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

Andreas Karakatsanis, Peer Michael Christiansen, Lone Fischer, Christina Hedin, Lida Pistioli, Malin Sund, Nils Ryegaard Rasmussen, Hjørdis Jørnsgård, Daniel Tegnelius, Staffan Eriksson, Kosmas Daskalakis, Fredrik Wärnberg, Christos J Markopoulos, Leif Bergkvist, Andreas Karakatsanis, Peer Michael Christiansen, Lone Fischer, Christina Hedin, Lida Pistioli, Malin Sund, Nils Ryegaard Rasmussen, Hjørdis Jørnsgård, Daniel Tegnelius, Staffan Eriksson, Kosmas Daskalakis, Fredrik Wärnberg, Christos J Markopoulos, Leif Bergkvist

Abstract

The aim of the study is to compare the efficacy of SPIO as a tracer in sentinel node biopsy (SNB) in breast cancer with Tc and patent blue in a multicentre prospective study and perform a meta-analysis of all published studies. It also aims to follow skin discoloration after SPIO injection and describe when and how it resolves. Totally 206 patients with early breast cancer were recruited. Tc and patent blue were administered in standard fashion. Patients were injected with SPIO (Sienna+) preoperatively. SNB was performed and detection rates were recorded for both methods. Skin discoloration was followed and documented postoperatively. Data extraction and subsequent meta-analysis of all previous studies were also performed. SN detection rates were similar between standard technique succeeded and SPIO both per patient (97.1 vs. 97.6 %, p = 0.76) as well as per node (91.3 vs. 93.3 %, p = 0.34), something which was not affected by the presence of malignancy. Concordance rates were also consistently high (98.0 % per patient and 95.9 % per node). Discoloring was present in 35.5 % of patients postoperatively, almost exclusively in breast conservation. It fades slowly and is still detectable in 8.6 % of patients after 15 months. Meta-analysis depicted similar detection rates (p = 0.71) and concordance rates (p = 0.82) per patient. However, it seems that SPIO is characterized by higher nodal retrieval (p < 0.001). SPIO is an effective method for the detection of SN in patients with breast cancer. It is comparable to the standard technique and seems to simplify logistics. Potential skin discoloration is something of consideration in patients planned for breast conservation.

Keywords: Breast cancer; Sentinel node; Super paramagnetic iron oxide.

Figures

Fig. 1
Fig. 1
PRISMA flow chart for the conduct of the meta-analysis
Fig. 2
Fig. 2
Discoloration in the follow-up cohort; size and the colour of the spheres represent the medians of the discoloured surface in cm2 in the discoloured proportion of the cohort and the fading, respectively
Fig. 3
Fig. 3
Forest plot comparing detection rates per patient
Fig. 4
Fig. 4
Forest plot comparing detection rates per node
Fig. 5
Fig. 5
Forest plot comparing detection rates per patient in the presence of malignancy
Fig. 6
Fig. 6
Forest plot comparing detection rates per node in the presence of malignancy
Fig. 7
Fig. 7
Forest plot comparing concordance versus reverse concordance per patient
Fig. 8
Fig. 8
Forest plot comparing concordance versus reverse concordance per node
Fig. 9
Fig. 9
Forest plot comparing concordance versus reverse concordance per patient in the presence of malignancy
Fig. 10
Fig. 10
Forest plot comparing concordance versus reverse concordance per node in the presence of malignancy

