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Original Study

Effectiveness and Safety of Magseed Localization for Excision of Breast Lesions

A Prospective, Phase IV Trial

Singh, Puneet MD*; Scoggins, Marion E. MD; Sahin, Aysegul A. MD; Hwang, Rosa F. MD*; Kuerer, Henry M. MD, PhD*; Caudle, Abigail S. MD*; Mittendorf, Elizabeth A. MD, PhD*; Thompson, Alastair M. MBChB, MD*; Bedrosian, Isabelle MD*; Teshome, Mediget MD*; DeSnyder, Sarah M. MD*; Meric-Bernstam, Funda MD*,§; Hunt, Kelly K. MD*

Author Information
doi: 10.1097/AS9.0000000000000008
  • Open

Abstract

INTRODUCTION

Wire localization has been routinely used for preoperative localization of nonpalpable lesions requiring surgical excision. Despite its widespread use and lower cost, disadvantages of wires include patient discomfort, wire migration, displacement or transection, and suboptimal incision location affecting cosmesis.1–3 Furthermore, wires must be placed the day of surgery resulting in scheduling challenges.1–3 Due to these disadvantages, radioactive iodine (125I) seeds were developed as an alternative localization device. An additional advantage is that the same intraoperative gamma probe used for the sentinel lymph node biopsy can be used to detect the radioactive seed.2 A Cochrane review of 2 randomized controlled trials comparing radioactive seed localization versus wire localization demonstrated comparable results with regard to successful excision, and neither method was found to be superior.4 However, the major drawback of radioactive seeds is the regulatory issues associated with the radioactivity,1–3 and therefore, this localization method has not replaced wire localization at many institutions. Over the last few years, several new localization devices have been introduced including the SAVI SCOUT (Cianna Medical), which uses infrared light and radar technology and was approved by the US Food and Drug Administration (FDA) in 2014,2 and Magseed (Endomagnetics, Inc.) which received FDA approval in 2016.5 The Magseed is a metallic magnetic marker measuring 5 × 0.9 mm that is deployed using an 18 gauge needle and detected with the Sentimag (Endomagnetics, Inc.) handheld magnetometer attached to a base unit (Fig. 1).

FIGURE 1.
FIGURE 1.:
Sentimag localization system. A, Magseed metallic magnetic marker. B, Sentimag handheld magnetometer probe connected to the base unit.

The first report of Magseed utilization was a single institution feasibility study with 64 patients who underwent placement of 73 Magseeds by Price et al.5 There was accurate localization of target lesions in the vast majority of cases, and all Magseeds were surgically retrieved. The authors concluded that this device was effective in localization of nonpalpable breast lesions.5 Another safety and feasibility trial of 28 patients conducted in the United Kingdom demonstrated no migration of the Magseed, 100% detection rate intraoperatively, and no complications providing the basis for the CE mark (European medical device safety mark).6 Much of these early data have allowed for gradual adoption of Magseed throughout the United States and Europe. However, a prospective, postmarketing trial to evaluate device safety and effectiveness in a larger cohort was important, and to our knowledge, this is the first study designed to assess these objectives.

METHODS

Study Design

This was a prospective, open-label, single-arm phase IV study conducted at a single institution after receiving institutional review board approval (NCT03020888). Between January 2017 to February 2018, patients 18 years or older with nonpalpable breast lesions requiring excision, either segmental mastectomy or excisional biopsy, were recruited through the University of Texas MD Anderson Cancer Center Department of Breast Surgical Oncology and written informed consent was obtained before enrollment. Exclusion criteria included pregnant or lactating patients, patients with a pacemaker or other implantable device in the chest wall, or patients with current active infection (per investigator discretion). Baseline demographic information including age, gender, height, and weight and clinical history including breast history and density, menopausal status, tumor or lesion size, stage, method of detection, and neoadjuvant chemotherapy status were collected.

Localization and Surgery

Dedicated breast radiologists placed 1 to 3 Magseeds, as clinically appropriate, under mammographic or ultrasound guidance within 30 days of surgery. If multiple Magseeds were placed, the distance between markers was required to be 20 mm or greater to detect distinct signals from each marker. Postprocedure mammogram was performed to document placement of the Magseed and location relative to the biopsy clip and/or target lesion. Data collected during the radiographic placement of the Magseed included localization method, location and depth of the lesion, duration of procedure, number of markers placed, and accuracy of placement. The radiologist was surveyed on ease of placement on a 3-point Likert scale ranging from very easy to difficult.

