Feasibility of Preoperative Axillary Lymph Node Marking with a Clip in Breast Cancer Patients before Neoadjuvant Chemotherapy: A Preliminary Study

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1 [ABS-0078] GBCC 2018 Feasibility of Preoperative Axillary Lymph Node Marking with a Clip in Breast Cancer Patients before Neoadjuvant Chemotherapy: A Preliminary Study Eun Young Kim 1, Kwan Ho Lee 1, Yong Lai Park 1, Chan Heun Park 1, In Young Youn 2, Seon Hyeong Choi 2, Yoon Jung Choi 2, Shin Ho Kook 2 Department of Surgery 1 and Radiology 2 Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine

2 Introduction Introduction Axilla restaging after neoadjuvant chemotherapy The extent of persistent axillary nodal disease after neoadjuvant chemotherapy (NAC) - established prognostic marker for locoregional recurrence and survival However, no clear consensus for reliable method (SLNB vs ALND) of restaging the axilla after NAC to confirm conversion to negative lymph node status Kuerer HM et al. Ann Surg Oncol Von Minckwitz G. et al. J Clin Oncol. 2012

3 Introduction

4 Introduction Targeted axillary dissection after neoadjuvant chemotherapy To decrease false negative rate (FNR), targeted axillary dissection has been proposed NCCN Guidelines Version Marking of sampled axillary nodes with a tattoo or clip should be considered to permit verification that the biopsy-positive lymph node has been removed at the time of definitive surgery

5 Introduction 1. Mayo Clinic Clip placement in the positive node at initial diagnosis 2. Netherlands Radioactive iodine ( 125 I) seeds placement to axillary lymph node 3. MD Anderson Cancer Center Clip placement in the positive node at initial diagnosis

6 Introduction Accuracy of targeted axillary dissection after neoadjuvant chemotherapy ACOSOG Z1071 MARI TAD No of patients Identification rate of clip in SLN 82.9% (141/170) 97.0% (97/100) 60.2% (115/191) FNR of clipped node 6.8% 7.0% 4.2% Boughey JC et al. Ann Surg Donker M. et al. Ann Surg Kuehn T et al. Lancet Oncol. 2013

7 Introduction Purpose To determine the feasibility of image-guided marker- clip placement in axillary lymph nodes (ALNs) for breast cancer on upon initial presentation To assess the reliability of this method with SLNB for axillary restaging after NAC

8 Materials and Methods Patients and Methods Prospective study from June 2015 to August Women aged from years who were diagnosed as breast cancer - Suspicious axillary LNs (thickened cortex or absent hilum) on US or PET-CT - US-guided FNA or core needle biopsy on LNs before initiation of NAC - Underwent NAC followed by surgery Exclusion criteria - Disease progression during NAC - Pregnant or plan for pregnancy - Patients refusal

9 Materials and Methods US-guided clip insertion Surgical clips (LigaClip) was inserted into the suspicious lymph node before NAC One day after the procedure and one day before surgery - unilateral digital mammography (MLO) to confirm the location of clip

10 Materials and Methods Wire localization of marker-clipped nodes 1 hour before surgery, a 21-G 7.5-cm hooked wire was inserted to retrieve the clips

11 Materials and Methods Wire localization of marker-clipped nodes Cone-beam CT (CBCT) was performed for the selected region of interest After hook- wire localization - repeatedly acquired CT images to confirm the location of the marker clip

12 Materials and Methods SLN and marker-clipped lymph node surgery After excision of the marker- clipped LNs - intraoperative palpation, inspection of the specimen by a surgeon, specimen radiography confirmed that the excised LNs contained the clip Conventional SLNB proceeded using dual tracers

13 Materials and Methods Pathologic assessment The nodal specimens evaluated intraoperatively - to identify marker-clipped LNs and SLNs Axillary LN dissection (ALND) proceeded - if more than two LNs (including marker-clip LNs and SLNs) were found to be metastatic during intraoperative frozen biopsy

14 Results Patient characteristics N = 20 Age, mean, y 44.6±7.3 (29-58) Clinical tumor size, 3.9±1.6 ( ) mean, cm Suspicious LNs on US Tumor histology IDC ILC DCIS Histologic grade unspecified Tumor subtype ER/PR-positive, HER2-negative ER-positive, HER2-positive HER2-enriched Triple-negative NAC regimen AC-T AC-TH TCHP Type of breast surgery Partial mastectomy Total mastectomy N =

