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. 2022 Nov;4(6):e220053.
doi: 10.1148/rycan.220053.

Ultrasonographic Detection and Surgical Retrieval of a Nonmetallic Twinkle Marker in Breast Cancer: Pilot Study

James W Jakub  1 , Gina K Hesley  1 , Nicholas B Larson  1 , Michael J Yaszemski  1 , A Lee Miller 2nd  1 , James F Greenleaf  1 , Matthew W Urban  1 , Christine U Lee  1
Affiliations

Ultrasonographic Detection and Surgical Retrieval of a Nonmetallic Twinkle Marker in Breast Cancer: Pilot Study

James W Jakub et al. Radiol Imaging Cancer. 2022 Nov.

Abstract

Purpose To evaluate the short-term safety of a nonmetallic twinkle marker and compare its conspicuity at color Doppler US with that of standard breast biopsy clips and radioactive seeds by using B-mode US in axillary lymph nodes. Materials and Methods This prospective study (November 2020-July 2021) of participants with node-positive breast cancer who completed chemotherapy involved placing a twinkle marker at the time of preoperative radioactive seed localization. A five-point scoring system (1 = easiest, 5 = most difficult) was used to rate the ease of identifying the clip, seed, and twinkle marker on postlocalization sonograms, mammograms, specimen radiographs, and gross pathologic specimens. Descriptive statistics were used. Results Eight women (mean age, 57 years ± 16 [SD]) were enrolled. The median scores for US conspicuity of each device were 3.9 (range, 3.7-5.0) for the radioactive seed, 2.4 (range, 1.0-5.0) for the clip, and 2.0 (range, 1.0-4.3) for the twinkle marker. In six of eight participants, the twinkle marker was the most identifiable at US. The seeds, clips, and twinkle markers were scored "very easy" to identify on seven of eight postlocalization mammograms. The surgeon retrieved all eight twinkle markers 1-3 days after localization. In all 16 interpretations, the seeds, clips, and twinkle markers were rated as very easy to identify on specimen radiographs. The clip was the most difficult device to identify at pathologic examination in all participants, and the twinkle marker was the easiest to identify in seven of eight participants. Conclusion This pilot study demonstrates that the safety and ease of US detection of a twinkling tissue marker may be comparable to a biopsy clip. Keywords: Ultrasonography, US-Doppler, Breast, Localization, Surgery Clinical trial registration no. NCT04674852 © RSNA, 2022.

Keywords: Breast; Localization; Surgery; US-Doppler; Ultrasonography.

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Conflict of interest statement

Disclosures of conflicts of interest: J.W.J. Royalties or licenses from Sorrento Therapeutics; patent co-inventor on a pending patent application for the Twinkling Marker (PCT patent application no. US2020/051844); member of the Melanoma Surgical Advisory Board for Novartis Oncology (May 2020); member of the Corporate Relations Committee for the American Society of Breast Surgeons (voluntary, unpaid position). G.K.H. Patent co-inventor on a pending application on the Twinkling Marker (U.S. patent Application No. 17/398 778). N.B.L. No relevant relationships. M.J.Y. Patent co-inventor on a pending patent application for the Twinkling Marker (PCT patent application no. US2020/051844). A.L.M. Patent co-inventor on a pending patent application for the Twinkling Marker (PCT patent application no. US2020/051844). J.F.G. Patent co-inventor on a pending patent application for the Twinkling Marker (PCT patent application no. US2020/051844); patent co-inventor on a pending application on the Twinkling Marker (U.S. patent Application No. 17/398 778). W.U. U.S. continuation-in-part patent application (17/398 778) filed August 10, 2021 (also incorporates 2019-414 and 2020-192); provisional patent application (62/903 078) filed on September 20, 2019; PCT patent application (PCT/US2020/051844), filed on September 21, 2020 (primary, with 2020-192 as secondary); U.S. patent application (17/762,018) filed on March 18, 2022; European patent application (20786193.1) filed on March 31, 2022; U.S. continuation-in-part patent application (17/398 778) filed on August 10, 2021 (also incorporates 2020-192 and 2021-198). C.U.L. Co–primary investigator on internal grant from the Mayo Clinic Center of Individualized Medicine Imaging Biomarkers Program, no conflicting relationships, activities, or employment with this funding source; patent co-inventor on a pending patent application on the Twinkling Marker (PCT patent Application No. US2020/051844); patent co-inventor on a pending application on the Twinkling Marker (U.S. patent Application No. 17/398 778).

