Identification of Sentinel Lymph Nodes Using Indocyanine Green in Breast Cancer Patients (INFLUENCE II)

Identification of Sentinel Lymph Nodes in Breast Cancer Patients Through Non-invasively Fluorescent Imaging Using Indocyanine Green: an International Multicenter Implementation Study.

This study aims to evaluate the (inter)national implementation of a new diagnostic method for sentinel lymph node (SLN) detection in breast cancer. While Technetium-99m (99mTc) is the current gold standard for SLN detection, it has drawbacks such as limited availability, logistical challenges, radiation exposure, and potential side effects. Extensive research indicates that Indocyanine Green (ICG) is an equally effective and potentially more practical alternative. Conducting this study will help accelerate the implementation of ICG in clinical practice.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Phase I: Technetium is administered as single tracer to identify the SLN (current standard).; Procedure: Phase II: SLN biopsy using double tracer technetium and ICG (learning curve); Procedure: Phase III: ICG is administered as single tracer to identify the SLN (alternative method).

Detailed Description

An important part of oncological treatment for breast cancer is determining the lymph node status. A commonly used method for this is the sentinel lymph node (SLN) procedure. Analysis of this node plays a key role in determining both treatment and prognosis.

Currently, the gold standard for SLN localization is the use of Technetium-99m (99mTc). However, this method has several disadvantages. Since not every hospital has a Nuclear Medicine Department, patients often need to be referred to another facility for 99mTc injection and nuclear imaging. This process can be burdensome for patients and poses logistical challenges when scheduling surgeries. In addition, the use of 99mTc involves exposure to radioactive material, and adverse effects such as allergic reactions have been reported. Recent studies have shown that the use of Indocyanine Green (ICG) is equally effective for sentinel lymph node localization as Technetium.

The aim of this study is to evaluate the national and international implementation process of a new diagnostic method for SLN detection.

• Study Type: Interventional
• Enrollment (Estimated): 493
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Peschiera del Garda, Italy
    • Ospedale Pederzoli
• Netherlands
  • 's-Hertogenbosch, Netherlands
    • Jeroen Bosch Ziekenhuis
  • Almere Stad, Netherlands
    • Flevoziekenhuis
  • Amsterdam, Netherlands
    • Antoni van Leeuwenhoek Ziekenhuis
  • Delft, Netherlands
    • Reinier de Graaf Gasthuis
  • Dirksland, Netherlands
    • Van Weel-Bethesda Ziekenhuis
  • Maastricht, Netherlands
    • Maastricht Universitair Medisch Centrum
  • Rotterdam, Netherlands
    • Erasmus Medisch Centrum
  • The Hague, Netherlands
    • HagaZiekenhuis
  • Uden, Netherlands
    • Bernhoven Ziekenhuis
  • Zwolle, Netherlands
    • Isala Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinically node-negative, DCIS or invasive breast cancer confirmed by biopsy
• Preoperative axillary ultrasound to confirm clinical node-negative status
• Indication for breast cancer surgery with SLNB via axillar incision
• Written informed consent according to ICH/GCP and national regulations.

Exclusion Criteria:

• Patients < 18 years old.
• Indication for breast cancer surgery with SLNB via mastectomy incision
• Combined MARI procedure
• Known allergy for Indocyanine Green (ICG) or intravenous contrast or iodine
• History of axillary lymph node dissection
• Hyperthyroidism or thyroid cancer
• Pregnancy or breast-feeding
• Psychological, familial, sociological or geographical factors that could potentially hamper compliance with the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Phase I: pre-implemtation phase; SLN biopsy using single tracer techentium (current standard)	Procedure: Phase I: Technetium is administered as single tracer to identify the SLN (current standard).; During this phase, surgeons will use technetium to identify the SLN as this is the current standard of care. This phase will serve as a control group.
Other: Phase II: transition phase; SLN biopsy using double tracer technetium and ICG (learning curve)	Procedure: Phase II: SLN biopsy using double tracer technetium and ICG (learning curve); During this phase, surgeons will primarily use ICG to identify the sentinel lymph node (SLN), while technetium will serve as a control. This approach allows surgeons to gain proficiency with ICG-guided SLN biopsy and safely advance through the learning curve.
Other: Phase III: post-implementation phase; SLN biopsy using single tracer ICG (alternative method)	Procedure: Phase III: ICG is administered as single tracer to identify the SLN (alternative method).; During this phase, surgeons will use ICG as a singe tracer to identify the SLN.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identifaction rate	Identification rate is defined as the proportion of patients in whom lymph nodes were identified with the gamma-probe using technetium or the fluorescent signal of ICG.	Perioperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of lymph nodes identified	This indicates the total number of lymph nodes identified with ICG or technetium.	Perioperatively
Percentage of SLNs identified per tracer	Percentage of SLNs that had technetium uptake / were fluorescent.	Perioperatively
Pathology assesment per SLN	The pathology of the identified SLN during surgery	Perioperatively
Detection time	Time in minutes to excise the SLN, measured from start of SLN procedure until detection of the first SLN.	Intraoperatively
Complications	Complications including (wound)infection, bleeding, seroma, and mild allergic reaction.	From the time of the SLN procedure up until three weeks of follow-up.
Adverse events	Number of adverse events attributable to technetium or ICG.	Monitored during study period until one year of follow-up
Locoregional recurrence at 1 year follow-up		Until the end of the study (after 1 year of follow-up)
Surgeon's expectations regarding ICG	Expectations of the participating surgeons regarding the use of ICG for SLN procedure using a study-specific survey with open-ended questions and multiple choice items.	Pre-implementation (prior to the transion phase)
Surgeons' experiences regarding ICG	Experiences of the participating surgeons regarding the use of ICG for SLN procedure using a study-specific survey with open-ended questions and multiple choice items.	Up to 12 months after transition to ICG as single tracer
Learning curve per surgeon	The learning curve process will be expressed by visualizing inter-surgeon variability in the number of procedures required to achieve proficiency portrayed in a scatterplot.	From each surgeon's first procedure using the double tracer method (technetium and ICG) through completion of the transition phase, assessed over up to 12 months.

Collaborators and Investigators

• Sponsor: St. Antonius Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2023
• Primary Completion (Actual): October 30, 2025
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: December 20, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: indocyanine green; ICG; implementation; fluorescence; sentinel lymph node mapping; sentinel lymph node biopsy; sentinel lymph node procedure
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: NL79223.100.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No