Original Research
Women's Imaging
June 5, 2019

Feasibility of Magnetic Seeds for Preoperative Localization of Axillary Lymph Nodes in Breast Cancer Treatment

Abstract

OBJECTIVE. The objective of this study was to evaluate the feasibility of using a magnetic seed system for preoperative localization of axillary lymph nodes in patients with breast cancer.
MATERIALS AND METHODS. We performed a retrospective analysis that included patients with breast cancer who underwent preoperative magnetic seed localization of axillary lymph nodes at our institution between January 1, 2017, and January 1, 2019. Magseed (Endomag) is a nonradioactive inducible magnetic seed that is induced to become a magnet when under the influence of its detector in the operating room. Clinical history, prior axillary sampling and clip placement, and procedure details and surgical outcomes were determined from a search of our PACS and electronic medical records.
RESULTS. Thirty-five patients (34 women and one man) composed our study cohort. The mean patient age was 56 years (range, 32–78 years). One patient underwent two separate consecutive localizations for two separate operations, and another patient had bilateral lesions, for a total of 37 axillary lymph node localizations. One case of seed misplacement occurred during the ultrasound-guided localization procedure, resulting in immediate placement of a second seed, for a total of 38 Magseeds placed. All seeds were placed under ultrasound guidance. The mean number of days from seed placement to surgery was 5 days (range, 0–31 days). Thirty-seven of 38 Magseeds (97%) were documented to be successfully retrieved in the operating room.
CONCLUSION. Magseed localization appears to be a safe, nonradioactive way to accurately localize axillary lymph nodes preoperatively.
Ipsilateral axillary lymph nodes are often the first site of spread in invasive breast cancer. Nodal status is an important prognostic indicator in patients with breast cancer and is used to guide local, regional, and systemic treatments [1]. Patients presenting with suspicious lymph nodes on physical examination or imaging often undergo ultrasound-guided sampling to document nodal metastatic disease. Historically, the treatment of metastatic axillary lymph nodes has involved axillary lymph node dissection in which all level I and level II axillary nodes are removed. Axillary lymph node dissection is associated with risks of substantial patient morbidity related to complications such as lymphedema and paresthesias [24].
Patients with nodal disease may undergo neoadjuvant chemotherapy (NAC) to reduce disease burden preoperatively. Such patients traditionally underwent axillary lymph node dissection because of the high false-negative rate of sentinel lymph node dissection after NAC. In the American College of Surgeons Oncology Group (ACOSOG) Z1071 trial, patients with node-positive disease underwent NAC followed by both sentinel and axillary lymph node dissection to determine the false-negative rate of sentinel lymph node dissection in this setting. A false-negative rate of 12.6% was seen with the use of standard sentinel lymph node dissection [5]. This high false-negative rate may in part relate to the fact that the biopsy-proven meta-static axillary lymph node is not always the sentinel node. Of interest, in a subset of 141 patients in the ACOSOG Z1071 trial, a clip was placed into the biopsy-proven metastatic node before initiation of systemic therapy. In this subset, if the clipped node was in the operative specimen, the false-negative rate was 6.8%, compared with 19.0% if it was not in the specimen [6]. Clip placement and preoperative localization of biopsy-proven meta-static axillary nodes are becoming part of the standard approach to axillary management in the setting of neoadjuvant therapy, as was reflected in the recent National Comprehensive Cancer Center guidelines [7].
Various techniques for localizing axillary nodes have been reported, including wire placement, use of radioactive seeds, and infrared or electromagnetic localization. At our institution, localization is now routinely performed using Magseed (Endomag). Mag-seed is a nonradioactive localization system consisting of a proprietary stainless steel magnetic seed that is induced to become a magnet under the influence of its detector in the operating room. This technique was approved for breast lesion localization by the U.S Food and Drug Administration in 2016.
We sought to evaluate outcomes and the feasibility of using Magseed for axillary node localization.

Materials and Methods

Study and Subjects

This HIPAA-compliant study was approved by an institutional review board. We performed a retrospective analysis of 35 patients with breast cancer who underwent preoperative magnetic seed localization of axillary lymph nodes at our institution between January 1, 2017, and January 1, 2019. All seeds were placed under ultrasound guidance in the breast imaging department by one of seven radiologists who subspecialized in breast imaging and had 1 year to 28 years of experience. Seeds were subsequently retrieved in the operating room by a surgeon who subspecialized in breast surgery and had 5–28 years of experience.