15 Results Clip insertion and wire localization Total of 24 clips inserted in 20 patients -1 marker clip insertion :16 patients, 2 marker clips insertion : 4 patients Wire localization of marker clipped LNs was successfully performed in all 24 clips 23 clips were successfully retrieved intraoperatively (identification rate of marker clipped LNs, 23/24 =95.8%) However, 1 clip could not be found and retrieved intraoperatively - possibly due to loosening of the anchored hook The location of the clip that we failed to retrieve was confirmed on the 6-month follow-up chest CT at the placement site, without migration

16 Results Surgical Procedure and Pathologic Outcomes Size of marker-clipped LN, mean, cm Clips identified in SLN 17 Clips identified in ALN 6 SLNB performed 12 SLNB and ALND performed 8 N = ±0.7 ( ) No. of marker-clipped LNs 1.1±0.3 (1-2) removed, mean No. of SLNs removed, mean 2.2±1.8 (1-7) No. of ALNs removed, mean 6.7±5.2 (1-13) Pathological tumor size, mean, cm Pathological tumor response Complete (no residual tumor) Residual DCIS only Residual infiltrating ca 1 cm Residual infiltrating ca > 1 cm Pathological response of LN No residual tumor Metastatic residue N = ±2.0 (0-9.5) pcr of both primary tumor, LN 3

17 Results Clinicopathologic staging and pathologic status of ALNs before and after NAC Case Prechemo Clinical stage Postchemo Clinical stage Pathologic stage Prechemo Marker-clipped LN Postchemo Marker-clipped LN SLN ALN 1 T2N1 T1N1 ypt1n0 Negative Negative Negative Negative 2 T3N1 T2N0 ypt2n0 Negative Negative Negative 5 T1N1 T0N0 ypt0n0 Negative Negative Negative 6 T3N1 T3N0 ypt3n0 Negative Negative Negative 7 T2N1 T1N0 ypt0n0 Negative Negative Negative 10 T2N1 T2N1 ypt2n0 Negative Negative Negative 13 T2N1 T1N1 ypt1n0 Negative Negative Negative 17 T4N1 T2N0 ypt0n0 Negative Negative Negative Negative 19 T3N1 T2N1 ypt1n0 Negative Negative Negative

18 Results Clinicopathologic staging and pathologic status of ALNs before and after NAC Case Prechemo Clinical stage Postchemo Clinical stage Pathologic stage Prechemo Marker-clipped LN Postchemo Marker-clipped LN SLN ALN 3 T3N1 T2N1 ypt1n0 Positive Negative Negative Negative 4 T2N1 T1N0 ypt1n0 Positive Negative Negative 8 T2N1 T1N0 ypt1n1 Positive Positive Positive Negative 9 T2N2 T1N1 ypt1n1 Positive Positive Negative Positive 11 T2N2 T1N0 yptisn2 Positive Positive Positive Positive 12 T3N1 T2N1 ypt1n0 Positive Negative Negative 14 T2N1 T1N1 ypt2n1 Positive Positive Negative Negative 15 T2N1 T1N1 ypt1n1 Positive Positive Negative 16 T2N2 T1N1 ypt2n2 Positive Positive Negative Positive 18 T2N1 T2N1 ypt1n0 Positive Negative Negative 20 T2N1 T0N0 yptisn1 Positive Positive Negative

19 Results All patients were underwent follow-up exams for axillary recurrence until March, 2018 (mean : 24.3 months) Disease-free status of the axilla was confirmed in all 20 patients No complications (bleeding, hematoma formation, nerve injury) were reported during clip insertion or wire localization No intraoperative or postoperative complications were reported

20 Conclusion Conclusion Image-guided marker-clip placement on positive ALNs before NAC and removal with SLNB is technically feasible and safe This procedure can improve the accuracy of the residual disease evaluation of axilla, especially in patients who have negative SLNB results It can also identify candidates for limited axillary surgery after neoadjuvant chemotherapy

21 Conclusion Kim EY et al. World J Surg. 2017

22 Thank you for your attention