Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Intraoperative excision of TAD lymph nodes followed by ALND in the same surgical session or secondary surgical intervention

Targeted axilllary dissection (TAD) followed by axillary lymph node dissection (ALND)

Oliver Halfmann

Dorothea Schindowski

Sherko Kuemmel, Prof. Dr.

Mattea Reinisch, Dr.

Due to high pathological complete remission (pCR) rates in both breast and lymph nodes (ypT0/Tis, ypN0) following neoadjuvant systemic therapy (NST) in many patients with initially clinically node-positive (cN+) breast cancer, the standard treatment of the axilla has changed from axillary lymph node dissection (ALND), which is associated with high morbidity, to less invasive, surgical approaches. In several studies, targeted axillary dissection (TAD) has presented with false-negative rates (FNRs) less than 5%, however, in patients with high initial lymph node involvement (≥ 3 clinically suspicious lymph nodes) TAD has not been thoroughly investigated.

The present prospective registry study aims to evaluate the FNR of TAD in patients with ≥ 3 initially suspicious lymph nodes and clinically node-negative status (ycN0) after NST in comparison to ALND.

Patients with triple-negative breast cancer (TNBC) or human epidermal growth factor receptor 2 (HER2) positive breast cancer achieved pCR rates of 50-70% following NST. In the multicenter prospective SenTa study (NCT03102307), the axillary pCR rate after the end of NST in 473 initially cN+ patients was 60.3%. Therefore, less invasive surgical techniques have been investigated to avoid the morbidity associated with ALND. One of these minimally invasive methods called TAD involves the combined intraoperative excision of the pre-NST marked most suspicious lymph node (target lymph node, TLN) and sentinel lymph nodes (SLNs). In a pooled analysis of 13 studies including 521 patients who had undergone TAD, the FNR of TAD was 5.2%.

The FNR of TAD in breast cancer patients with high initial lymph node (LN) involvement (≥ 3 clinically suspicious LNs) has so far hardly been investigated. In a very small cohort, a FNR of 0% was obtained for patients with 1-3 suspicious LNs (cN1, n = 10), 33% for patients with 4-9 suspicious LNs (cN2, n = 3) and 100% for patients with 10 or more suspicious LNs (cN3, n = 2). In addition, patients with high lymph node involvement are often excluded from some larger studies evaluating TAD or other axillary surgical approaches. In consequence, the FNR of TAD LNs in comparison to LNs obtained during ALND in the patient group with ≥ 3 clinically positive LNs needs to be evaluated in a larger cohort, since extensive initial LN involvement is associated with a higher probability that a false-negative result of TAD could cause one or more involved LNs to be left in the axilla, if only TAD and not ALND is performed.

TAD in Primary Breast Cancer With Initially ≥ 3 Suspicious Lymph Nodes

Prospective, Multicentric Registry Study Evaluating the False-negative Rate of Targeted Axillary Dissection (TAD) in Primary Breast Cancer With Initially ≥ 3 Suspicious Lymph Nodes Under Neoadjuvant Systemic Therapy (SenTa 2)

The FNR of TAD is calculated as the number of patients with histologically negative TAD lymph nodes (LNs) who were found to have positive LNs in the ALND specimen, divided by the total number of patients with positive LNs.

Preoperative detection rate (DR) of initially marked target lymph nodes (TLNs) on ultrasound images after the end of NST

Successful localization with e.g. wire, magnetic marker, or reflector clip of the marked TLNs

Successful intraoperative identification of at least one SLN and one TLN, including cases with TLN = SLN

Successful intraoperative identification of TLN(s)

Successful intraoperative identification of SLN(s)

The FNR of TLNB is calculated as the number of patients with histologically negative TLNs who were found to have positive SLNs and/or positive LNs in the ALND specimen, divided by the total number of patients with positive LNs.

The FNR of SLNB is calculated as the number of patients with negative SLNs who were found to have positive TLNs and/or positive LNs in the ALND specimen, divided by the total number of patients with positive LNs.

