetic iron oxide particles (SH U 555 A). J Magn Reson Imaging. 2001;14:595–601.

    Article  CAS  Google Scholar 

  28. Reimer P, Balzer T, Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast- enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol. 2003;13(6):1266–76.

    Article  Google Scholar 

  29. Winter A, Woenkhaus J, Wawroschek F, A novel method for intraoperative sentinel lymph node detection in prostate cancer patients using superparamagnetic iron oxide nanoparticles and a handheld magnetometer: the initial clinical experience. Ann Surg Oncol. 2014;21:4390–96.

    Article  Google Scholar 

  30. Anninga B, White SH, Moncrieff M, et al. Magnetic technique for sentinel lymph node biopsy in melanoma: the MELAMAG Trial. Ann Surg Oncol. 2016;23(6):2070–8.

    Article  Google Scholar 

  31. Wärnberg F, Stigberg E, Obondo C, et al. 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;26:1247–53.

    Article  Google Scholar 

  32. Krischer B, Forte S, Niemann T, et al. Feasibility of breast MRI after sentinel procedure for breast cancer with superparamagnetic tracers. Eur J Surg Oncol. 2018;44:74–9.

    Article  Google Scholar 

  33. Karakatsanis A, Obondo C, Abdsaleh S, et al. Optimisation of breast MRI compatibility after sentinel node biopsy with paramagnetic tracers. Eur J Surg Oncol. 2018;44:731–2.

    Article  Google Scholar 

  34. Karakatsanis A, Daskalakis K, Andersson Y, et al. superparamagnetic iron oxide (SPIO) as sole method for the detection of sentinel node (SN) in breast cancer. The MONOS study. Eur J Cancer. 2016;57:S60.

    Google Scholar 

  35. Karakatsanis A, Hersi A-F, Pistolis L, 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(6):720–8.

    Article  CAS  Google Scholar 

  36. Hunt KK, Euhus DM, Boughey JC, et al. Society of Surgical Oncology Breast Disease Working Group Statement on prophylactic (risk-reducing) mastectomy. Ann Surg Oncol. 2017;24(2):375–97.

    Article  Google Scholar 

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Acknowledgment

This clinical study was sponsored by Endomagnetics Inc. Clarice Scofield (Regulatory and Clinical Research Institute Inc.) provided clinical trial management, and Patrick Wang (University of California San Francisco) provided administrative support.

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Authors and Affiliations

  1. Department of Surgery, University of California San Francisco, San Francisco, CA, USA

    Michael D. Alvarado MD

  2. Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Elizabeth A. Mittendorf MD, Mediget Teshome MD, Alastair M. Thompson MD & Kelly K. Hunt MD

  3. Division of Surgical Oncology, Department of Surgery, UC Davis Medical Center, Sacramento, CA, USA

    Richard J. Bold MD

  4. Breastcare Specialists, Allentown, PA, USA

    Mark A. Gittleman MD

  5. Dallas Surgical Group, Dallas, TX, USA

    Peter D. Beitsch MD

  6. Department of Surgery, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA

    Sarah L. Blair MD

  7. Regulatory and Clinical Research Institute, Inc., Minneapolis, MN, USA

    Kaisa Kivilaid MS

  8. Endomagnetics Limited, Cambridge, UK

    Quentin J. Harmer PhD

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  1. Michael D. Alvarado MD
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  2. Elizabeth A. Mittendorf MD
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Correspondence to Michael D. Alvarado MD.

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Alvarado, M.D., Mittendorf, E.A., Teshome, M. 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 26, 3510–3516 (2019). https://doi.org/10.1245/s10434-019-07577-4

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