Feasibility and validation of the targeted axillary dissection technique in the axillary staging of breast cancer after neoadjuvant therapy: Definitive results.

AIM: to study the feasibility and value of "Targeted Axillary Dissection" (TAD) in cN1 breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), in order to avoid unnecessary axillary lymph node dissection (ALND). MATERIALS AND METHODS: Design: Prospective observational study. INCLUSION CRITERIA: Patients with histologically confirmed cN1 staging BC and treated with NACT between January 2016 and August 2019 who accomplished clinical response. METHOD: Fine-Needle Aspiration (FNA) positive axillary nodes were marked with a metallic clip prior to neoadjuvant treatment. All patients were summited to TAD and ALND. Analysis of data: We performed [1]: a feasibility analysis of clinical, radiological and pathological variables, as well as difficulties and complications of the TAD [2]; a diagnostic test study of the sentinel lymph node biopsy (SLNB), clipped lymph node biopsy (BCLIP) and their combination (TAD), using ALND as the Gold Standard. RESULTS: 60 patients were included. 43 patients (71.7%) had a complete clinical lymph node response to NACT. Neither limitations nor complications in clip placement were found. Intraoperative location of the clipped node was problematic in 7 cases (11.7%). The pathological complete response rate (pCR) was 30.5% (18 patients) and ypN0 staging rate was 38.3% (23 patients). Sensitivity values of each technique were: SLNB: 80.9% (95%CI: 61.8-100); BCLIP: 80.8% (95%CI: 63.7-97.8); TAD: 92.6% (95%CI: 80.9-100) with negative predictive values of: SLNB: 84.6% (95%CI: 68.8-100); BCLIP: 81.0% (95%CI: 63.7-97.8); TAD: 91.3% (95%CI: 77.6-100). CONCLUSION: TAD is feasible and valid to rule out axillary metastatic involvement in cN1 breast cancer patients who respond to NACT.

Development of a predictive score of axillary lymph node dissection based on targeted axillary dissection in patients with breast cancer diagnosis, affected lymph nodes, and neoadjuvant treatment.

AIM: To determine predictive factors of axillary lymph node dissection (ALND) results in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), and subsequent staging using Targeted Axillary Dissection (TAD). MATERIAL AND METHOD: Case-control study between January 2016 and August 2019. Patients with BC, cN1 staging, marked with a metallic clip prior to NACT, and subsequently staged with TAD and ALND were included. They were divided into 2 groups: ALND patients with or without metastatic involvement (group 1 and group 2, respectively). We carried out a univariate analysis comparing clinical, radiological, surgical and pathological variables, and a logistic regression, (dependent variable: positive result of ALND; independent variables: number of suspicious lymph nodes in diagnostic ultrasound, positive hormone receptors, HER2 positive, complete clinical-radiological response to NACT, positive TAD, and biopsy of ≤2 nodes in TAD). A score for prediction of a metastatic ALND was proposed, with an internal validation study. RESULTS: 60 patients were included: Group 1: 33 (55.0%); Group 2: 27 (45.0%). Tumor size (Odds Ratio (OR) = 1.67; 95%CI 1.02-2.74), number of suspected nodes in ultrasound (OR = 2.20; 95%CI 1.01-4, 77), HER2 positive (OR 0.04; 95%CI 0.003-0.54), clinical-radiological response to NACT (OR = 0.07; 95%CI 0.01-0.75), and positive TAD (OR 15.48; 95%CI 1.68-142.78) were independent predictors of a positive result in ALND. We developed a "positive ALND predictive score", with good calibration (Hosmer-Lemeshow test: p = 0.65), and discrimination (AUC = 0.93; 95% CI 0, 87-0.99), with highest Youden index (0.7) at cut-off point of 17% risk of positive ALND (sensitivity = 100%; specificity = 70%). CONCLUSION: Tumor size, number of suspected nodes, positive HER2, response to NACT, and metastatic TAD are independent predictors of ALND. The predictive score for positive ALND would be a good indicator to safely omit ALND.

Fluorescent DTPA-Silk Fibroin Nanoparticles Radiolabeled with 111In: A Dual Tool for Biodistribution and Stability Studies.

