Use of a Magnetic Tracer for Sentinel Lymph Node Detection in Early-Stage Breast Cancer Patients: A Meta-analysis

Abstract

Background

Sentinel lymph node (SLN) dissection involves lymphatic mapping and selective removal of clinically negative lymph nodes at highest risk for harboring metastases. Lymphatic mapping is most often performed using radioisotope with or without blue dye (standard tracers). Sienna+®, a superparamagnetic iron oxide that can be detected using the Sentimag® magnetometer, is an alternative mapping agent to identify SLNs that has been investigated in five clinical trials. This meta-analysis was performed to determine if Sienna+® is non-inferior for SLN detection when compared to standard tracers.

Methods

Five clinical trials comparing Sienna+® to a standard technique were identified, and data from these studies were used to determine the agreement by Kappa statistic between Sienna+® and standard tracers in identifying SLNs and malignant SLNs. The trials included 1683 SLNs identified in 804 patients. Data from the studies were imbalanced, therefore additional agreement indices were utilized to compare techniques. The estimated difference between the techniques was analyzed and a margin of ≤5 % was used to determine non-inferiority.

Results

Agreement between the Sienna+® and standard tracers was strong for SLN detection by patient [prevalence-adjusted bias-adjusted kappa (PABAK) 0.94, 95 % confidence interval (CI) 0.89–0.98], moderate to substantial for SLN detection by node (PABAK 0.68, 95 % CI 0.54–0.82), and strong for the detection of malignant SLNs by patient (PABAK 0.89, 95 % CI 0.84–0.95). Sienna+® demonstrated non-inferiority compared with standard tracers.

Conclusions

The Sienna+® mapping agent is non-inferior to the standard method for SLN detection in patients with clinically node-negative breast cancer.

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References

  1. 1.

    Krag DN, Anderson SJ, Julian TB, 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;11:927–33.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003;349:546–53.

    Article  PubMed  Google Scholar 

  3. 3.

    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  PubMed  Google Scholar 

  4. 4.

    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  PubMed  PubMed Central  Google Scholar 

  5. 5.

    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  PubMed  Google Scholar 

  6. 6.

    Mansel RE, Fallowfield L, Kissin M, 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.

    Article  PubMed  Google Scholar 

  7. 7.

    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  PubMed  Google Scholar 

  8. 8.

    Gill G; SNAC Trial Group of the Royal Australasian College of Surgeons (RACS) and NHMRC Clinical Trials Centre. Sentinel-lymph-node-based management or routine axillary clearance? One-year outcomes of sentinel node biopsy versus axillary clearance (SNAC): a randomized controlled surgical trial. Ann Surg Oncol. 2009;16:266–75.

    Article  PubMed  Google Scholar 

  9. 9.

    Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993;2:335–9.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Veronesi U, Paganelli G, Galimberti V, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet. 1997;349:1864–7.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Morrow M, Rademaker AW, Bethke KP, Talamonti MS, Dawes LG, Clauson J, et al. Learning sentinel node biopsy: results of a prospective randomized trial of two techniques. Surgery. 1999;126:714–22.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Cody HS 3rd, Fey J, Akhurst T, et al. Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 966 procedures. Ann Surg Oncol. 2001;8:13–9.

    Article  PubMed  Google Scholar 

  14. 14.

    Meyer-Rochow GY, Martin RC, Harman CR. Sentinel node biopsy in breast cancer: Validation study and comparison of blue dye alone with triple modality localization. ANZ J Surg. 2003;73:815–8.

    Article  PubMed  Google Scholar 

  15. 15.

    Hung WK, Chan CM, Ying M, Chong SF, Mak KL, Yip AWC. Randomized clinical trial comparing blue dye with combined dye and isotope for sentinel lymph node biopsy in breast cancer. Br J Surg. 2005;92:1494–7.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    VST-1001 (Dilute Fluorescein) for lymphatic mapping and localization of lymph nodes in patients with breast cancer. ClinicalTrials.gov Identifier NCT02294565. https://clinicaltrials.gov/ct2/show/NCT02294565?term=vestan&rank=1. Accessed 20 Jun 2015.

  17. 17.

    SentiMag® intraoperative comparison in breast cancer (SentiMagIC). ClinicalTrials.gov Identifier NCT02294565. https://clinicaltrials.gov/ct2/show/NCT02336737?term=sentimag&rank=1 Accessed 20 June 2015.

  18. 18.

    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  PubMed  Google Scholar 

  19. 19.

    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  PubMed  Google Scholar 

  20. 20.

    Rubio IT, Diaz-Botero S, Esgueva A, Rodriguez R, Cortadellas T, Cordoba O, 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.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    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.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Ghilli M, Carretta E, Di Filippo F, et al. The supramagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment. Eur J Cancer Care (Engl). 2015. doi:10.1111/ecc.12385

    Google Scholar 

  23. 23.

    Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.

    Article  Google Scholar 

  24. 24.

    Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.

    Article  Google Scholar 

  25. 25.

    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.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Yi M, Meric-Bernstam F, Ross MI, et al. How many sentinel lymph nodes are enough during sentinel lymph node dissection for breast cancer? Cancer. 2008;113:30–7.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Amr D, Broderick-Villa G, Haigh PI, Guenther JM, Difronzo LA. Adverse drug reactions during lymphatic mapping and sentinel lymph node biopsy for solid neoplasms. Am Surg. 2005;71:720–4.

    PubMed  Google Scholar 

  28. 28.

    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.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Raut CP, Hunt KK, Akins JS, et al. Incidence of anaphylactoid reactions to isosulfan blue dye during breast carcinoma lymphatic mapping in patients treated with preoperative prophylaxis: results of a surgical prospective clinical practice protocol. Cancer. 2005;104:692–9.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Wilke LG, McCall LM, Posther KE, et al. Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol. 2006;13:491–500.

    Article  PubMed  Google Scholar 

  31. 31.

    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  PubMed  Google Scholar 

  32. 32.

    Huizing E, Anninga B, Young P, Monypenny I, Hall-Craggs M, Douek M. Analysis of void artifacts in post-operative breast MRI due to residual SPIO after magnetic SLNB in SentiMAG Trial participants. Eur J Surg Oncol. 2015;41(6):S18.

    Article  Google Scholar 

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Disclosure

The University of Texas MD Anderson Cancer Center received an unrestricted educational grant from Endomagnetics, Inc. to support the statistical analyses for this study. Mediget Teshome, Caimiao Wei, Kelly K. Hunt, Alastair Thompson, Kelly Rodriguez, and Elizabeth A. Mittendorf have no additional conflicts of interest to report.

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Correspondence to Elizabeth A. Mittendorf MD, PhD.

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Teshome, M., Wei, C., Hunt, K.K. et al. Use of a Magnetic Tracer for Sentinel Lymph Node Detection in Early-Stage Breast Cancer Patients: A Meta-analysis. Ann Surg Oncol 23, 1508–1514 (2016). https://doi.org/10.1245/s10434-016-5135-1

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Keywords

  • Sentinel Lymph Node
  • Lymphatic Mapping
  • Positive Sentinel Lymph Node
  • Sentinel Lymph Node Dissection
  • Sentinel Lymph Node Detection