There were 10 surgeons in the breast surgery program who participated in the trial and whose practice included wire localization and radioactive seed localization. During surgery, the surgeon first evaluated the transcutaneous signal with the Sentimag probe and then began the operation by making an incision. Using the Sentimag probe as a guide, the target breast tissue was excised and sent for immediate evaluation with a specimen radiograph. Intraoperative specimen radiograph was utilized to confirm the presence of the Magseed. Time and duration of segmental mastectomy or surgical excisional biopsy were recorded. At the completion of the operation, the surgeon was surveyed on ease of transcutaneous localization and intraoperative localization (after incision) using a 4-point Likert scale ranging from very easy to difficult. The pathologist was also surveyed on the ease of Magseed identification and retrieval in the specimen using the same 4-point Likert scale.

Postoperatively, patients underwent an evaluation within 8 weeks of surgery to assess for adverse events and pathologic outcomes. Pathologic outcomes included final histopathology, margin status, and need for second operation and rationale. Margin status was determined for malignant lesions based on the Society of Surgical Oncology–American Society of Radiation Oncology–American Society of Clinical Oncology-published guidelines which is our standard institutional practice.7,8 Patients completed study participation once the postoperative visit was completed.

Outcomes

The primary outcome of the study was Magseed retrieval rate which was calculated as the percentage of patients in whom the initial excised specimen contained the Magseed and target lesion divided by the total number of patients. The study was powered to provide an exact 95% confidence interval for the primary outcome. Secondary outcomes included rates of device-related adverse events, accuracy and duration of radiographic localization, duration of breast surgical procedure, positive margin and re-excision rates, and clinician surveys of ease of use of the Magseed. Device-related adverse events were defined as untoward medical occurrences, unintended disease, or injury caused by or related to the Magseed directly as determined by the investigators.

Summary statistics were performed analyzing the data for the primary and secondary outcomes. Fisher exact test was performed to assess univariable associations with positive margins followed by multivariable analysis using SAS software (version 9.4; SAS Institute Inc., Cary, NC).

RESULTS

There were 120 patients enrolled in the trial. Thirteen were excluded due to patient withdrawal (n = 6), investigator withdrawal (n = 4), and insurance denial (n = 3; Fig. 2). Cases of investigator withdrawal included a patient who was unable to remain still for Magseed placement, a patient discovered to have a spinal neurostimulator, a patient who was unable to obtain insurance clearance in time for seed placement, and a patient who elected to receive neoadjuvant chemotherapy near the end of the trial accrual period. The final cohort included 107 patients who underwent Magseed-localized breast conserving surgery with a total of 124 Magseeds placed; 93 patients had 1 Magseed placed, 11 patients had 2 Magseeds placed, and 3 patients had 3 Magseeds placed. No patients were lost to follow-up. There were 2 protocol deviations including 1 patient who elected to complete the postoperative evaluation outside the study center and 1 patient who had 2 seeds placed 17 mm apart rather than the protocol-defined 20 mm apart. Both patients were included in the analysis. The mean age of the cohort was 61 years (29–87). Median body mass index was 28.2 (19.0–49.1), and 61% had category C breast density (heterogeneously dense; Table 1).

Table 1.
Table 1.:
Summary Characteristics of the Cohort (n = 107)
FIGURE 2.
FIGURE 2.:
CONSORT diagram of trial participants.

Radiographic breast lesions localized with the Magseed included masses (63%), calcifications (24%), architectural distortion (7%), and other lesions such as asymmetry (6%; Fig. 3). The median lesion size was 13 mm (0–60). Ultrasound-guided placement of the marker was performed in 64 patients (60%), and mammographic-guided placement was done in 43 patients (40%). Median localization time was 5 minutes (1–45), and in all cases except one, placement was successful on the first attempt. All Magseeds were placed less than 10 mm from the target lesion with 95% being within 5 mm (Table 2). For 21% of patients with 1 Magseed only, the distance from the skin to seed was estimated to be greater than 30 mm based on postprocedure mammogram. Histology was benign in 8% of cases; the remainder were malignant lesions including 23% with ductal carcinoma in situ, 59% invasive ductal carcinoma, 2% invasive lobular carcinoma, and 8% with other malignant lesions. There were 22 patients who received neoadjuvant systemic therapy.

