Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Anti-Infective Agents

Methylene Blue

Formaldehyde

Patients with non-metastatic, biopsy and clipped locally advanced breast cancer will start systemic chemotherapy as per institutional best practices. Patients with a clinical complete response will be consented for SLNB followed by immediate ALND. Patients with persistent suspicious clinical adenopathy will be consented for ALND alone. All patients regardless of response to NAC will undergo ALND as per current institutional practices.

Patients undergoing SLNB followed by ALND will have the procedure performed by study the co-PI at OAUTH who is trained in the performance of SLNB. Histopathologic assessment of the breast and axillary contents will follow a standardized reporting procedure, including the assessment of residual cancer burden in both the breast and the axilla. Presence or absence of residual disease will be reported separately for the SLNB specimens, clipped node and remaining axillary contents.

The SLNB will be performed with 5 ml of undiluted methylene blue injected in equal aliquots, peri-tumoral, followed by a 5-minute massage prior to skin incision. Sentinel nodes will be defined as those that have uptake / visible blue staining or suspicious palpable nodes at the discretion of the operating surgeon. Sentinel nodes will be placed in formalin and sent separately. This will be followed by an immediate completion ALND, which will be similarly placed in formalin and sent separately from the SLNB specimen. Specimen radiographs will be performed on all specimens to confirm location of clip within SLNB vs. ALND specimens.

Sentinel lymph Node Biopsy

Gregory Knapp, MD

Olalekan Olasehinde, MD

Olalekan Olasenhinde, MD

In sub-Saharan Africa, breast cancer patients often present with advanced disease. In my previous research which evaluated over 600 patients from a prospective institutional data base, about 64% of women with a new diagnosis of breast cancer presented with locally advanced disease, including clinically positive axillary adenopathy. Our data also suggests that similar to African American women, triple negative breast cancer (TNBC) is common in Nigeria (43.5%).

The overall goal of the project is to evaluate the ability of existing technology in Nigeria to safely de-escalate axillary surgery in the management of locally advanced breast cancer patients. Currently, the standard-of-care for breast cancer patients with palpable axillary adenopathy (clinical N1 disease without evidence of distant metastases) at presentation in Nigeria is neoadjuvant systemic therapy followed by a modified radical mastectomy. This includes a complete axillary lymph node dissection (ALND). However, data from high-income countries however show that up to 85% of patients initially presenting with cN1 disease can be converted to cN0 (i.e. no palpable adenopathy) following NAC. These patients can thus safely undergo sentinel lymph node biopsy (SLNB) with up to 50% of these having pathologic complete response in the lymph nodes. In this patient population, both methylene blue and radio-isotope localization with Tc-99 sulphur colloid are required to ensure adequate performance of the SLNB to stage the axilla(i.e. false negative rate ≤10%). Although widely available in high-income countries, radio-isotope localization is not readily available in Nigeria. This project will explore an alternative to dual agent SLNB localization using readily available resources and multi-disciplinary collaboration in a lower-income environment. De-escalation of axillary surgery in high-income countries has significantly decreased operative morbidity and improved patient reported outcomes without compromising survival. However, context specific research and data from resource limited environments is needed to translate the benefit of de-escalation to sub-Saharan Africa.

The overall goal of my research is to promote the delivery of guideline-concordant breast cancer care to Nigerian breast cancer patients in a pragmatic manner. This project is novel in that the investigators are challenging the existing paradigm of dual agent localization, which is appropriate for a high-income setting, but completely out of reach and thus inapplicable in Nigeria despite the obvious need. I will leverage the African Research Group for Oncology (ARGO) breast cancer data base at OAUTHC and other existing research infrastructure to pursue the following specific aims: Aim 1: Determine the false negative rate of of axillary Ultrasound + single agent sentinel Lymph node biopsy in staging the axilla in cN1 patients who become cN0. The investigators will consent patients with complete clinical complete response (clinical assessment and targeted US) following NAC, for SLNB followed by immediate ALND. Presence or absence of residual disease will be reported separately for the SLNB and the ALND specimens. Positive axillary disease will be defined in a binary manner as any invasive disease (including isolated tumor cells) or not. Using ALND reporting as the gold standard, the investigators hypothesize a FNR of less than 10% following SLNB. Aim 2: To determine the proportion of patients with complete axillary LN Clinical \&Pathological cR post NAC. The proportion of patients who return negative for cancer cells following SLNB and or ALND will be determined based on the number of patients with preoperative node positive disease. Both overall pCR and subgroup analysis based on receptor status will be done. The investigators will also assess the concordance of pre-operative clinical and radiographic (i.e. targeted axillary US) assessment of lymph node status with and pathologic lymph node status after NAC. The investigators hypothesize a pCR rate of 50% following completion of NAC

