Audit of Targeted Sentinel Node Biopsy (TSNB) in Patients With Limited Nodal Disease Undergoing Primary Surgery

NCT ID: NCT07085442

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-01-17

Study Completion Date

2032-12-31

Brief Summary

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Axillary ultrasound scan (AUS) is routinely employed in the UK for preoperative axillary staging and can diagnose approximately 50 - 80% of node positive patients when combined with percutaneous needle biopsy techniques (either core-biopsy or fine-needle aspiration cytology). It is recognised that nodal burden is generally higher in clinically node negative patients with abnormal nodes on AUS and confirmed on needle-biopsy to be histologically positive than patients diagnosed as node positive on sentinel node biopsy (SNB). However, up to 40% of biopsy-proven node positive patients are found to have fewer than 3 involved nodes on subsequent axillary lymph node dissection (ALND) and are potential candidates for less extensive axillary surgery with axillary radiotherapy (ART) rather than ALND. The total number of abnormal nodes on ultrasound is a key predictor of overall nodal tumour burden.

The AMAROS and OTOASOR trials randomised patients with up to 2 positive sentinel nodes to either ALND or ART. These trials were conducted around the turn of the millennium and before routine use of AUS and therefore would have included a significant number of patients who were radiologically node positive (cN1). Likewise, the ACOSOG Z0011 trial that randomised a similar group of patients to either ALND or observation only, did not incorporate routine AUS and would have included some (radiological) cN1 patients. These trials revealed no adverse impact on disease-free or overall survival from omission of completion ALND.

Targeted axillary dissection (TAD) was introduced a few years ago to reduce the false negative rate of SNB following neoadjuvant chemotherapy (NACT) and has been standardised as part of the ongoing ATNEC trial \[ClinicalTrials.govNCT04109079\]. This technique for axillary staging after NACT is increasingly being adopted in the UK and elsewhere. TAD is technically more straightforward and less challenging in patients undergoing primary surgery with no concerns about clip migration consequent to nodal shrinkage as part of treatment response to NACT. Furthermore, the risk of under-treating the axilla is offset by the protocol: if no disease is identified in the targeted nodes (false-negative case), then patients proceed to ALND, thereby ensuring adequate treatment. Unlike TAD following NACT, the presence of viable tumour within the sampled nodes is mandatory and finding fibrosis is irrelevant except as a response to nodal biopsy per se.

Current ASCO guidelines support both SNB and TAD as staging options for patients with ultrasound-detected, biopsy-confirmed nodal disease. The Edinburgh randomised trials comparing four-node sampling with ALND demonstrated significantly lower arm morbidity with node sampling, supporting TAD as a clinically appropriate alternative in this patient population.

The UK-ANZ POSNOC trial randomised 1,900 patients with \<3 macrometastases to either no further axillary treatment or additional axillary treatment. The study included cN1 patients with biopsy-confirmed nodal metastases who underwent sentinel node biopsy or TAD. Patients with \<3 macrometastases on final histology were randomised to receive no further axillary treatment or proceed with additional axillary treatment (ALND or ART). POSNOC trial will answer whether further axillary treatment provides any benefit in patients with low volume nodal disease on SNB or TAD.

Notably, patients with biopsy-confirmed metastases and \<3 macrometastases on SNB/TAD are biologically and clinically similar to patients with normal AUS who are later found to have low-volume disease on SNB. Clinical decision-making and patient outcomes are driven by tumour biology and overall disease burden rather than the method of nodal disease detection. Furthermore, AUS sensitivity is operator dependent and whether FNA or core biopsy was used to sample the node. A patient considered node negative on AUS by one radiologist may be diagnosed with core biopsy confirmed nodal metastases with another radiologist. Pending the results of POSNOC trial, patients with less than 3 macrometastases are generally advised further axillary treatment, and ART is preferred over ALND to reduce the risk of lymphoedema.

NodeSMART is a prospective audit collecting data on all patients undergoing TAD in the primary surgery setting. Its goal is to audit surgical outcomes and benchmark them against - a) Comparing technical outcomes with those from sentinel node biopsy in the primary surgery setting and TAD performed after neoadjuvant chemotherapy. b) Assessing rates of arm lymphoedema and disease progression relative to findings from the AMAROS and Z11 trials, and the POSNOC trial once results are available. The term "Targeted Axillary Dissection" is somewhat misleading in this context, as the marked (biopsied) node is removed alongside sentinel nodes - not in isolation. NodeSMART therefore refers to the procedure more accurately as Targeted Sentinel Node Biopsy (TSNB).