Figures

Twinkling markers. (A) A vial of twinkling markers is next to a vial of nonradioactive seeds. (B) Several twinkling markers placed in US coupling gel with air bubbles are difficult to identify confidently, but the markers demonstrate a conspicuous twinkling signature at (C) color Doppler US.
Figure 1:
Twinkling markers. (A) A vial of twinkling markers is next to a vial of nonradioactive seeds. (B) Several twinkling markers placed in US coupling gel with air bubbles are difficult to identify confidently, but the markers demonstrate a conspicuous twinkling signature at (C) color Doppler US.
Data collection form. The five-point Likert scoring scale was used to assess ease of US detection of the seed, the previously placed clip, and the twinkle marker.
Figure 2:
Data collection form. The five-point Likert scoring scale was used to assess ease of US detection of the seed, the previously placed clip, and the twinkle marker.
Ease or difficulty of visualizing twinkle marker at US, based on independent US interpretations on a five-point Likert scale (see Figure 2 for scale) by three reviewers. The scores for each of the 24 interpretations and the median scores are shown. R1 = reviewer 1 (breast radiologist), R2 = reviewer 2 (breast radiologist), R3 = reviewer 3 (sonographer).
Figure 3:
Ease or difficulty of visualizing twinkle marker at US, based on independent US interpretations on a five-point Likert scale (see Figure 2 for scale) by three reviewers. The scores for each of the 24 interpretations and the median scores are shown. R1 = reviewer 1 (breast radiologist), R2 = reviewer 2 (breast radiologist), R3 = reviewer 3 (sonographer).
Air affecting US conspicuity of the seed. (A) The tip of the introducer needle containing the seed and the marker is well-visualized (arrow). (B) As air is introduced at the target site during deployment of the seed and twinkle marker, the margin of the lymph node is not well identified. Moreover, neither the seed nor the twinkle marker are well-visualized at B-mode imaging. (C) At color Doppler US, the twinkle marker is easily identified by its twinkling signature.
Figure 4:
Air affecting US conspicuity of the seed. (A) The tip of the introducer needle containing the seed and the marker is well-visualized (arrow). (B) As air is introduced at the target site during deployment of the seed and twinkle marker, the margin of the lymph node is not well identified. Moreover, neither the seed nor the twinkle marker are well-visualized at B-mode imaging. (C) At color Doppler US, the twinkle marker is easily identified by its twinkling signature.
Imaging and visualization of devices across the spectrum of care in a 67-year-old woman with right breast invasive ductal carcinoma (estrogen receptor and progesterone receptor negative, HER2/neu positive) and (A) a metastatic right axillary lymph node (arrow). (B) A Tumark Q clip (arrow; Somatex Medical Technologies) is deployed into the positive node at the time of fine-needle aspiration (FNA) and (C) confirmed (arrow) on postclip mammogram on axillary tail view. During iodine-125 (125I) seed localization, neither the seed nor the twinkle marker are conspicuous at (D) B-mode US, but at (E) color Doppler US, the twinkle marker is evident (arrow). (F) Axillary tail view postlocalization mammogram shows successful localization of the Q clip (arrow), and surgical specimen shows the twinkle marker, the Q clip, and the 125I seed. NAC = neoadjuvant chemotherapy.
Figure 5:
Imaging and visualization of devices across the spectrum of care in a 67-year-old woman with right breast invasive ductal carcinoma (estrogen receptor and progesterone receptor negative, HER2/neu positive) and (A) a metastatic right axillary lymph node (arrow). (B) A Tumark Q clip (arrow; Somatex Medical Technologies) is deployed into the positive node at the time of fine-needle aspiration (FNA) and (C) confirmed (arrow) on postclip mammogram on axillary tail view. During iodine-125 (125I) seed localization, neither the seed nor the twinkle marker are conspicuous at (D) B-mode US, but at (E) color Doppler US, the twinkle marker is evident (arrow). (F) Axillary tail view postlocalization mammogram shows successful localization of the Q clip (arrow), and surgical specimen shows the twinkle marker, the Q clip, and the 125I seed. NAC = neoadjuvant chemotherapy.
Gross specimen. The seed, Turamark Q clip (Somatex Medical Technologies), and twinkling marker are identified in the specimen (arrows).
Figure 6:
Gross specimen. The seed, Turamark Q clip (Somatex Medical Technologies), and twinkling marker are identified in the specimen (arrows).
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