False-negative is defined as preoperative ycN0 status on axillary ultrasound images and pathological ypN+ after surgery

Proportion of patients with ipsilateral or contralateral recurrence in the breast and/or axilla occurring at any time after surgery.

Proportion of patients with distant recurrence occurring at any time after surgery.

iDFS is calculated as the time from surgery to the occurrence of either local recurrence, distant recurrence, second malignant disease (breast or different origin), or death from any cause.

OS is calculated as the time from surgery to death from any cause

Kliniken Essen-Mitte

Clinically affected lymph nodes cannot be biopsied or clip labeled. Patients are not suitable for TAD

Clinically affected lymph nodes can be biopsied and clip labeled. Needle biopsy reveals no axillary tumor spread. Patients are suitable for TAD

Clinically affected lymph nodes can be biopsied and clip labeled. Needle biopsy reveals axillary tumor spread. Patients are suitable for TAD

Registry of the rate of patients not suitable for TAD as initial CNB with clip placement of axillary lymph nodes is not possible and underlying medical contraindications, technical obstacles or miscellaneous reasons why needle biopsy and/or clip labeling of clinically affected lymph nodes cannot be done

Not suitable for TAD

Registry of surgical outcome measures of targeted resection of the clipped node with optional sentinel node biopsy or axillary lymph node dissection with or without preceding neoadjuvant chemotherapy

Suitable for TAD

Sherko Kümmel, MD

Johannes Holtschmidt, MD

Thortsen Kühn, MD

A downstaging of axillary tumor-spread can be achieved in about 40% of the patients receiving neoadjuvant chemotherapy (NACT). The impact of NACT on loco-regional tumor control has not yet been sufficiently investigated. Moreover the pathologic nodal status after NACT is a strong prognostic marker. Therefore it is most desirable to identify the approximately 40% of patients with pathologic complete response of the axilla, that could be spared from a potentially non beneficial axillary lymph node dissection (ALND). Attempts to identify these patients via sentinel lymph node biopsy (SLNB) after NACT have failed to provide acceptable false negative rates (FNR). The new concept of targeted axillary dissection (TAD) following NACT has shown promising results. Still multiple information about the clinical adoption of this procedure into clinical practice are missing. The SenTa registry trial is designed to assess the clinical implementation of TAD into general practice.

For decades the pathologic nodal status in early breast cancer has been of paramount importance, when evaluating the need for further adjuvant therapies. Nowadays tumor characteristics as receptor status and gene expression essays are increasingly included in this decision process. An increasing number of breast cancer patients are treated with neoadjuvant chemotherapy (NACT). A downstaging of axillary tumor-spread can be achieved in about 40% of the patients receiving NACT. The contribution of NACT to loco-regional tumor control is not fully integrated into the surgical treatment plan. The introduction of sentinel lymph node biopsy (SLNB) and the results of the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial led to a reduction in radicalness of axillary surgery in the adjuvant setting. The impact of NACT on loco-regional tumor control in the neoadjuvant setting has not yet been sufficiently investigated. Moreover the pathologic nodal status after NACT is a strong prognostic marker. Therefore it is most desirable to identify the approximately 40% of patients with pathologic complete response of the axilla and distinguish these patients from those with tumor residuals which might need additional postneoadjuvant treatment. So far attempts to identify these patients via SLNB after NACT have failed to provide acceptable false negative rates (FNR) as reported in the SENTINA (Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) trial and ACOSOG Z1071 trial.

