Implementation of Indocyanine Green to Identify Sentinel Lymph Nodes During Surgery for Breast Cancer

NCT07146295 | Recruiting

• 2 other identifiers: NL87551.100.2410390172310041
• Study Type: interventional
• Target: 1,760
• Locations: 1 country
• Sites: 7

Brief Summary

The goal of this clinical trial is to learn how to successfully introduce a new method for finding the sentinel lymph node during breast cancer surgery into routine hospital care. The method uses a dye called indocyanine green (ICG) and a special camera to see the lymph node. The sentinel lymph node is the first lymph node that cancer is likely to spread to. In the Netherlands, about 1 in 7 women develops breast cancer. Finding out whether cancer has spread to the lymph nodes is important for planning treatment and predicting outcomes. The current standard method for sentinel lymph node biopsy (SLNB) uses a radioactive tracer called radioisotope technetium-labeled (99mTc)-nanocolloid. While accurate, this method has several drawbacks: it exposes patients to radioactivity, requires an extra hospital visit or travel to another hospital due to limited nuclear medicine facilities, and is not sustainable. Surgeries using 99mTc can only take place on certain days due to logistical issues, and the signal from 99mTc can be disturbed by the tumor marker placed in the breast. ICG works as well as 99mTc for SLNB and offers several advantages: it is given during surgery (no extra visit needed), produces no radiation, and reduces costs. However, it is still not widely used in the Netherlands because hospitals may not be familiar with it or unsure how to make the switch. This study will introduce ICG step-by-step in several Dutch hospitals and evaluate how to make the change as smooth and effective as possible. It will take place in three stages: I) SLNB with 99mTc only (current practice); II) SLNB with both 99mTc and ICG (transition phase); III) SLNB with ICG only (full implementation). All study procedures take place during planned surgery, with no extra hospital visits. After surgery, participants will receive a short questionnaire (10-15 minutes) to share their experiences with the procedure. Their feedback, combined with input from healthcare providers, will help researchers develop a uniform medical protocol, an implementation guide, and educational materials for surgeons and surgical trainees. The aim is to make ICG widely available across the Netherlands, ensuring that care is less burdensome, more sustainable, and more cost-effective, while keeping treatment accessible in local hospitals.

Conditions

Breast Cancer; Sentinel Lymph Node Biopsy (SLNB); Sentinel Lymph Node Detection; Sentinel Lymph Node; Lymphatic Metastasis; Fluorescence Imaging; Indocyanine Green (ICG); Radioisotopes; Lymph Node Mapping

Keywords

Breast cancer; Sentinel lymph node biopsy; Lymphatic metastasis; Indocyanine green; Techetium nanocolloïd; Fluorescence imaging; Surgical oncology; Lymph node mapping; Implementation; Radioisotope

Outcome Measures

Primary Outcomes (1)

• Adoption of ICG for sentinel lymph node biopsy (SLNB)

  Proportion of SLNB procedures performed using indocyanine green (ICG) only, compared to the total number of SLNB procedures perfomed, using any tracer, on the target population in the observational cohort of phase III. Adoption will be assessed using hospital administrative data, with cross-checking against the prospective screening and inclusion log.

  During Phase III, the post-implementation period, which is the final 9 months for hospitals in cluster 1, final 6 months for cluster 2, and final 3 months for cluster 3, within the 18-month trial.

Secondary Outcomes (17)

• Fidelity of ICG-fluorescence implementation

  Phase III; intraoperative survey completed immediately after each SLNB procedure.

• Appropriateness of ICG-fluorescence

  A questionnaire is administered to healthcare providers in each participating hospital during the 3rd month of Phase III, corresponding to month 12 for cluster 1, month 15 for cluster 2, and month 18 for cluster 3.

• Feasibility of ICG-fluorescence implementation

  A questionnaire is administered to healthcare providers in each participating hospital during the 3rd month of Phase III, corresponding to month 12 for cluster 1, month 15 for cluster 2, and month 18 for cluster 3.

• Acceptability of ICG-fluorescence implementation

  A questionnaire is administered to healthcare providers in each participating hospital during the 3rd month of Phase III, corresponding to month 12 for cluster 1, month 15 for cluster 2, and month 18 for cluster 3.

• Patient satisfaction with SLNB procedure

  Questionnaire administered within 1 week after surgery during all phases of the trial (from study start up to 18 months).

Study Arms (3)

Pre-implementation (99mTc only)

ACTIVE COMPARATOR

Participants undergo sentinel lymph node biopsy (SLNB) using the current standard of care: injection of radioisotope technetium-labeled (99mTc)-nanocolloid and preoperative lymphoscintigraphy, followed by radio-guided surgery with a gamma-detection probe.

Drug: Technetium (99mTc); Drug: Indocyanine Green; Procedure: Sentinel lymph node biopsy

Transition phase (99mTc + ICG)

EXPERIMENTAL

Participants receive preoperative injection of radioisotope technetium-labeled (99mTc)-nanocolloid and preoperative lymphoscintigraphy (without marking the location on the skin). Surgeons are blinded to preoperative lymphoscintigraphy results. After induction of general anesthesia, indocyanine green (ICG) is injected periareolar. Surgery is primarily guided by ICG fluorescence imaging to identify and remove the sentinel lymph node(s). Excised lymph nodes are then checked for 99mTc activity using a gamma-detection probe as a control. This phase is designed to allow surgeons to gain experience with the ICG technique while maintaining safety through parallel use of the established 99mTc method.