This study will build on the peer-reviewed analysis of our own prospective data demonstrating a high incidence of locally advanced disease and chemo-sensitive subtypes (i.e. TNBC), which suggest that a large proportion of our patients may be candidates for de-escalation. The impact of de-escalation would be profound. Preliminary research into lymphedema as a result of ALND in our patient population suggest an incidence of \> 35%. The proposed study will provide a strong foundation for future studies evaluating the implementation of this strategy and other resource compatible interventions on breast cancer outcomes in Nigeria.

De-escalating Axillary Surgery in Breast Cancer Patients in Nigeria

De-escalating Axillary Surgery After Neoadjuvant Chemotherapy in Node Positive Breast Cancer Patients in Nigeria

• False negative rate (FNR) of pre-op axillary US and single agent SLNB post-NAC for axillary staging

• Incidence of axillary lymph node clinical and pathologic complete response in patient receiving NAC in Nigeria

• Concordance of pre-operative clinical, radiographic and pathologic lymph node status after NAC

• Performance of pre-operative axillary US to stage the axilla in node positive patients who are cN0 disease after NAC

• Performance of single agent SLNB using methylene blue to stage the axilla in node positive patients who are cN0 disease after NAC

Obafemi Awolowo University

Nova Scotia Health Authority

The biopsied node will be tattooed at the time of needle biopsy (fine needle aspiration or core biopsy) or separate visit under ultrasound guidance.

Tattooing (marking) of biopsied node with carbon dye (SPOT dye) at the time of fine needle aspiration or core biopsy or separate visit under ultrasound guidance. The dye will be injected in the cortex of the node and the perinodal tissue under ultrasound guidance. Patients will undergo standard (routine) armpit surgery and may receive neoadjuvant chemotherapy as planned by the clinical team. This could be removal of a few lymph glands (sentinel node biopsy) or removal of all the lymph glands (axillary lymph node dissection) in the armpit. The surgeon will try to identify and remove the tattooed lymph gland at the time of planned armpit surgery.

Tattooing of biopsied node

Amit Goyal, MS, MD, FRCS

The primary aim of this prospective, multicentre study is to determine whether the involved node can be marked using black carbon dye and successfully identified at the time of surgery. The secondary aims are to determine the concordance between the tattooed node and sentinel node, migration of black dye into other nodes, and false-negative rate of tattooed node (in patients undergoing ALND after NACT).

Pretreatment evaluation of axillary lymph nodes and marking of biopsied nodes in patients with newly diagnosed breast cancer is becoming routine practice. Tagging of biopsied axillary lymph nodes with metal markers, similar to what is done for suspicious breast lesions, is being adopted in clinical practice. The need to mark a positive axillary lymph node becomes especially relevant in cases where neoadjuvant chemotherapy (NACT) is anticipated so that these nodes may be identified at the time of surgery. Measures that improve both the accuracy of nodal evaluation after NACT and the ability to assess treatment response are desirable in order to tailor therapies for breast cancer treatment. The investigators sought to test tattooing of biopsied axillary lymph nodes with a sterile black carbon suspension (Spot dye). The concept is based on the experience in the gastrointestinal tract wherein tattooing is widely used for marking lesions or tumours biopsied during endoscopy. India ink tattoos of colonic lesions remain identifiable over a long period of time. Spot is routinely used in the UK for tattooing gastrointestinal tract lesions and is used to mark the axillary lymph nodes in breast cancer by some centres in the US and Europe. The intraoperative success of identifying tattooed axillary lymph nodes and their concordance to sentinel nodes will be determined.