References

    1. 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. doi: 10.1093/jnci/djj158.
    1. Ferrari A, Rovera F, Dionigi P, Limonta G, Marelli M, Besana Ciani I, Bianchi V, Vanoli C, Dionigi R. Sentinel lymph node biopsy as the new standard of care in the surgical treatment for breast cancer. Expert Rev Anticancer Ther. 2006;6:1503–1515. doi: 10.1586/14737140.6.10.1503.
    1. Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL, Benson AB, III, Bosserman LD, Burstein HJ, Cody H, III, Hayman J, Perkins CL, Podoloff DA, Giuliano AE, American Society of Clinical Oncology Clinical Practice Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2014;32:1365–1383. doi: 10.1200/JCO.2013.54.1177.
    1. Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, Denkert C, Eiermann W, Gnant M, Harris JR, Karn T, Liedtke C, Mauri D, Rouzier R, Ruckhaeberle E, Semiglazov V, Symmans WF, Tutt A, Pusztai L. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012;19:1508–1516. doi: 10.1245/s10434-011-2108-2.
    1. Straver ME, Meijnen P, van Tienhoven G, et al. Sentinel node identification rate and nodal involvement in the EORTC 10981-22023 AMAROS trial. Ann Surg Oncol. 2010;17:1854–1861. doi: 10.1245/s10434-010-0945-z.
    1. Ahmed M, Purushotham AD, 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. Masannat Y, Shenoy H, Speirs V, Hanby A, Horgan K. Properties and characteristics of the dyes injected to assist axillary sentinel node localization in breast surgery. Eur J Surg Oncol. 2006;32:381–384. doi: 10.1016/j.ejso.2006.01.010.
    1. White V, Harvey JR, Griffith CD, Youssef M, Carr M. Sentinel lymph node biopsy in early breast cancer surgery–working with the risks of vital blue dye to reap the benefits. Eur J Surg Oncol. 2011;37:101–108. doi: 10.1016/j.ejso.2010.12.007.
    1. Motomura K, Ishitobi M, Komoike Y, Koyama H, Noguchi A, Sumino H, Kumatani Y, Inaji H, Horinouchi T, Nakanishi K. SPIO-enhanced magnetic resonance imaging for the detection of metastases in sentinel nodes localized by computed tomography lymphography in patients with breast cancer. Ann Surg Oncol. 2011;18:3422–3429. doi: 10.1245/s10434-011-1710-7.
    1. Douek M, Klaase J, Monypenny I, Kothari A, Zechmeister K, Brown D, Wyld L, Drew P, Garmo H, Agbaje O, Pankhurst Q, Anninga B, Grootendorst M, Ten Haken B, Hall-Craggs MA, Purushotham A, Pinder S, SentiMAG Trialists Group Sentinel node biopsy using a magnetic tracer versus standard technique: the SentiMAG Multicentre Trial. Ann Surg Oncol. 2014;21:1237–1245. doi: 10.1245/s10434-013-3379-6.
    1. Thill M, Kurylcio A, Welter R, van Haasteren V, Grosse B, Berclaz G, Polkowski W, Hauser N. The Central-European SentiMag study: sentinel lymph node biopsy with superparamagnetic iron oxide (SPIO) vs. radioisotope. Breast. 2014;23:175–179. doi: 10.1016/j.breast.2014.01.004.
    1. Rubio IT, 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. Piñero-Madrona A, Torro-Richart JA, de Leon-Carrillo JM, de Castro-Parga G, Navarro-Cecilia J, Domingez-Cunchillos F, Roman-Santamarıa JM, Fuster-Diana C, Pardo-Garcıa R, on behalf of the “Grupo de Estudios Senologicos de la Sociedad Española de Patologia Mamaria (SESPM). (2015). Superparamagnetic iron oxide as a tracer for sentinel node biopsy in breast cancer: A comparative non-inferiority study. Eur J Surg Oncol 41: 991–997. doi: 10.1016/j.ejso.2015.04.017
    1. Ghilli M, Carretta E, Di Filippo F, Battaglia C, Fustaino L, Galanou I, Di Filippo S, Rucci P, Fantini MP, Roncella M. The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment. European Journal of Cancer Care. 2015
    1. Houpeau JL, Chauvet MP, Guillemin F, Bendavid-Athias C, Charitansky H, Kramar A, Giard S. Sentinel lymph node identification using superparamagnetic iron oxide particles versus radioisotope: the French Sentimag feasibility trial. J Surg Oncol. 2016
    1. Coufal O, Fait V, Lžičařová E, Chrenko V, Žaloudík J. SentiMag–the magnetic detection system of sentinel lymph nodes in breast cancer. Rozhl Chir. 2015;94:283–288.
    1. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological Index for Non-randomized Studies (MINORS): development and validation of a new instrument. ANJ J Surg. 2003;73:712–716.
    1. Shiozawa M, Lefor AT, Hozumi Y, Kurihara K, Sata N, Yasuda Y, Kusakabe M. Sentinel lymph node biopsy in patients with breast cancer using superparamagnetic iron oxide and a magnetometer. Breast Cancer. 2013;20:223–229. doi: 10.1007/s12282-011-0327-9.