Attempts have bee made to further improve FNR of SLNB after NACT in patients with clinically affected lymph nodes at initial presentation. A new concept of surgical axillary staging after NACT is the targeted axillary dissection (TAD). First results have shown to reduce FNR far below the desired threshold of 10%. In this procedure clinically suspicious lymph nodes are evaluated by core needle biopsy (CNB) or fine needle aspiration (FNA) before NACT. A clip is placed into the most suspicious appearing lymph node (target lymph node TLN) directly after biopsy. In case of proven metastasis surgical staging of the axilla is postponed to after completion of NACT. The targeted resection of the clipped node after NACT (target lymph node biopsy TLNB) displays a FNR of 2 - 4.2% according to first results published by Caudle et al. in 2016. In about 3 out of 4 patients the TLN equals a SLN if SLNB is performed simultaneously. The combination of TLNB and SLNB (together so called TAD) seems to further lower FNR. Cases in which tracer uptake in lymph nodes is impaired i.e. by tumor residuals and presumably result in a false negative SLNB can be covered by TLNB.

Clip placement in affected axillary lymph nodes for the purpose of following targeted resection has been implemented into international guidelines. But to date multiple insights into clinical application of TAD are missing. It is not known how often initial CNB/FNA of axillary lymph nodes and following clip placement is successful or has to be abandoned because of technical/medical contraindications. Moreover it is not known how often visualization of the clip after normalization of lymph node structures following NACT and month after initial clip placement is possible. Furthermore information about optimal clip material are lacking. In summary success rates for the targeted resection of the clipped node have to be investigated. Therefore the intraoperative detection rate of the clipped target lymph node is our primary outcome measure.

Patients with clinically affected lymph nodes at initial presentation are planned to be enrolled in multiple german breast centers. In accorndance to german guidelines it is aimed to evaluate the pathologic nodal status via CNB with following clip placement in all of these patients after informed consent. If CNB or clip placement cannot be achieved, technical/medical contraindications are recorded. As the SenTa trial is a registry trial, no strict directives for the further surgical treatment are made. If clip placement is successful, further procedures are left at the investigators choice according to initial pathologic nodal status and potential clinical response to NACT.

If no tumor manifestations are detected in initial CNB, SLNB with simultaneous targeted resection of the clipped node (TLNB) is recommended. The rationale for TLNB in this situation is a FNR of about 20% of initial CNB. On an individual basis upfront ALND can be offered.

If tumor manifestations are detected in initial CNB, targeted resection of the clipped node (TLNB) is strongly recommended because of obvious reasons. If NACT is not planned, upfront ALND should be offered. If patients are planned for NACT further procedures are left at the investigators discretion according to clinical response to NACT. Clinical response after NACT is assessed by axillary ultrasound and an optional needle biopsy if applicable. In case of clinical complete response, TLNB with simultaneous SLNB can be offered on an individual basis.

Registry Trial to Evaluate the Clinical Utilization of Targeted Axillary Dissection (TAD)

A Prospective, Multicenter, Registry Trial to Evaluate Utilization Frequency and Feasibility of Targeted Axillary Dissection (TAD) After Needle Biopsy and Clip Placement in Early Breast Cancer With Clinically Affected Lymph Nodes

Successful intraoperative detection and targeted resection of clip labeled target lymph node as confirmed by specimen radiography and/or surgeon

Rate of patients not suitable for TAD as initial CNB with clip placement of axillary lymph nodes is not possible and underlying medical contraindications, technical obstacles or miscellaneous reasons why needle biopsy and/or clip labeling of clinically affected lymph nodes cannot be done

Rate of CNB revealing tumor manifestations or lymph node tissue on histology out of all performed lymph node CNB

Essential requirement for targeted resection of the clipped target lymph node is the preoperative visualization of the clip for the purpose of guide wire localization

Rate of patients with intraoperative detection of at least one sentinel lymph node and the clip labeled target lymph node as confirmed by specimen radiography and/or surgeon

Rate of patients treated with upfront axillary dissection including resection of clipped node after completion of NACT

Clipped target lymph node does not contain tumor manifestations after NACT but lymph node metastasis is revealed by ALND

Sentinel lymph node does not contain tumor manifestations after NACT but lymph node metastasis is revealed by ALND

Successful intraoperative detection and resection of at least one sentinel lymph node and the clip labeled target lymph node as confirmed by specimen radiography and/or surgeon

Successful intraoperative detection and resection of at least one sentinel lymph node

Clip is located in a sentinel lymph node during TAD, hence the TLN equals a SLN

Number of excised lymph nodes during targeted axillary dissection (TAD) equals count of sentinel lymph nodes plus target lymph nodes

Number of excised clipped lymph nodes during target lymph node biopsy (TLNB) which are not sentinel lymph nodes

German Breast Group

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

Patients in whom the magnetic marker Magseed is used will be enrolled in this study arm and will undergo targeted axillary dissection.