Carbon Dye Tattooing of Biopsied Axillary Node in Breast Cancer

Pre-ATNEC - A Multicentre Prospective Feasibility Study of Carbon Dye Tattooing of Biopsied Axillary Node and Surgical Localisation in Breast Cancer Patients

Proportion of patients in whom tattooed node/s were identified.

Concordance rate: defined as the percent of patients in whomthe tattooed node is the sentinel node.

The number of black nodes at the time of sentinel node biopsy or axillary lymph node dissection.

University Hospitals of Derby and Burton NHS Foundation Trust

Associate Professor

The group includes patients who have malignant axillary lymph nodes which are proven by biopsy

The group includes patients who have benign axillary lymph nodes which are proven either by biopsy or follow-up

Each participant has undergone to ultrasound and biopsy procedure if they have suspicious lymph node in axillar region

Ultrasound and biyopsy

Pelin Seher Oztekin, Assoc. Prof.

102 patients who have suspicious ALNs were included in our prospective study, which was approved by a tertiary health care facility ethics committee. Each suspicious lymph nodes (LNs) were examined with PDUS and SMI in terms of distribution, appearance and number of vascular structures and the still images were stored. Subsequently, imaging findings were re-evaluated after histopathological or follow-up results and were compared between benign and malign groups. In addition, we revealed the diagnostic perfomance of using the each possible combination of these features in PDUS and SMI. Finally, two radiologists with 22 years and 4 years of experience analyzed the images and interobserver agreement was assessed

MATERIAL AND METHOD Patient The hospital's ethics committee approved this single-center prospective study (E-93471371-514.10). 139 female patients, ages 18 to 74, who had suspicious lymph nodes in the axilla during a breast ultrasound examination at our clinic between April 2021 and April 2022 were included in the study. 20 patients did not come back for follow-ups, 4 patients' ultrasonographic images were not sufficient diagnostic quality, and 13 patients were excluded from the study because the biopsy result was not diagnostic and the patient did not undergo re-biopsy. As a result, 108 lymph nodes from 102 patients were included in the study, and 37 patients were excluded.

Patients who were male, under the age of 18, underwent axillary lymph node dissection, had active infection in the axillary region, were diagnosed with histopathologically confirmed axillary lymph node metastasis, had received known chemotherapy or radiotherapy to the axillary region, or did not sign the informed consent form were excluded from the study. Patients who had their pathology results unavailable or who later decided not to participate in the study were also excluded.

Ultrasonographic Evaluation Suspicious axillary lymph nodes in the patients included in the study were evaluated with Toshiba Aplio a (Toshiba Medical Systems Corporation, Tokyo, Japan) ultrasound (US) device and 14-18 MHz high frequency linear probe. Gray scale US, PDUS and SMI images of the lymph nodes were stored. PRF and gain settings were adjusted to prevent from artifacts and to obtain the highest amount of signal while images were taken. In both Doppler methods, these parameters remained unchanged. The routine examination time for each patient extended 1-2 minutes by the SMI evaluation. At the end of the evaluation, a histological assessment using a 21G fine needle aspiration (FNA) biopsy or core biopsy (16-18G) from the relevant lymph nodes, or follow-up with US was performed, depending on the clinical suspicion. Any lymph nodes that regressed or disappeared throughout the US follow-up period of 1-3 months were considered benign. The lymph nodes that remained stable or progressed were evaluated through histopathological sampling. In case of non-diagnostic biopsy, patients were recalled and FNA/core biopsy was repeated. Cytology and pathology specimens were evaluated by a pathologist with at least 10 years of experience. Before the histopathological diagnosis, all patients were prospectively evaluated with ultrasonography by a radiologist blinded to the patient's clinic and history, and images were taken. After the pathology results, PDUS and SMI images were re-evaluated and the findings were compared with each other and pathology results. Finally, two radiologists with 22 years and 4 years of experience evaluated the images in terms of separately determined features without knowing the patient's clinical information and pathology result. The results were compared with each other in order to assess interobserver agreement.