    1. Pouw JJ, Ahmed M, Anninga B, Schuurman K, Pinder SE, Van Hemelrijck M, Pankhurst QA, Douek M, Ten Haken B. Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model. Int J Nanomedicine. 2015;10:1235–1243. doi: 10.2147/IJN.S76962.
    1. Rescigno J, Zampell JC, Axelrod D. Patterns of axillary surgical care for breast cancer in the era of sentinel lymph node biopsy. Ann Surg Oncol. 2009;16:687–696. doi: 10.1245/s10434-008-0195-5.
    1. Leong SP, Shen ZZ, Liu TJ, et al. Is breast cancer the same disease in Asian and Western countries? World J Surg. 2010;34:2308–2324. doi: 10.1007/s00268-010-0683-1.
    1. Ang CH, Tan MY, Teo C, Seah DW, Chen JC, Chan MY, Tan EY. Blue dye is sufficient for sentinel lymph node biopsy in breast cancer. Br J Surg. 2014;101:383–389. doi: 10.1002/bjs.9390.
    1. OʼReilly EA, Prichard RS, Al Azawi D, Aucharaz N, Kelly G, Evoy D, Geraghty J, Rothwell J, OʼDoherty A, Quinn C, Skehan SJ, McDermott EW. The value of isosulfan blue dye in addition to isotope scanning in the identification of the sentinel lymph node in breast cancer patients with a positive lymphoscintigraphy: a randomized controlled trial (ISRCTN98849733) Ann Surg. 2015;262:243–248. doi: 10.1097/SLA.0000000000001213.
    1. Cimmino VM, Brown AC, Szocik JF, Pass HA, Moline S, De SK, Domino EF. Allergic reactions to isosulfan blue during sentinel node biopsy–a common event. Surgery. 2001;130:439–442. doi: 10.1067/msy.2001.116407.
    1. Raut CP, Daley MD, Hunt KK, Akins J, Ross MI, Singletary SE, Marshall GD, Jr, Meric-Bernstam F, Babiera G, Feig BW, Ames FC, Kuerer HM. Anaphylactoid reactions to isosulfan blue dye during breast cancer lymphatic mapping in patients given preoperative prophylaxis. J Clin Oncol. 2004;22(3):567–568. doi: 10.1200/JCO.2004.99.276.
    1. Govaert GA, Oostenbroek RJ, Plaisier PW. Prolonged skin staining after intradermal use of patent blue in sentinel lymph node biopsy for breast cancer. Eur J Surg Oncol. 2005;31:373–375. doi: 10.1016/j.ejso.2004.12.009.
    1. Olliver JR, Wild CP, Sahay P, Dexter S, Hardie LJ. Chromoendoscopy with methylene blue and associated DNA damage in Barrett’s oesophagus. Lancet. 2003;362(9381):373–374. doi: 10.1016/S0140-6736(03)14026-3.
    1. Anninga B, Ahmed M, Van Hemelrijck M, Pouw J, Westbroek D, Pinder S, Ten Haken B, Pankhurst Q, Douek M. Magnetic sentinel lymph node biopsy and localization properties of a magnetic tracer in an in vivo porcine model. Breast Cancer Res Treat. 2013;141:33–42. doi: 10.1007/s10549-013-2657-0.
    1. Ahmed M, Anninga B, Pouw JJ, Vreeman S, Peek M, Van Hemelrijck M, Ten Haken B, Pankhurst Q, Douek M. Optimising magnetic sentinel lymph node biopsy in an in vivo porcine model. Nanomedicine. 2015;11:993–1002.
    1. Karakatsanis A, Olofsson H, Bergkvist L, Abdsaleh S, Sund M, Wärnberg F. How to avoid unnecessary SLNB in patients with DCIS. The Breast. 2015;24:S133–S134. doi: 10.1016/S0960-9776(15)70341-3.
    1. Sugie T, Sawada T, Tagaya N, Kinoshita T, Yamagami K, Suwa H, Ikeda T, Yoshimura K, Niimi M, Shimizu A, Toi M. 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;20:2213–2218. doi: 10.1245/s10434-013-2890-0.
    1. Aoyama K, Kamio T, Ohchi T, Nishizawa M, Kameoka S. Sentinel lymph node biopsy for breast cancer patients using fluorescence navigation with indocyanine green. World J Surg Oncol. 2011;9:157. doi: 10.1186/1477-7819-9-157.
    1. Shiozawa M, Kobayashi S, Sato Y, Maeshima H, Hozumi Y, Lefor AT, Kurihara K, Sata N, Yasuda Y. Magnetic resonance lymphography of sentinel lymph nodes in patients with breast cancer using superparamagnetic iron oxide: a feasibility study. Breast Cancer. 2014;21:394–401. doi: 10.1007/s12282-012-0401-y.
    1. Pouw JJ, Grootendorst MR, Bezooijen R, Klazen CA, De Bruin WI, Klaase JM, Hall-Craggs MA, Douek M, Ten Haken B. (2015) Pre-operative sentinel lymph node localization in breast cancer with superparamagnetic iron oxide MRI: the SentiMAG Multicentre Trial imaging subprotocol
    1. Teshome M, Wei C, Hunt KK, Thompson A, Rodriguez K, Mittendorf EA. Use of a magnetic tracer for sentinel lymph node detection in early-stage breast cancer patients: a meta-analysis. Ann Surg Oncol. 2016

Source: PubMed

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