Patients in whom the iodine seed 125I marker is used will be enrolled in this study arm and will undergo targeted axillary dissection.

Patients in whom the carbon suspension marker is used will be enrolled in this study arm and will undergo targeted axillary dissection.

The surgical treatment procedure of targeted axillary dissection performed in patients in whom the pathological lymph nodes have been marked using the examined and compared markers (magnetic marker Magseed, iodine seed 125I, carbon suspension)

Targeted axillary dissection

Jan Žatecký, MD

A multicentre prospective comparative study, comparing the use of various markers (magnetic marker Magseed, iodine seed 125I, carbon suspension) for marking a pathological lymph node in patients with breast carcinoma prior to neoadjuvant therapy and subsequent surgical treatment consisting of targeted axillary dissection.

There are two basic aims of the study

1. Prospective comparison of the reliability and accuracy of individual markers used for marking of a pathological axillary lymph node with subsequent targeted axillary dissection.
2. Comparison of the number of complications during localizing and detection of individual markers and postoperative complications.

In individual collaborating centers, these markers are commonly used in clinical practice for marking of a pathological lymph node in patients with breast carcinoma. The usual standard of practice and treatment will not be changed in any way; the patients will only be prospectively followed. The study will bring an answer to the question of which marker is the best for marking lymph nodes.

Apart from the basic demographic and other data (patient age, side of the body, size and characteristics of the tumor (typing, grading, staging), type and time of surgery, the incidence of complications during implantation or detection of the marker, number of lymph nodes, complications after surgery, and the final histological findings, also the following outcome measures will be observed:

* depth of marker implantation (measured in mm)
* marker migration (measured in mm)
* success-rate of resection of the marked lymph node - assessment, whether the lymph node was removed (yes/no) using the respective marker, expressed in percent of successful removal for the respective marker
* time from localizing the pathological lymph node using the marker to surgery (measured n days)

Ideal Marker for Targeted Axillary Dissection

Individual participant data may be made available to other researchers upon request.

The depth of marker implantation will be assessed and measured in millimetres

Marker migration will be assessed and measured in millimetres

Assessment, whether the lymph node was removed (yes/no) using the respective marker, expressed in percent of successful removal for the respective marker.

The time from localizing the pathological lymph node using the marker to surgery will be analysed and measured in days

Silesian Hospital in Opava

Masaryk Memorial Cancer Institute

EUC Clinic in Zlín

Institute for the Care of Mother and Child, Prague, Czech Republic

University of Ostrava

University Hospital Ostrava

During standard of care (SoC) surgery to remove breast cancer, study participants will undergo a sampling of lymph nodes in the axilla first and then complete removal of axillary lymph nodes under the arm.

A surgical procedure that opens the armpit (axilla) to identify, examine, or remove lymph nodes. Axillary dissection will be performed during SoC breast cancer surgery.

Axillary Dissection

Jornan Rodriguez Leyva

Susan Kesmodel, MD

The purpose of this research is to evaluate how to manage the axillary lymph nodes in patients with breast cancer. The investigators will determine if a sampling of the lymph nodes under the arm will give the information necessary to determine if fewer lymph nodes can be removed.

Prospective Evaluation of Targeted Axillary Dissection (TAD)

TAD: Prospective Evaluation of Targeted Axillary Dissection After Neoadjuvant Systemic Therapy in Patients With Breast Cancer With Advanced Nodal Disease at Diagnosis

The false negative rate of targeted axillary dissection after neoadjuvant systemic therapy (NST) in study participants. A false negative event will be defined as a case where the specific node (either the clipped node or the sentinel lymph node, depending on the analysis) does not show metastasis even though residual disease is identified in the other axillary nodes. The false negative rate will be computed as the number of false negative events divided by the total number of pathologically node-positive patients.