This work aims to provide an effective and novel dual tool for the biodistribution studies of biopolimeric nanoparticles by using modified silk fibroin nanoparticles as a model. This is an indispensable step in the evaluation of the applicability of biopolymeric nanoparticles as drug delivery systems. In this work, we report a new facile method for radiolabeling silk fibroin nanoparticles conjugated to the chelating agent diethylenetriamine pentaacetic acid and tagged with fluorescein isothiocyanate. Nanoparticles were characterized by means of dynamic light scattering, scanning electron microscopy, and infrared and fluorescence spectroscopy. The in vitro studies included stability in biological media and evaluation of the cytotoxicity of the nanoparticles in a cell culture. The in vivo study was focused on a scintigraphic study over 24 h conducted on New Zealand rabbits, after intra-articular injection of [111In]In-nanoparticles containing 8.03 ± 0.42 MBq. Biodistribution of the nanoparticles was also assessed ex vivo by fluorescence microscopy of post mortem biopsied organs. This radiolabeling method was reproducible and robust with high radiolabeling efficiency (∼80%) and high specific activity suitable for in vivo studies. Radiolabeled nanoparticles, having a hydrodynamic radius of 113.2 ± 2.3 nm, a polydispersity index of 0.101 ± 0.015, and a Z-potential of -30.1 ± 2.0 mV, showed an optimum retention in the articular space, without activity clearance up to 24 h post injection. Thus, an easy and robust radiolabeling method has been developed, and its applicability is demonstrated in vitro and in vivo studies, showing its value for future investigation of silk fibroin nanoparticles as versatile and stable (steady) local drug delivery systems for consideration as a therapeutic option, particularly in the treatment of joint disorders.

The problem of axillary staging in breast cancer after neoadjuvant chemotherapy. Role of targeted axillary dissection and types of lymph node markers. / El problema de la estadificación axilar en el cáncer de mama tras quimioterapia neoadyuvante. Papel de la disección axilar dirigida y tipos de marcadores ganglionares.

Targeted axillary dissection (TAD) consists of a new axillary staging technique that combines sentinel lymph node biopsy (SLNB) and clipped lymph node biopsy (CLNB) in the same surgery, in order to re-stage patients with breast cancer and positive axillary lymph nodes undergoing neoadjuvant chemotherapy (NAQT). Prior to the NAQT, the affected lymph node is punctured and a solid marker is left inside echo-guided, in order to biopsy it in the subsequent surgery. There are numerous types of markers: metallic (steel, titanium or polyglycolic acid clips), radioiodine or ferromagnetic seeds, which differ in the method of location (wire, gamma-detection or magnetic probe). The aim of this study is to perform a systematic review about the current status of the TAD, as well as to explain the different techniques and types of axillary marking, based on the current available evidence.

Validation of the targeted axillary dissection technique in the axillary staging of breast cancer after neoadjuvant therapy: Preliminary results.

AIM: To study the feasibility and validity of ultrasound-guided pre-chemotherapy marking of metastatic axillary lymph nodes followed by targeted axillary dissection (TAD), in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). MATERIAL AND METHOD: Prospective diagnostic test study conducted between January 2016 and March 2018. Patients with breast cancer and indication for NACT, cN1 or cN2 axillary staging, were included. A clip was placed in the affected lymph node prior to NACT. A sentinel lymph-node biopsy (SLNB) and a clipped lymph-node biopsy (BCLIP) were conducted, followed by axillary lymph node dissection (ALND). Location rate (LR) and negative predictive value (NPV) were evaluated, taking SLNB, BCLIP and their combination (TAD) as evaluated tests and metastatic involvement in the ALND specimen as the gold standard. RESULTS: Twenty-three patients were included in the study. Sentinel lymph node could only be detected in 19 cases (LR = 80.61%), whereas BCLIP was successful in 22 (LR = 95.65%). The sentinel lymph node coincided with the marked lymph node in 14 patients (60.9%). We found a NPV for the SLNB of 0.85 (95%CI: 0.61-1.0), whereas for TAD it was 1.00 (95%CI: 0.74-1.0). CONCLUSION: TAD is a feasible test for axillary restaging after NACT, with a higher success rate than SLNB.