Clipped Node Research Articles

Intraoperative Ultrasound-Guided Excision of Axillary Clip in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Therapy (ILINA Trial) : A New Tool to Guide the Excision of the Clipped Node After Neoadjuvant Treatment.

The accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) has been improved with the placement of a clip in the positive node prior to treatment. Several methods have been described for clipped node excision during SLNB after NAT. We assessed the feasibility of intraoperative ultrasound (IOUS)-guided excision of the clipped node during SLNB and investigated whether the accuracy of SLNB is improved. After approval by the Institutional Ethics Committee, all breast cancer patients undergoing NAT had an US-visible clip placed in the positive node. The ILINA trial consisted of IOUS-guided excision of the clipped node along with SLNB and axillary lymph node dissection (ALND). Forty-six patients had a clip placed in the positive node. In two (4.3%) cases, the clip could not be seen prior to surgery and the patient underwent ALND; however, the clipped node was successfully removed by IOUS-guided excision in 44 patients. Thirty-five patients (79.5%) underwent SLNB along with IOUS-guided excision of the clipped node and ALND, and were subsequently included in the ILINA trial. Nine patients were not included (five patients with SLNB only and four patients with ALND without SLNB). SLNB matched the clipped node in 27 (77%) patients. The false negative rate for the ILINA protocol was 4.1% (95% confidence interval 0.1-21.1%). IOUS-guided excision of the axillary clipped node after NAT was feasible, safe, and successful in 100% of cases. The ILINA trial is accurate in predicting axillary nodal status after NAT.

Localizing the Clipped Node in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Chemotherapy: Early Learning Experience and Challenges.

Placement of a clip in the positive node in patients presenting with node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) allows resection of the clipped node at SLN surgery and improves the accuracy of surgical staging. We sought to evaluate our experience with SLN surgery with resection of the clipped node since incorporation into our practice. With Institutional Review Board approval, we evaluated all breast cancer patients with a percutaneous biopsy-positive axillary lymph node, clipped at the time of diagnosis, who underwent NAC followed by surgery. Fifty-six node-positive patients were identified. Eighteen patients (32.1%) underwent axillary dissection without sentinel lymph node (SLN) surgery, and 38 patients underwent SLN surgery (18 patients underwent SLN surgery alone, and 20 patients underwent SLNsurgery andaxillary lymph node dissection). In 25patients, preoperative localization of the clipped node with an 125I radioactive seed was attempted. This was performed by ultrasound guidance in 18 cases (72%), computed tomography (CT) guidance in two cases (8%), and was unable to be localized in five cases (20%). In all 20 seed-localized cases, the seed and the clipped node were resected along with additional SLNs. In 14 patients without seed localization (nine not attempted, five unable to be localized), the clipped node was resected in 11 cases (79%)-as one of the SLNs (6), by intraoperative ultrasound (4), or by palpation (1). Overall, the clipped node was resected in 31/34 (91%) cases. Preoperative ultrasound localization of the clipped node was successful in 72% of cases. Alternatively, the clipped node can be identified by preoperative CT, routine SLN surgery, intraoperative ultrasound, or palpation.

Radiologic Mapping for Targeted Axillary Dissection: Needle Biopsy to Excision.

The purpose of this article is to describe the feasibility and safety of a multidisciplinary approach to imaging-guided axillary staging that facilitates personalized, less invasive surgical management of the axilla through targeted axillary dissection in patients with biopsy-proven nodal metastasis undergoing neoadjuvant chemotherapy. Axillary nodal status, critical in breast cancer staging, affects prognosis and treatment. As the paradigm shifts toward minimally invasive therapy, a clip marker is placed in the biopsied metastatic node for patients with N1-N2 disease undergoing neoadjuvant chemotherapy to facilitate targeted axillary dissection of the clipped node. This node is typically localized with a radioactive seed at sentinel lymph node dissection to determine whether further axillary surgery is warranted.

Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection.

Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.

Abstract P2-01-02: Methods impacting the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4,N1-2) who receive neoadjuvant chemotherapy – Results from a prospective trial – ACOSOG Z1071 (Alliance)

Abstract Background: The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial (Alliance) reported a false negative rate (FNR) of 12.6% with sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy in women presenting with node-positive breast cancer. Proposed methods to decrease the FNR include clip placement in the positive node at initial diagnosis with confirmation of resection of the clipped node at surgery and inclusion of residual metastatic cells identified by immunohistochemistry (IHC) for cytokeratins and disease measuring <0.2mm on H&E in the definition of node positivity after chemotherapy. Herein we evaluate the impact of these methods on FNR. Methods: Z1071 was a prospective multi-institutional trial in which women with clinical T0-4,N1-2,M0 breast cancer underwent both SLN surgery and axillary dissection (ALND) after neoadjuvant chemotherapy. The primary endpoint defined nodal metastasis as disease >0.2mm on H&E. Slides were submitted for central IHC staining when H&E-negative, unless performed locally. For this analysis, we expanded the definition of node positivity to include metastases less than 0.2mm on H&E and metastatic deposits identified by IHC. In 171 cases, a clip was placed in the node at initial biopsy and in these cases the SLNs and ALND were evaluated by x-ray or pathology to document clip location. FNR in the clip cohort is reported using the primary endpoint definition of node positive disease (>0.2mm on H&E). Results: In the 113 cases where the clip was found in the SLN the FNR was 6.4% (1.8-15.5%). In the 29 cases where the clip was found in the ALND specimen, the FNR was 22.2% (6.4-47.6%). IHC was available on 470 of 525 patients with cN1 disease and 2 SLNs resected. Using the definition of H&E metastasis >0.2mm, the FNR in these patients was 11.3% (34/301, 8.0-15.4%) which decreased to 8.7% (27/311, 5.6-11.8%) when including any disease <0.2mm. SLNs from 16 patients had disease <0.2mm in size. Seven patients previously classified as false negative SLN changed to true positive with identification of disease in the SLN. Nine patients changed from node-negative to node-positive with the only disease being <0.2mm disease found in the SLN. Nodal pathologic complete response rate changed from 36.0% to 33.8% with the inclusion of metastases <0.2mm. NResidual disease identified in SLNs or ALNDFNR (%)95% CINode positive definitionSLN metastases >0.2mm by H&E470301 (64.0%)11.38.0-15.4SLN metastasis any size on IHC or H&E470311 (66.2%)8.75.6-11.8Clip locationClip in SLN11462 (54.4%)6.41.8-15.5Clip in ALND2918 (62.1%)22.26.4-47.6Clip location unknown2920 (69.0%)14.33.0-36.3Clip not placed354207 (58.5%)13.59.1-18.9 Conclusion: Placement of a clip at initial diagnosis of node positive disease with identification of the clip during the SLN surgery reduces the FNR. Use of IHC with inclusion of metastases <0.2mm in the definition of residual nodal disease in women with node positive breast cancer after chemotherapy also improves the accuracy of SLN surgery. Use of one or both of these methods should be considered when performing SLN in this setting. Citation Format: Judy C Boughey, Karla V Ballman, William F Symmans, Linda M McCall, Elizabeth A Mittendorf, Gretchen M Ahrendt, Lee G Wilke, Bret Taback, Kelly K Hunt. Methods impacting the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4,N1-2) who receive neoadjuvant chemotherapy – Results from a prospective trial – ACOSOG Z1071 (Alliance) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-02.