Magseed System

The Magseed system has been described in previous research [8]. In brief, a 5 × 1 mm proprietary stainless steel seed is preloaded into a 12- or 20-cm 18-gauge deployment needle. Seed placement performed under ultrasound guidance is similar to sonographically guided clip placement. The seed is localized in the operating room using the Sentimag (Endomag) magnetometer. Sentimag creates an alternating magnetic field that transiently magnetizes the seed. The surgeon uses a probe to scan the axilla for the seed, and the detector provides real-time audible and visual numeric feedback, allowing the surgeon to determine the location of the seed. After removal, the Sentimag probe is used to verify the signal (and thus the seed) in the specimen. In addition, a specimen radiograph is obtained in the operating room to ensure visualization of the seed.

Data Collection and Analyses

We reviewed electronic medical records to collect information pertaining to clinical history, prior axillary sampling and clip placement, and procedure details, including successful seed placement, complications (if any), and whether a postlocalization mammogram was obtained. Surgical details such as intraoperative imaging, successful retrieval of magnetic seed and target, and surgical complications (if any) were determined from the electronic medical records.
Sample mean values and ranges were calculated.

Results

Thirty-five patients (34 women and one man) composed our final study cohort. The mean patient age was 56 years (range, 32–78 years). One patient underwent two separate consecutive localizations for two separate operations, and another patient had bilateral lesions, for a total of 37 axillary lymph node localizations. In one patient, the first seed was misplaced from the target, so a second seed was immediately placed while the patient was still in the breast imaging department, for a total of 38 Magseeds placed.
Thirty-five of the 37 nodes (95%) were biopsy-proven metastatic carcinoma before preoperative localization. The remaining two nodes (5%) underwent localization after needle biopsy findings were negative, because of concern for undersampling. Clips were placed in 32 of 37 nodes (86%) at the time of sampling. Five of 37 nodes (14%) had no clip placement.
Other than the single case of seed misplacement that occurred at the time of deployment, no documented complications occurred during Magseed placement. For 32 of 37 nodes (86%), mammograms were obtained after Magseed placement. The Mag-seed was visualized in the axillary lymph node on 31 of 32 of these mammograms (97%), and for one patient (3%) with an implant, the Magseed and axillary lymph node were not visualized in the FOV.
The mean number of days from seed placement to surgery was 5 days (range, 0–31 days). Thirty of 35 of patients (86%) underwent NAC or endocrine therapy before localization.
Successful retrieval was documented for 37 of 38 Magseeds (97%), either on a specimen radiograph (n = 36) or by surgeon confirmation of excision in which the detector in the operating room was used to confirm the presence of Magseed in specimen (n = 1).
In a single patient (3%), the Magseed was not definitively detected in the operating room, on a specimen radiograph, or by pathologic analysis. However, the targeted node and clip were documented to be retrieved on a specimen radiograph and by pathologic analysis. In addition, the surgeon scanned the axilla with the detector, and no signal was noted in the axilla after dedicated searching. On postoperative MRI, no significant artifact was seen in the axilla, as would be expected with a residual seed in place, further supporting its removal at surgery. Thus, it is believed the Magseed was lost in the operating room, possibly during local suction.
In a single patient (3%), the Magseed was retrieved, but the biopsy clip demarcating the target node was not seen in the specimen. Final pathologic analysis of this patient who had undergone NAC revealed a pathologic complete response, with no residual disease seen in the breast or in the two retrieved nodes. The patient has not undergone follow-up imaging and is believed to be disease free on the basis of the clinical findings.
No other complications related to retrieval of the Magseed and target node in the operating room were observed.