The sentinel lymph node identification rate is the number of study participants with at least one sentinel lymph node divided by total number of study participants.

The clipped lymph node identification rate is the number of study participants with at least one clipped lymph node removed divided by the total number of study participants with clipped lymph nodes.

The accuracy rate of imaging studies in determining response in the breast and axilla will be calculated as the sum of true responders on imaging and true non-responders on imaging divided by total number of study participants.

The number of participants with pCR will be reported. The percentage of patients with pCR will be calculated as the number of patients with a pCR divided by the total number of study participants. PCR is defined as the lack of all signs of cancer in tissue samples removed during surgery.

Number of participants experiencing treatment-emergent adverse events (AEs). AEs will be assessed by and assigned severity and treatment attribution by the treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.

University of Miami

Associate Professor of Clinical

Symptoms and General Pathology

Neoplasm Metastasis

Lymphatic Metastasis

Neoplastic Processes

Ultrasound of the axilla preoperative. Clipped biopsy proven positive node. I125 radioactive seed before surgery. Sentinel node biopsy using Tc99 +/- blue dye. Targeted Axillary Node Dissection performed at surgery

Sentinel Node Biopsy (SNB; using Tc99 +/- Blue dye) + Radioactive Seed Localisation (RSL) of clipped node using I125 seed = Targeted Axillary Dissection (TAD)

Targeted Axillary Dissection

Prospectively recorded preoperative ultrasound of the axilla. Number of suspicious nodes recorded. Biopsy and clipping of the positive node.

Ultrasound of the axilla

Jean-François Boileau, MD,MSc,FRCSC

Léamarie Meloche-Dumas, MD

Lucas Sidéris, MD

Erica Patocskai, MD

Isabelle Trop, MPH,FRCPC

Danh Tran-Thanh, MD,MSc,FRCPC

Mona El Khoury, MD

Stephanie Wong, MD,MPH,FRCSC

Francesca Marie Grazia Proulx, MD

Livia Florianova, MD,MSc,FRCPC

RATIONALE: It is now standard for most breast cancer patients with 1-2 positive sentinel nodes to avoid completion node dissection when eligibility criteria from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial are met. The National Comprehensive Cancer Network (NCCN) recently proposed to extend this indication to patients that present with biopsy proven node positive disease if only 1 or 2 suspicious nodes are found on imaging, these positive nodes are not palpable clinically, and the other eligibility criteria from the Z0011 study are otherwise met. However, this recommendation is based on an expert consensus and no study has yet confirmed the optimal method to stage the axilla in this patient population.

PURPOSE: Evaluate the technical success rate and accuracy of sentinel node biopsy (SNB) and the potential benefits of clipping and removing the biopsy proven node using radioactive seed localisation (RSL) (SNB+RSL = Targeted Axillary Dissection (TAD)) in patients with biopsy proven positive nodes, limited nodal disease in imaging and clinically negative axillary examination.

This is a prospective multicenter study. Patients with T1-2 Breast cancer and clinically negative axilla on palpation, 1-2 suspicious nodes on ultrasound, and a biopsy proven positive node (by core biopsy of fine needle aspiration) will have a radioactive seed (I125) placed in their clipped node before surgery. At the time of surgery, patients that are scheduled for breast conserving surgery or mastectomy will have sentinel node biopsy (SNB) using radioactive dye (Tc99) +/- blue dye as well as retrieval of the clipped node using radioactive seed localisation (RSL). Removal of the I125 radioactive seed in the clipped node will be performed before the Tc99 counts are performed to prevent "shine through" and biased measurements. Imaging of the surgical specimen will confirm retrieval of the clipped node. Prospectively recorded information on pre-operative axillary imaging, characteristics of the retrieved nodes in the operating room and detailed pathological analysis of each corresponding node will be performed. Completion node dissection (CND) is not mandatory in this study but recommended if the clipped positive node is not retrieved, if 4 nodes or more are positive or if 3 nodes are positive in the absence of axillary radiation. The benefits of adding RSL to SNB and the benefits of adding SNB to RSL staging of the axilla will be evaluated in this study and will help to better define the value of using TAD in this patient population.