Table 2.
Table 2.:
Radiographic Characteristics of Breast Lesions and Localization
FIGURE 3.
FIGURE 3.:
Types of breast lesions based on imaging findings. The majority of lesions in the “other” category were asymmetries.

There was a 100% Magseed retrieval rate with surgical excision with the Magseeds retrieved in the initial resected specimen in all cases including those with greater than 1 seed placed. Median time from localization to surgery was 1 day (0–20), and 51% of cases were scheduled and performed as the first surgery of the day. Median operative time was 15 minutes (4–47), and operative times were not longer for patients with more than 1 Magseed placed. For individual surgeons, mean operative times for the first 3 cases were no different than the remainder of cases they performed indicating that there was no significant learning curve associated with use of the Magseed system. All surgeons performed at least 5 cases. Five instances of the Sentimag probe not functioning properly intraoperatively were observed and resolved with replacement of the probe during the surgery. No device-related adverse events occurred as a result of this or otherwise. Figure 4 demonstrates intraoperative radiographs of the overall specimen and the sliced sections showing the Magseed, biopsy clip, and a surgical clip. Of the 98 malignant breast lesions, 9 (9%) cases had positive margins and 7 underwent a second procedure for margin re-excision. On unvariable analysis including age, breast density, type of target lesion, method of localization, histology, tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 receptor status, neoadjuvant chemotherapy receipt, and pathologic T category, age ≤50 years (25.0% vs 6.4%, P = 0.04), lesion histology (P = 0.03), and pathologic T category (P = 0.04) were significantly associated with positive margins. However, due to the low number of positive margin events, multivariable analysis could not be performed.

FIGURE 4.
FIGURE 4.:
Segmental mastectomy specimen radiographs. A, Whole specimen radiograph depicting the Magseed, biopsy clip, and surgical clip. B, Radiograph of sectioned specimen for intraoperative margin assessment.

Clinicians were surveyed to assess the ease of use of the Magseed system with respect to their role (Table 3). Radiologists rated the ease of placement very easy in 61% and fairly easy in 37%. All cases with 2 or 3 Magseeds being placed were rated as very easy or fairly easy to place by the radiologists. Surgeons rated the ease of transcutaneous localization as very easy or fairly easy in 93% of cases and, after incision was made, rated the ease of localization as very easy and fairly easy in 87%. There were 2 cases in which the surgeons were unable to localize the Magseed transcutaneously; however, after incision, there were no cases in which the Magseed could not be localized intraoperatively by the surgeon. Pathologists reported the ease of marker identification and retrieval in the specimen to be very easy or fairly easy in 96%.

Table 3.
Table 3.:
Survey of Clinicians

DISCUSSION

This prospective, phase IV trial demonstrated that localization of nonpalpable benign and malignant breast lesions with Magseed is safe and effective. The primary endpoint of Magseed retrieval rate was met with 100% of Magseeds retrieved surgically. Furthermore, it was shown that multiple Magseeds could be successfully placed and retrieved in a single surgical excision. There were no adverse events associated with the use of Magseed. Technical difficulties intraoperatively occurred in 5 cases due to the Sentimag probe not sensing the Magseed but resolved with changing the probe. We demonstrated that the Magseed could localize multiple types of target lesions accurately with 95% of Magseeds located within 5 mm of the target and 100% within 10 mm. Furthermore, in cases with a single Magseed located greater than 30 mm deep to the skin, surgeons were able to transcutaneously localize these deeper Magseeds very easily or fairly easily in nearly all cases. A steep learning curve can be a limitation to adopting new technologies; however, nearly all Magseeds were placed by the radiologist on the first attempt and duration of surgical cases did not demonstrate a significant learning curve. This was also the first study to assess clinician perspectives on the ease of use of Magseed, and radiologists, surgeons, and pathologists rated Magseed very or fairly easy to use in the majority of cases indirectly demonstrating a minimal learning curve.