Discussion

To our knowledge, this is the first reported study of the use of Magseed for preoperative localization of axillary lymph nodes. On the basis of our initial experience, Magseed appears to be a safe, accurate, nonradioactive method for accurately localizing axillary lymph nodes preoperatively, with 97% of Magseeds and 97% of target nodes successfully removed at surgery. These findings are of substantial clinical value as precision axillary surgery becomes the norm. Successful removal of the biopsy-proven metastatic node at the time of sentinel lymph node surgery after neoadjuvant chemotherapy reduces the false-negative rate of sentinel lymph node surgery [6]. This removal is made more feasible with the use of Magseed localization, as our study shows.
Alternative localization methods exist. For the past several decades, wires have been the standard method used for preoperative localization of lesions in the breast [9]. However, several inherent limitations of the wire localization method exist, including the need for placement to be performed on the same day as surgery, the surgical approach being limited, and the possibility of the wire becoming dislodged or transected. With regard to the axilla in particular, close proximity to major vessels adds a further safety concern, and at some institutions, ours included, wire localization of axillary lesions is not performed. Although some institutions do perform wire localization of axillary nodes, data suggest that this method is challenging. One study examining ultrasound-guided wire localization of biopsy-proven axillary metastatic nodes after primary systemic therapy found that the selective surgical removal of a wire-localized targeted axillary lymph node was possible in only 17 of 24 patients (71%), despite all surgeons having experience in breast and axillary surgery. The explanations given for this included the wire possibly becoming displaced secondary to patient movement or surgeon manipulation in the soft fatty axillary tissue [10]. This explanation is in contrast to our results, with a 97% success rate noted for seed localization in the axilla, as well as in contrast to a prior report on axillary localization via radioactive 125I seeds, which was successful in 97–100% of cases [11, 12]. Radioactive seed localization, however, requires radioisotope administration and therefore intense regulations and multi-departmental coordination.
Magseed has only recently been successfully used in breast lesion localization. Both Price et al. [8] and Lamb et al. [13] documented a 100% successful retrieval rate in their initial experience of breast lesion localization with Magseed. All studies evaluating the Magseed localization system for breast targets have found Magseed to be a feasible, safe, and effective localization method [8, 13, 14]. Magseed successfully decouples the radiology department and localization procedure from the operating room schedule.
Challenges associated with Magseed use include cost, MRI artifact, limitations regarding the depth of insertion, and a minimum distance of 2 cm between seeds. Newer localization technologies, including Mag-seed, are known to be more expensive than wire localization. However, the decoupling of localization from the operating room schedule may increase operating room efficiency and overcome the greater expense of the seeds. For the detector probe to be able to detect the seed percutaneously, the recommended maximum depth for placement of Magseeds is 4 cm. However, per our surgeons, the depth of the axillary node has not been an issue. A standard incision is made for axillary lesions, and once within the axilla, the probe has consistently identified all axillary seeds regardless of depth. With regard to the minimal distance between seeds, if more than one seed is placed, the vendor recommends that Magseeds be placed no closer than 2 cm from each other to ensure sufficient signal detection from each individual seed. This is rarely an issue in the axilla, where only a single seed is typically placed. In our complicated case in which a second seed was needed, there was no difficulty with retrieval of either seed. Similarly, our surgeons have not had issues with seeds placed in close proximity, whether they were placed for two lesions in the breast or for a high upper outer quadrant breast lesion and nearby axillary lesion.
Three patients in our study had complications. These complications included a Magseed misplaced during the localization procedure, a Magseed possibly lost in the operating room, and an instance in which the targeted node with clip was not retrieved with the seed.
Magseed misplacement occurred in a 39-year-old woman with multifocal left breast carcinoma and axillary metastases who had undergone NAC. Immediately after ultrasound-guided Magseed localization, a postprocedural mammogram was obtained, and the seed was noted to be 4 cm inferior to the clipped node, which showed that the wrong lymph node had been localized. Therefore, the patient underwent ultrasound again, the correct clipped node was identified, and a second Magseed was immediately placed. Subsequently performed mammography showed the second seed to be located at the site of the clipped node. The targeted node with clip and both Magseeds were successfully retrieved in the operating room.
A single patient had a possibly lost Mag-seed. Despite the seed not being definitively seen on a specimen radiograph or on pathologic analysis, the surgeon was confident that the seed was removed and thought that it likely was dropped or suctioned out during surgery. No signal was seen in the axilla when it was scanned by the probe, as would be expected if a seed remained in situ. According to our surgeons, when a seed is present in the axilla, the detector gives off a solid and constant signal. Also, the target was successfully retrieved from this patient, and no specific management of the lost Magseed was required. This is substantially different from the protocol for a lost radioactive seed, which would require notification of an emergency response team and a multidepartmental effort [15]. The potential negative consequences of nonretrieval of a Magseed include potential target node nonretrieval (which was not the scenario for this patient) and substantial artifact obscuring underlying tissue on future MRI.