Drug: Indocyanine Green; Procedure: Sentinel lymph node biopsy

Post-implementation (ICG only)

ACTIVE COMPARATOR

Participants undergo SLNB using ICG only. ICG is injected periareolar after induction of general anesthesia and visualized intraoperatively with a fluorescence camera to guide excision of the sentinel lymph node(s).

Drug: Technetium (99mTc); Procedure: Sentinel lymph node biopsy

Interventions

Technetium (99mTc) DRUG

A radiopharmaceutical tracer consisting of technetium-99m (99mTc)-labelled nanocolloid used for sentinel lymph node mapping. In this study, 99mTc-nanocolloid is administered via periareolar injection with an activity of 40 MBq for the one-day protocol or 100 MBq for the two-day protocol, according to local hospital practice. Injection is performed either on the day of surgery or the afternoon before surgery. Preoperative lymphoscintigraphy is carried out to visualize lymphatic drainage. During surgery, a gamma-detection probe is used to locate and remove the sentinel lymph node(s) identified by 99mTc uptake.

Also known as: 99mTc, Technetium-99m labelled nanocolloid, Technetium-99, Technetium-99m, Tc99

Post-implementation (ICG only); Pre-implementation (99mTc only)

Indocyanine Green DRUG

Indocyanine Green (ICG) is a fluorescent dye used for intraoperative sentinel lymph node mapping. In this study, a total dose of 5 mg (2 mL) of ICG is administered via periareolar injection after induction of general anesthesia and prior to axillary incision. During surgery, near-infrared fluorescence imaging is used to visualize lymphatic drainage and identify the sentinel lymph node(s). The identified node(s) are surgically removed under fluorescence guidance. In the transition phase, fluorescence findings are cross-checked against 99mTc uptake to ensure accuracy and safety.

Also known as: ICG, fluorescence imaging

Pre-implementation (99mTc only); Transition phase (99mTc + ICG)

Sentinel lymph node biopsy PROCEDURE

Sentinel lymph node biopsy (SLNB) is a surgical procedure used to identify and remove the first lymph node(s) that drain lymph from a tumor area. In this study, SLNB is performed through a small axillary incision after mapping the sentinel lymph node(s) using either radioisotope technetium-labeled (99mTc)-nanocolloid, indocyanine green (ICG) fluorescence imaging, or a combination of both. The identified lymph node(s) are excised and sent for pathological examination to determine the presence of cancer cells. The procedure is carried out under general anesthesia as part of breast cancer surgery.

Also known as: Sentinel lymph node mapping, SLNB, SLN procedure, Sentinel lymph node procedure

Post-implementation (ICG only); Pre-implementation (99mTc only); Transition phase (99mTc + ICG)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years old.
• DCIS or invasive breast cancer, confirmed by biopsy
• Clinically node-negative, confirmed by preoperative axillary ultrasound
• Indication for breast cancer surgery with SLN procedure via axillar incision

You may not qualify if:

• Combined MARI procedure
• Known allergy for Indocyanine Green (ICG), intravenous contrast or iodine
• History of axillary lymph node dissection
• Hyperthyroidism or thyroid cancer
• Pregnancy or breast-feeding
• No written informed consent according to ICH/GCP and national regulations.

Sponsors & Collaborators

• Isabelle Henskens: lead
• Canisius-Wilhelmina Hospital: collaborator
• Spaarne Gasthuis: collaborator
• Noordwest Ziekenhuisgroep: collaborator
• Alrijne Hospital: collaborator
• Dijklander Ziekenhuis: collaborator
• Ziekenhuisgroep Twente: collaborator
• Diakonessenhuis, Utrecht: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (7)

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

RECRUITING

Ziekenhuisgroep Twente

Hengelo, Netherlands

RECRUITING

Spaarne Gasthuis

Hoofddorp, Netherlands

RECRUITING

Dijklander Ziekenhuis

Hoorn, Netherlands

RECRUITING

Alrijne Hospital

Leiden, Netherlands

RECRUITING

Canisius Wilhelmina Ziekenhuis

Nijmegen, Netherlands

RECRUITING

Diakonessenhuis

Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Lymphatic Metastasis

Interventions

Technetium; Technetium-99; Indocyanine Green; Optical Imaging; Sentinel Lymph Node Biopsy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Elements, Radioactive; Elements; Inorganic Chemicals; Metals, Heavy; Transition Elements; Radioisotopes; Isotopes; Metals; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Lymph Node Excision

Study Officials

• Annemiek Doeksen, MD, PhD

  St. Antonius Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isabelle Henskens, MD

CONTACT

+31883202902; i.henskens@antoniusziekenhuis.nl

Annemiek Doeksen, MD, PhD

CONTACT

+3188 320 29 00.; a.doeksen@antoniusziekenhuis.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Coordinating investigator

Model Details: This is a stepped-wedge cluster trial in which participating hospitals (clusters) are selected to represent different regions, settings, and sizes. The order in which hospitals transition is based on site readiness and in consultation with the participating centers. All hospitals begin with the current standard of care using radioisotope technetium-labeled (99mTc)-nanocolloid for sentinel lymph node biopsy (SLNB). At fixed intervals, clusters move to a transition phase using both 99mTc and indocyanine green (ICG), and then to ICG only. This sequential rollout creates an iterative learning cycle, allowing evaluation of the implementation process and refinements between phases. The total study duration is 18 months, with a fixed 6-month transition phase per cluster.

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 28, 2025
• Study Start: April 18, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

NL (7)