Multiple retrospective and smaller prospective studies have demonstrated 100% Magseed retrieval rate.5,6,9–11 Zacharioudakis et al11 reported a prospective multicenter trial that enrolled 100 consecutive patients undergoing Magseed localization for surgical excision and compared them to 100 consecutive patients undergoing wire localization in the same time period. They reported 4 Magseed cases that were converted to wire localization before surgery: 2 cases in which the Magseed was misplaced and 2 where it could not be detected. In our study, there were no instances requiring change in localization technique or inability to detect the Magseed intraoperatively. Accuracy of localization is critical to surgical resection of nonpalpable breast lesions. Price et al5 showed that in 97% of cases, the marker was placed within 5 mm of the target which is comparable to our finding of 95% of Magseeds located within 5 mm. A retrospective, single institution study of 188 patients defined technical success as Magseed placement within 10 mm of the target and demonstrated this in 97% of cases.9 They reported 7 cases of mammographically placed seeds that migrated more than 1 cm from the target which they hypothesized to be secondary to the accordion effect (release of mammographic compression). In our cohort, 40% underwent mammographic placement with no cases of Magseed migration and all Magseeds were within 10 mm of the target.

Margin status is a key component in successfully performing breast conservation surgery. Lamb et al9 reported 22% of cases with positive or close margins after Magseed localization requiring re-excision, and Thekkinkattil et al10 reported a 15% re-excision rate. These rates vary in the literature but generally range from 20% to 24%.12 Although not undertaken in our study, previous studies comparing radioactive seed localization to wire localization have not demonstrated a statistically significant difference in positive margin rates or reoperation rates4,13 and our low rate of re-excision for positive margins is comparable to our previously published institutional re-excision rates.14 Therefore, the localization technique may not be a predictor of positive margins but rather positive margins are due to a variety of other factors.

One advantage of radioactive seeds and Magseeds is the decoupling of the marker placement and timing of surgery. However, in addition to the stringent regulatory licensing and processing associated with radioactive seed use, the state licensure also limits placement to 5 days before surgery.2 Conversely, the FDA has approved long-term placement of Magseed with no restrictions on length of time it can remain in the body. Price et al5 reported a mean time of 3 days from Magseed placement to surgery, and Thekkinkattil et al10 reported a mean time of 7 days though the majority were placed the day before surgery. In our study, there was a median time of 1 day between Magseed insertion and surgery, and placement of the seed in advance of the operative day facilitated first start cases. This can be a significant advantage to improving workflow efficiency in healthcare systems in addition to reducing the potential psychological stress on the patient undergoing multiple procedures on the day of surgery.

There are limitations of this study including that it was a single institution study at an academic cancer center with dedicated breast radiologists, breast surgical oncologists, and breast pathologists. However, our findings are similar to other studies indicating their generalizability. It is possible that there may have been selection bias because the surgeon could choose Magseed localization versus another method of localization. Our results suggest that all types of breast lesions including after receipt of chemotherapy could be accurately localized and surgically excised with 1 or more Magseeds. Another limitation is the single-arm design without a direct comparison to other breast localization techniques. A Cochrane review comparing radioactive iodine seed localization and radioguided occult lesion localization to wire localization concluded that there was insufficient evidence to support the use of 1 technique.4 There are advantages and disadvantages to wire localization and other technologies used for breast localization1; however, the techniques may be comparable with regard to many of the clinically relevant outcomes presented in this study. Thus, studies to examine cost-effectiveness and the impact of Magseed and other techniques on a healthcare system may provide data to help institutions decide which device to implement in their breast surgery program.

CONCLUSIONS

The Magseed system is a safe and effective technique for localization and excision of nonpalpable breast lesions and the findings of this study support its use. Future studies comparing Magseed to other localization techniques in terms of cost-effectiveness and patient-reported outcomes may be helpful to healthcare systems considering adoption of new localization devices.

ACKNOWLEDGMENTS

Authorship contributions are as follows: Drs Singh, Scoggins, Sahin, Hwang, Kuerer, Caudle, Mittendorf, Thompson, Bedrosian, Teshome, DeSnyder, and Meric-Bernstam made substantial contributions to conception and design, acquisition of data, interpretation of data, revision of the manuscript, and gave final approval of the version to be published. Dr Hunt made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data, drafting and revision of the manuscript, and gave final approval of the version to be published. Dr Singh made substantial contributions to acquisition of data, analysis and interpretation of data, drafting and revision of the manuscript, and gave final approval of the version to be published.

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