In the single patient who had undergone NAC and in whom the targeted clipped node was not retrieved with the Magseed, two nodes and the Magseed were retrieved. A possible explanation for this was that the seed was placed into a node without a clip because the clip was not definitively seen on any of the prelocalization images. Another potential explanation is that the biopsy clip was dropped or suctioned out in the operating room. This patient underwent no further imaging follow-up; however, the patient was believed to be disease free on the basis of clinical findings.
Eighty-six percent of the patients in our study underwent NAC or hormonal treatment before axillary node localization. The potential difficulty in identifying the correct axillary node after shrinkage during NAC is a concern. In our practice, this has not been a substantial problem. Placing a clip in the node at the time of biopsy, particularly a clip that is easily identifiable on ultrasound, such as a HydroMARK clip (Devicor Medical Products), is also helpful in identifying the previously biopsied node, even if there is treatment response. In all patients undergoing NAC in the current study, even in the setting of treatment response, the axillary node was identifiable on ultrasound and was successfully localized with ultrasound-guided Mag-seed placement (Fig. 1). However, if the clip or node is not visualized on ultrasound, as may occur in patients undergoing NAC who have a treatment response, and localization is requested, other localization methods, such as CT-, MRI-, and tomosynthesis-guided methods, may be feasible [16]. A recent study evaluating tomosynthesis-guided localizations of axillary nodes showed promising results. Ten axillary lesions (with biopsy clips in sonographically normalized axillary nodes after NAC) were all successfully localized using radioactive seeds under tomosynthesis guidance [17]. One potential downside to tomosynthesis-guided localization is seed displacement caused by the accordion affect, which is not an issue for ultrasound-guided localization.
Fig. 1A —59-year-old woman with recurrent right axillary adenocarcinoma.
A, Ultrasound image shows status of abnormal axillary lymph node with clip (HydroMARK clip, Devicor Medical Products) (arrow) after axillary fine-needle aspiration yielding adenocarcinoma.
Fig. 1B —59-year-old woman with recurrent right axillary adenocarcinoma.
B, Ultrasound images obtained after image shown in A reveal decreased size of abnormal axillary lymph node with clip in place (arrow, B) after patient underwent neoadjuvant chemotherapy; localization of clipped axillary node (arrow, C) with nonradioactive inducible magnetic seed (Magseed, Endomag); and Magseed (arrow, D) in clipped node.
Fig. 1C —59-year-old woman with recurrent right axillary adenocarcinoma.
C, Ultrasound images obtained after image shown in A reveal decreased size of abnormal axillary lymph node with clip in place (arrow, B) after patient underwent neoadjuvant chemotherapy; localization of clipped axillary node (arrow, C) with nonradioactive inducible magnetic seed (Magseed, Endomag); and Magseed (arrow, D) in clipped node.
Fig. 1D —59-year-old woman with recurrent right axillary adenocarcinoma.
D, Ultrasound images obtained after image shown in A reveal decreased size of abnormal axillary lymph node with clip in place (arrow, B) after patient underwent neoadjuvant chemotherapy; localization of clipped axillary node (arrow, C) with nonradioactive inducible magnetic seed (Magseed, Endomag); and Magseed (arrow, D) in clipped node.
Fig. 1E —59-year-old woman with recurrent right axillary adenocarcinoma.
E, Radiograph of specimen shows Magseed in node with HydroMARK clip as well as additional node removed.
In 86% of cases, a mammogram was obtained after seed placement. At our institution, mammographic evaluation of an axillary procedure is performed at the discretion of the attending radiologist on a case-by-case basis. A postprocedure mammogram confirms seed deployment and accurate placement and can be helpful to the surgeon in the operating room. A mammogram obtained after seed placement would also be needed when coincident breast lesion localization is performed (Fig. 2) or when there is concern about nondeployment or inaccurate placement of the seed. Postlocalization mammography can be performed using a mediolateral oblique, axillary tail, or axillary view or using tomosynthesis. At the discretion of the attending radiologist at our institution, for cases in which the target node, biopsy clip, and well-positioned Magseed are definitively visualized and documented on ultrasound, mammography may be deferred.
Fig. 2A —69-year-old woman with history of right lumpectomy with right breast recurrence with biopsy-proven metastatic disease in right axilla.
A, Ultrasound images show ultrasound-guided localization of right axillary node (arrow, A) and right breast invasive ductal carcinoma (B) with nonradioactive inducible magnetic seed (Magseed, Endomag).
Fig. 2B —69-year-old woman with history of right lumpectomy with right breast recurrence with biopsy-proven metastatic disease in right axilla.
B, Ultrasound images show ultrasound-guided localization of right axillary node (arrow, A) and right breast invasive ductal carcinoma (B) with nonradioactive inducible magnetic seed (Magseed, Endomag).
Fig. 2C —69-year-old woman with history of right lumpectomy with right breast recurrence with biopsy-proven metastatic disease in right axilla.
C, Right mediolateral oblique mammogram obtained after ultrasound-guided Magseed localization shows Magseed in axillary node (thin arrow) and Magseed in clipped breast mass (thick arrow).
The present study is limited by the small number of Magseed localizations of axillary lymph nodes. It is also limited by its retrospective nature. In addition, it was performed at a single academic institution where all five breast surgeons who performed localized axillary surgeries had preexisting experience with Magseed technology for breast lesion localization. However, all breast radiologists and breast surgeons at our institution have quickly and successfully learned the use of this technology, suggesting its generalizability.