Targeted Axillary Dissection (TAD) in Early-stage Node Positive Breast Cancer

Sentinel Node Biopsy and Targeted Axillary Dissection in Node-Positive Breast Cancer Patients With Clinically Negative Axilla

Recommended completion node dissection rate (CND) = false negative rate (FNR) + technical failure rate (TFR).

TAD CND (TAD FNR + TAD TFR) vs. SNB CND (SNB FNR + SNB TFR)

Evaluate if the addition of SNB to RSL improves the ability to identify patients with 3+ positive nodes that do not otherwise meet the ACOSOG Z0011 criteria and require further regional axillary therapy

Percentage of patients with successful removal of at least one node (using this method) where at least one positive node was not retrieved (using this method)

Percentage of patients with unsuccessful removal of at least one node using this method, including the clipped node

Percentage of patients with unsuccessful removal of at least one node using this method (clipped node or not)

Quebec Breast Cancer Foundation

Jewish General Hospital

MD, MSc, FRCSC, Surgical Oncologist, Associate Professor Surgery and Oncology, McGill University, Director JGH Breast Clinical Trials Group

Iron

All patients will receive Radioisotope according to standard of care. They will also receive SPIO in a timeframe of clinical convenience, depending on whether primary response is planned by means of MRI. For patients that are ycN0, SLND or TAD will be performed. For those that convert from cN1 to ycN0, the index lymph node will be marked with a paramagnetic marker. Axillary surgery will be undertaken with the magnetic technique and each retrieved lymph node will be controlled for radiation. Upon the completion of the procedure, a background control will be performed with the radioactive signal as guide, to ensure standard of care best practice. Any palpable lymph nodes that are not sentinels with either tracer may be removed at surgeon discretion but will be reported seperately.

SLND or TAD by the magnetic technique (SPIO)

Andreas U Karakatsanis, MD, PhD

The goal of this study was to assess the feasibility of SLND by superparamagnetic iron oxide nanoparticles (SPIO) in patients with early breast cancer planned for primary systemic therapy (PST) and whether this is affected by the timeframe of SPIO administration.

For this, patients with cN0/1 disease planned for PST received radioisotope as per routine on the day of surgery or the day before, and SPIO was injected in an extended timeframe, at any point from the day of surgery to before the induction of PST.

The main points to investigate are:

1. If the SPIO detection rate and concordance to the radiosotope are affected by time of SPIO injection
2. If the nodal yield and the accuracy of the procedure are affected

Superparamagnetic Iron Nanoparticles (SPIO) have shown comparable performance to the standard of Radioisotope (RI) +/- blue dye (BD) for Sentinel Lymph Node Detection in breast cancer, with the advantage of clinical convenience due to easier accessibility, disposal and injection days before surgery.

More interestingly, SPIO provides the possibility for delayed SLND in the setting of a preoperative diagnosis of DCIS, enabling SLN detection weeks after breast surgery, only when specimen pathology has demonstrated invasive cancer, as shown in the SentiNot study. The role of SPIO for SLND in the setting of primary systemic therapy (PST) has not been extensively investigated, while the timeframe from SPIO administration to successful SLN detection in a similar fashion to SentiNot, but in the setting of PST has yet to been defined.

Current evidence suggest that RI-based SLN detection is the accepted standard following PST, with RI-based dual mapping specifically recommended in cN+-to-ycN0 patients, when SLND or targeted axillary dissection (TAD) are performed, as the number of SLNs retrieved has been inversely linked to the false negative rate of the procedure.