Both PDUS and SMI assessed vascular patterns based on the number of internal vessels, the distribution (avascular/central/peripheral/mixed) and appearance (normal, dysplasic, avascular) of internal vessels. On SMI, both monochrome (mSMI) and color (cSMI) images were assessed. If there was diffuse cortical thickening of the lymph node, the entire cortex was included the images. Likewise if there was an asymmetric cortical thickening, images focused on that part.

Cortical flow signals were taken into account while internal vascularity was quantified. The lymph nodes with no vascular signals in the cortex were classified as avascular, the nodes with peripheral vascular signals as peripheral, the nodes with vascular signals extending from the hilus to the cortex as central, and the nodes with vascular signals in both the periphery and the central as mixed. To evaluate the morphology of the vessels, the signals with smooth, symmetrical hilar extension were considered as normal, the eccentric signals were identified as diplasic, and the lymph nodes without a signal were regarded as avascular.

Statistical Analysis In the study, mean and standard deviation were used for continuous variables, while frequency and percentage values were used when specifying categorical variables. The Kolmogorov-Smirnov and Shapiro Wilk test was used to evaluate the homogeneity of the patient distribution. Student t-test and Mann Whitney U test were used for continuous variables. Chi-square test or Fisher's exact chi-square test was used to evaluate categorical features In order to evaluate the diagnostic performance of each investigated feature of Doppler methods in the differentiation of benign and malignant lymph nodes, the area under the curve (AUC) was calculated separately by receiver operating characteristic (ROC) analysis, depending on whether they were used individually or together. Logistic regression analysis was used to determine the significance value when the features were used together. In addition, sensitivity, specificity, positive predictive value(PPV), negative predictive value (NPV) and accuracy of each method were evaluated.

The Kohen Kappa test was used for categorical features in both SMI and PDUS to assess interobserver agreement. Intragroup correlation coefficient test was used to compare vascular numbers. Chi-square test or Fisher's exact chi-square test was used to evaluate vascular properties between benign and malignant categories after consensus.

All statistical analyses was performed with SPSS version 25.0 (IBM Corp. Armonk, NY: USA. Released 2017). P value \<0.05 was considered statistically significant.

Benign-Malign Differentiation of Axillary Lymph Nodes: The Role Of Superb Microvascular Imaging

Benign-Malign Differentiation Of Axillary Lymph Nodes: The Role Of Superb Microvascular Imaging

The number of vascularity in axillary lymph nodes are assessed via inspection of the images of Superb Microvascular Imaging and Power Doppler Ultrasound by observers. Countable vascular signals are noted for each lymph nodes

Vascular distributions in axillary lymph nodes are assessed via inspection of the images of Superb Microvascular Imaging and Power Doppler Ultrasound by observers and are categorized as avascular, central, peripheral and mix.

Vascular appearance in axillary lymph nodes are assessed via inspection of the images of Superb Microvascular Imaging and Power Doppler Ultrasound by observers and are categorized as normal/central,eccentric, avascular.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
De-escalating Axillary Surgery in Breast Cancer Patients in Nigeria	NCT06039956	Breast Cancer Axilla; Breast	Sentinel lymph ...	18 Years - 70 Years	Nova Scotia Health Authority
Carbon Dye Tattooing of Biopsied Axillary Node in Breast Cancer	NCT03640819	Sentinel Lymph ... Breast Cancer Tattoo; Pigment... Axilla; Breast	Tattooing of bi...	18 Years -	University Hospitals of Derby and Burton NHS Foundation Trust
Benign-Malign Differentiation of Axillary Lymph Nodes: The Role Of Superb Microvascular Imaging	NCT05927727	Diagnosis Axilla; Breast	Ultrasound and ...	18 Years - 74 Years	Ankara Education and Research Hospital

Spots Global Cancer Trial Database for axilla; breast