Detailed Description

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Guidelines for node marking Sites are advised to follow the same standards used in the ongoing ATNEC breast cancer trial. At least three nodes should be removed to allow adequate assessment of nodal tumour burden.

Timing The node may be marked at the time of needle biopsy or at a separate visit.

Single vs multiple node marking It is not necessary to mark more than one node, even if multiple nodes are biopsied or appear malignant. The most abnormal-appearing node should be marked.

Black dye node marking Inject 0.2-0.4 ml of black dye into the cortex of the node Do not inject around the node or into the needle tract

If the marked node is not found or if multiple black nodes are identified the surgeon may stop once a total of four nodes have been removed

Conditions

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Breast Cancer Axillary Lymph Nodes Dissection Axillary Metastases Sentinel Lymph Node Biopsy (SLNB) Node Positive Breast Cancer Axilla; Breast Axillary Ultrasound

Keywords

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Targeted Axillary Dissection Targeted Sentinel Node Biopsy NodeSMART Breast Cancer Sentinel Node Biopsy Axillary Lymph Nodes Dissection Axillary Node Clearance

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients with biopsy proven nodal metastases (cN1) and not receiving neoadjuvant chemotherapy

Patients with T1 or T2 tumours with biopsy proven nodal metastases (cN1) and with ≤2 abnormal nodes on axillary ultrasound

Targeted Sentinel Node Biopsy (TSNB)

Intervention Type PROCEDURE

Targeted Sentinel Node Biopsy will be performed according to routine local practice. The procedure has been standardised for the post-NACT setting as part of the ongoing ATNEC trial. Sites are advised to follow the ATNEC protocol in the primary surgery setting, using either a dual- or single-tracer sentinel node biopsy technique, with localisation and removal of the marked biopsy proven positive node, and removal of at least 3 nodes.

Interventions

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Targeted Sentinel Node Biopsy (TSNB)

Targeted Sentinel Node Biopsy will be performed according to routine local practice. The procedure has been standardised for the post-NACT setting as part of the ongoing ATNEC trial. Sites are advised to follow the ATNEC protocol in the primary surgery setting, using either a dual- or single-tracer sentinel node biopsy technique, with localisation and removal of the marked biopsy proven positive node, and removal of at least 3 nodes.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* cT1-2N1M0 breast cancer
* FNA or core biopsy confirmed axillary nodal metastases
* ≤2 abnormal nodes on imaging
* Undergo a dual tracer or single tracer sentinel node biopsy along with removal of the marked node (Targeted Sentinel Node Biopsy, TSNB)
* 1 or 2 macrometastases identified in the removed nodes, with at least three nodes removed
* If the sentinel node(s) cannot be localised on SNB: axillary node sampling should be performed, the patient will be eligible if 1 or 2 macrometastases are identified in the removed nodes, with at least three nodes removed.
* If the node is not marked or the marked node is not removed, the patient will be eligible if 1 or 2 macrometastases are identified in the removed nodes, with at least three nodes removed.

Exclusion Criteria

* Neoadjuvant chemotherapy
* Previous ipsilateral axillary nodal surgery
* cT3-4 breast cancer
* ≥3 abnormal nodes on imaging
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospitals of Derby and Burton NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Dr Amit Goyal

Chief Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Amit Goyal

Role: STUDY_CHAIR

University Hospitals of Derby and Burton NHS Foundation Trust

Locations

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Burnley General Teaching Hospital

Burnley, , United Kingdom

Site Status RECRUITING

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status RECRUITING

Royal Derby Hospital

Derby, , United Kingdom

Site Status RECRUITING

Gartnavel General Hospital

Glasgow, , United Kingdom

Site Status RECRUITING

Wycombe Hospital

High Wycombe, , United Kingdom

Site Status RECRUITING

Liverpool University Hospitals NHS Foundation Trust

Liverpool, , United Kingdom

Site Status RECRUITING

Royal Alexandra Hospital

Paisley, , United Kingdom

Site Status RECRUITING

Mersey and West Lancashire Teaching Hospitals

St Helens, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Amit Goyal

Role: CONTACT

Phone: 01332 786958

Email: [email protected]

Facility Contacts

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Inder Kumar

Role: primary

Eleftheria Kleidi

Role: primary

Emanuele Garreffa

Role: primary

Laszlo Romics

Role: primary

Fiona Tsang-Wright

Role: primary

Julia Henderson

Role: primary

Laura Arthur

Role: primary

Leena Chagla

Role: primary

Other Identifiers

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PID 46

Identifier Type: -

Identifier Source: org_study_id