Apart from the logistic benefits of SPIO administration prior to PST, an aspect of potential interest is the ability to map the axilla, before the fibrotic changes induced by chemotherapy and lymphatic remodelling occur, that are a concern, especially in the node-positive patients at presentation.

However, in this case, it is imperative to investigate that SPIO remains detectable after a prolonged period of administration and that it does not migrate to higher nodal echelons. While preliminary data suggested feasibility, the aim of this dedicated study was to investigate the width of timeframe of SPIO administration in patients undergoing PST and how SPIO-based detection and concordance to the RI are affected.

In this study, patients scheduled for SLND or TAD after surgery will undergo the procedure with RI as the standard of care and will moreover receive SPIO. The administration of SPIO will take place either on the preoperative period but after the completion of PST, or before the induction of PST. The reason for this is to create a wide time-frame to allow for conclusion with regards to whether the mapping of the axilla prior PST by SPIO is a feasible technique that will then be addressed in a dedicated trial.

Delayed SLND for Patients With Breast Cancer Undergoing Primary Systemic Treatment

A Feasibility Study on the Timeframe of Superparamagnetic Iron Oxide Nanoparticles Administration in Patients Receiving Primary Systemic Therapy for Early Breast Cancer

Patients have not been consented for IPD and separate consent should be sought for this. For any interest, contact andreas.karakatsanis@uu.se

The successful retrieval of at least two and at least three SLN detected by each tracer (SPIO or radioisotope) separately.

Any adverse events reported in relation to SPIO administration

This endpoint is necessary in ensuring that prolonged SPIO administration does not result in the retrieval of "false" SLNs, in the case that SPIO migrates to higher nodal echelons. As the radioisotope is the current standard of care, the concordance of SPIO to the radioisotope and its correlation with time of SPIO adminstration is the appropriate surrogate endpoint.

The successful retrieval of at least one SLN detected by each tracer (SPIO or radioisotope) separately.

The rate (patients with at least one SLN detected with both tracers/patients with at least one SLN detected with the radioisotope)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TAD in Primary Breast Cancer With Initially ≥ 3 Suspicious Lymph Nodes	NCT05462457	Breast Cancer Node-positive B...	Targeted axilll...	18 Years -	Kliniken Essen-Mitte
TAD in Primary Breast Cancer With Initially ≥ 3 Suspicious Lymph Nodes	NCT05462457	Breast Cancer Node-positive B...	Targeted axilll...	18 Years -	Kliniken Essen-Mitte
Registry Trial to Evaluate the Clinical Utilization of Targeted Axillary Dissection (TAD)	NCT03102307	Early Stage Bre...	Not suitable fo... Suitable for TA...	18 Years -	Kliniken Essen-Mitte
Ideal Marker for Targeted Axillary Dissection	NCT04580251	Breast Cancer	Targeted axilla...	18 Years -	University Hospital Ostrava
Prospective Evaluation of Targeted Axillary Dissection (TAD)	NCT04998682	Breast Cancer	Axillary Dissec...	18 Years -	University of Miami
Targeted Axillary Dissection (TAD) in Early-stage Node Positive Breast Cancer	NCT04671511	Breast Cancer F... Early-stage Bre... Lymph Node Meta... Axillary Metast... Sentinel Lymph ...	Targeted Axilla... Ultrasound of t...	18 Years -	Jewish General Hospital
Delayed SLND for Patients With Breast Cancer Undergoing Primary Systemic Treatment	NCT05985551	Breast Cancer Chemotherapy Ef... Sentinel Lymph ...	SLND or TAD by ...	18 Years -	Uppsala University
Targeted Axillary Dissection (TAD) in Early-stage Node Positive Breast Cancer	NCT04671511	Breast Cancer F... Early-stage Bre... Lymph Node Meta... Axillary Metast... Sentinel Lymph ...	Targeted Axilla... Ultrasound of t...	18 Years -	Jewish General Hospital

Spots Global Cancer Trial Database for targeted axillary dissection