Conclusion

In conclusion, our initial experience with preoperative Magseed localization of the axillary lymph nodes suggests that this is a feasible, safe, nonradioactive technique for the management of nodal metastases in breast cancer. Future research should include larger studies to further validate these initial findings.

References

1.
Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner MJD. SEER survival monograph: cancer survival among adults—U.S. SEER Program 1988-2001, patient and tumor characteristics. NIH Pub. No 07-6215. Bethesda, MD: National Cancer Institute, 2007
2.
Lucci A, McCall LM, Beitsch PD, et al.; American College of Surgeons Oncology Group. 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
3.
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
4.
Giuliano AE, Ballman KV, McCall L, 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
5.
Boughey JC, Suman VJ, Mittendorf EA, et al.; Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 2013; 310:1455–1461
6.
Boughey JC, Ballman KV, Le-Petross HT, et al. Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (Alliance). Ann Surg 2016; 263:802–807
7.
National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology, breast cancer, version 3.2017. Plymouth Meeting, PA: NCCN, 2017
8.
Price ER, Khoury AL, Esserman LJ, Joe BN, Alvarado MD. Initial clinical experience with an inducible magnetic seed system for preoperative breast lesion localization. AJR 2018; 210:913–917
9.
Kopans DB, DeLuca S. A modified needle-hook-wire technique to simplify preoperative localization of occult breast lesions. Radiology 1980; 134:781
10.
Hartmann S, Reimer T, Gerber B, Stubert J, Stengel B, Stachs A. Wire localization of clip-marked axillary lymph nodes in breast cancer patients treated with primary systemic therapy. Eur J Surg Oncol 2018; 44:1307–1311
11.
Donker M, Straver ME, Wesseling J, et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg 2015; 261:378–382
12.
Straver ME, Loo CE, Alderliesten T, Rutgers EJ, Vrancken Peeters MT. Marking the axilla with radioactive iodine seeds (MARI procedure) may reduce the need for axillary dissection after neoadjuvant chemotherapy for breast cancer. Br J Surg 2010; 97:1226–1231
13.
Lamb LR, Bahl M, Specht MC, D'Alessandro HA, Lehman CD. Evaluation of a nonradioactive magnetic marker wireless localization program. AJR 2018; 211:940–945
14.
Harvey JR, Lim Y, Murphy J, et al. Safety and feasibility of breast lesion localization using magnetic seeds (Magseed): a multi-centre, open-label cohort study. Breast Cancer Res Treat 2018; 169:531–536
15.
Goudreau SH, Joseph JP, Seiler SJ. Preoperative radioactive seed localization for nonpalpable breast lesions: technique, pitfalls, and solutions. RadioGraphics 2015; 35:1319–1334
16.
Samreen N, Lee CU, Bhatt AA. Nonconventional options for tumor localization in breast and axillary lymph nodes: a pictorial how-to. J Clin Imaging Sci 2018; 8:54
17.
Choudhery S, Simmons C, Harper L, Lee CU. Tomosynthesis-guided needle localization of breast and axillary lesions: our initial experience. AJR 2019; 212:943–946

Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 953 - 957
PubMed: 31166765

History

Submitted: February 28, 2019
Accepted: April 9, 2019
Version of record online: June 5, 2019

Keywords

  1. axilla
  2. breast cancer
  3. localization
  4. Magseed
  5. ultrasound

Authors

Affiliations

Heather I. Greenwood
Department of Radiology and Biomedical Imaging, University of California San Francisco, 1600 Divisadero St, Rm C-250, San Francisco, CA 95115.
Jasmine M. Wong
Department of Surgery, University of California San Francisco, San Francisco, CA.
Rita A. Mukhtar
Department of Surgery, University of California San Francisco, San Francisco, CA.
Michael D. Alvarado
Department of Surgery, University of California San Francisco, San Francisco, CA.
Elissa R. Price
Department of Radiology and Biomedical Imaging, University of California San Francisco, 1600 Divisadero St, Rm C-250, San Francisco, CA 95115.

Notes

Address correspondence to H. I. Greenwood ([email protected]).

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