Would Removal of All Ultrasound Abnormal Metastatic Lymph Nodes Without Sentinel Lymph Node Biopsy Be Accurate in Patients with Breast Cancer with Neoadjuvant Chemotherapy?

Removal of sonographically abnormal (up to 3) metastatic clipped nodes, without sentinel lymph node biopsy, could accurately predict axillary status in breast cancer patients receiving neoadjuvant chemotherapy. ypT and the first clipped node status were statistically significant factors for nodal pathologic complete response. This novel approach requires validation in larger studies. In patients who have node-positive breast cancer, neoadjuvant chemotherapy could result in nodal pathologic complete response (pCR) and avoid an axillary lymph node dissection (ALND). Axillary staging, in such cases, can be performed using targeted axillary dissection (TAD) with a low false negative rate. However, identification of sentinel lymph nodes (SLNs) after chemotherapy can be difficult, and currently, it is the standard to remove only one clipped node in TAD. We aimed to determine if removal of all sonographically abnormal metastatic clipped nodes, without SLN biopsy, could accurately predict the axillary status post neoadjuvant chemotherapy. Patients with breast cancer with one to three sonographically abnormal metastatic axillary nodes were prospectively recruited. Each abnormal node had histology and clip insertion before neoadjuvant chemotherapy. After chemotherapy, the patients underwent removal of clipped nodes using the Skin Mark clipped Axillary nodes Removal Technique (SMART) and ALND. Fourteen patients were recruited, having a total of 21 sonographically abnormal metastatic nodes, with nine, three, and two patients having 1, 2, and 3 malignant nodes clipped, respectively. Mean age was 55.5 years; 92.9% and 57.1% of patients had invasive ductal carcinoma and grade III tumors, respectively; and 35.7% patients achieved nodal pCR. The first clipped node predicted the axillary status with a false negative rate of 7.1%. Adding to this another second clipped node, the false negative rate was 0%. Pathologic tumor staging after neoadjuvant chemotherapy (ypT) (p = .0390) and the first clipped node pathological response status (p = .0030) were statistically significant predictors for nodal pCR. Removal of sonographically abnormal metastatic clipped nodes using SMART, without sentinel lymph node biopsy, could accurately predict axillary status. This finding needs validation in larger studies.

Lim GH ，Gudi M ，Teo SY ，Ng RP ，Yan Z ，Lee YS ，Allen JC Jr ，Leong LCH ... -  《-》

Initial results of a novel technique of clipped node localization in breast cancer patients postneoadjuvant chemotherapy: Skin Mark clipped Axillary nodes Removal Technique (SMART trial).

Removal of clipped nodes can improve sentinel node biopsy accuracy in breast cancer patients post neoadjuvant chemotherapy (NACT). However, the current methods of clipped node localization have limitations. We evaluated the feasibility of a novel clipped node localization and removal technique by preoperative skin marking of clipped nodes and removal by the Skin Mark clipped Axillary nodes Removal Technique (SMART), with the secondary aim of assessing the ultrasound visibility of the various clips in the axillary nodes after NACT. Invasive breast cancer patients with histologically metastatic axillary nodes, going for NACT, and ≤3 sonographically abnormal axillary nodes were recruited. All abnormal nodes had clips inserted. Patients with M1 disease were excluded. Post-NACT, patients underwent SMART and axillary lymph node dissection. Specimen radiography and pathological analyses were performed to confirm the clipped node presence. Success, complication rates of SMART, and ultrasound visibility of the various clips were assessed. Twenty-five clipped nodes in 14 patients underwent SMART without complications. The UltraCor Twirl, hydroMARK, UltraClip Dual Trigger, and UltraClip were removed in 13/13 (100%), 7/9 (77.8%), 1/2 (50.0%), and 0/1 (0%), respectively (P = .0103) with UltraCor Twirl having the best ultrasound visibility and removal rate. Removal of three clipped nodes in the same patient (P = .0010) and deeply seated clipped nodes (P = .0167) were associated with SMART failure. Skin Mark clipped Axillary nodes Removal Technique is feasible for removing clipped nodes post-NACT, with 100% observed success rate, using the UltraCor Twirl marker in patients with <3 not deeply seated clipped nodes. Larger studies are needed for validation.

Lim GH ，Teo SY ，Gudi M ，Ng RP ，Pang J ，Tan YS ，Lee YS ，Allen JC Jr ，Leong LCH ... -  《Cancer Medicine》

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.

Caudle AS ，Yang WT ，Krishnamurthy S ，Mittendorf EA ，Black DM ，Gilcrease MZ ，Bedrosian I ，Hobbs BP ，DeSnyder SM ，Hwang RF ，Adrada BE ，Shaitelman SF ，Chavez-MacGregor M ，Smith BD ，Candelaria RP ，Babiera GV ，Dogan BE ，Santiago L ，Hunt KK ，Kuerer HM ... -  《-》

Feasibility of targeted axillary dissection for de-escalation of surgical treatment after neoadjuvant chemotherapy in breast cancer.

Targeted axillary dissection, which combines sentinel lymph node biopsy with removal of the proven involved node noted during the staging process, has been shown to improve axillary staging and decrease false negative rates after neoadjuvant chemotherapy in patients with breast cancer. The main goal of this study was to assess the ability to identify and remove the clipped node and the false negative rate of targeted axillary dissection. We performed a prospective study among patients with biopsy-confirmed nodal metastases who received neoadjuvant chemotherapy. A clip was placed on the sample node prior systemic therapy. After neoadjuvant chemotherapy, all patients underwent sentinel lymph node biopsy (dual tracer), localization and excision of the clipped node and axillary lymph node dissection. The clipped node was preoperatively localized in all cases placing an iodine-125 seed guided by ultrasound. The pathology of the sentinel nodes and clipped node was compared with other nodes. A total of 455 patients with invasive breast cancer were studied. Of the 148 patients with NAC, 32 met the eligibility criteria and were enrolled in the study. Mean age at diagnosis was 52.3 years. Systematic lymphadenectomy was performed in all patients, with an average of 14.3 lymph nodes removed. Detection rate of the clipped node alone was 96.9%, and 100% for targeted axillary dissection. Ability of clipped node alone to predict nodal status showed a FNR of 10,5% while SLNB alone performed by dual tracer and targeted axillary dissection, showed FNRs of 5.3% and 5.0%, respectively. Sentinel lymph nodes matched clipped node in 23 patients (74.2%). In node positive breast cancer patients, targeted axillary dissection is a reliably approach for axillary staging after neoadjuvant chemotherapy. The preoperative location of the clipped node is mandatory to increase the detection rate and optimize the results of the technique.

Aragón-Sánchez S ，Ciruelos-Gil E ，López-Marín L ，Galindo A ，Tabuenca-Mateos MJ ，Jiménez-Arranz S ，Colmenero-Hernández M ，Oliver-Pérez MR ... -  《-》

Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy.

Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.

Cabıoğlu N ，Karanlık H ，Yılmaz R ，Emiroğlu S ，Tükenmez M ，Bademler S ，Şimşek DH ，Kantarcı TR ，Yirgin İK ，Bayram A ，Dursun M ... -  《World Journal of Surgical Oncology》