Device Validation of Augmented-Reality ICG Fluorescence Imaging for Sentinel Lymph Node Detection in Breast Cancer

Validation of Augmented-Reality/Virtual-Reality Goggle-Based Near-Infrared Fluorescence Imaging for Sentinel Lymph Node Detection in Patients With Breast Cancer

This study evaluates how accurately augmented-reality goggles with indocyanine green (ICG) near-infrared fluorescence can identify sentinel (first-draining) lymph nodes during breast cancer surgery. The goggles and ICG signal are used to mark candidate sentinel nodes, and an additional observer may record near-infrared images during the operation for device-performance assessment. These imaging findings do not change the surgical procedure. The candidate nodes and all removed tissue are examined by histopathology, which serves as the reference standard. Two hundred patients undergoing breast cancer surgery will take part. The study measures how well the goggle-based imaging detects nodes that contain cancer, compared with final pathology.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Breast Neoplasms; Lymphatic Metastasis; Sentinel Lymph Node
• Intervention / Treatment: Device: AR-ICG near-infrared fluorescence imaging

Detailed Description

This is a prospective observational device-validation study in patients undergoing breast cancer surgery with axillary evaluation. Augmented-reality goggle-based near-infrared fluorescence imaging with ICG is used to visualize and mark candidate sentinel lymph nodes. Intraoperative near-infrared imaging may be performed by an observer who is not the operating surgeon, solely to assess device performance; observer findings are not communicated to the operating surgeon before wound closure and do not influence the operation. All marked nodes and removed tissue undergo histopathology, which serves as the blinded reference standard. Device performance is assessed on consecutive eligible patients within defined enrollment windows; for each near-infrared imaging device, sensitivity, specificity, positive and negative predictive value, and node-level ROC analysis are estimated against final histopathology, with confidence intervals accounting for clustering of nodes within patients. The study is non-interventional: the imaging does not alter surgical management.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Borislav Kondov, MD; Phone Number: +38972539003; Email: borislav.kondov@medf.ukim.edu.mk
• Study Contact Backup: Name: Magdalena Bogdanovska Todorovska, MD; Phone Number: +389709602221; Email: magdalena.todorovska@medf.ukim.edu.mk

Study Locations

• North Macedonia
  • Skopje, North Macedonia, 1000
    • University Clinic for Thoracic and Vascular Surgery, Faculty of Medicine, UKIM
    • Contact: Borislav Kondov, MD; Phone Number: +38972539003; Email: borislav.kondov@medf.ukim.edu.mk

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with histologically proven breast cancer undergoing surgery with axillary lymph node evaluation at the participating center, enrolled consecutively.

Description

Inclusion Criteria:

• Histologically proven breast cancer
• Age 18 years or older
• Undergoing breast cancer surgery with sentinel lymph node evaluation and/or axillary lymph node dissection
• Provides written informed consent

Exclusion Criteria:

• Pregnancy
• Neoadjuvant chemotherapy
• Prior breast surgery
• Iodine or seafood allergy
• Indocyanine green (ICG) allergy
• Declines or is unable to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Breast cancer patients undergoing surgery with AR-ICG node imaging; Patients undergoing breast cancer surgery in whom AR-ICG goggle-based near-infrared imaging is used to mark candidate sentinel nodes, with optional observer near-infrared imaging for device-performance assessment; histopathology is the reference standard.

Device: AR-ICG near-infrared fluorescence imaging; Augmented-reality goggle-based near-infrared fluorescence imaging with indocyanine green (ICG), used to visualize and mark candidate sentinel lymph nodes during breast cancer surgery. Intraoperative near-infrared imaging may also be recorded by an observer for device-performance assessment. Imaging does not alter surgical management; histopathology serves as the reference standard.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Node-level diagnostic accuracy of AR-ICG fluorescence imaging versus histopathology	Sensitivity, specificity, positive and negative predictive value, and area under the ROC curve for goggle-based near-infrared fluorescence detection of tumor-positive lymph nodes, using final histopathology as the reference standard, with confidence intervals accounting for clustering of nodes within patients.	From surgery to final histopathology (up to ~2 weeks after surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-level sentinel-node detection rate	Proportion of patients in whom at least one sentinel lymph node is identified by AR-ICG near-infrared fluorescence imaging.	Final histopathology (up to approximately 2 weeks after surgery)
Concordance of device-marked nodes with histopathology	Agreement between lymph nodes marked by AR-ICG fluorescence imaging and nodal status confirmed on final histopathology.	Final histopathology (up to approximately 2 weeks after surgery)
Per-device diagnostic performance across near-infrared imaging systems	Sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve estimated separately for each near-infrared imaging device evaluated, using final histopathology as the reference standard, on consecutive eligible patients within defined enrollment windows.	Through study completion (up to approximately 24 months)
False-negative rate of AR-ICG fluorescence node detection	Proportion of pathology-confirmed tumor-positive lymph nodes not identified as fluorescent by AR-ICG imaging.	Final histopathology (up to approximately 2 weeks after surgery)
Number of candidate sentinel nodes identified per patient	Number of candidate sentinel lymph nodes marked by AR-ICG fluorescence imaging per patient (count).	Intraoperative (day of surgery)

Collaborators and Investigators

• Sponsor: Ss. Cyril and Methodius University of Skopje
• Collaborators: University of Illinois at Urbana-Champaign

Publications and helpful links

General Publications

• Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, Ollila DW, Hansen NM, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Morrow M. Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017 Sep 12;318(10):918-926. doi: 10.1001/jama.2017.11470.
• Xiong X, Zheng LW, Ding Y, Chen YF, Cai YW, Wang LP, Huang L, Liu CC, Shao ZM, Yu KD. Breast cancer: pathogenesis and treatments. Signal Transduct Target Ther. 2025 Feb 19;10(1):49. doi: 10.1038/s41392-024-02108-4.
• Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014 Nov;15(12):1303-10. doi: 10.1016/S1470-2045(14)70460-7. Epub 2014 Oct 15.
• de Boniface J, Filtenborg Tvedskov T, Ryden L, Szulkin R, Reimer T, Kuhn T, Kontos M, Gentilini OD, Olofsson Bagge R, Sund M, Lundstedt D, Appelgren M, Ahlgren J, Norenstedt S, Celebioglu F, Sackey H, Scheel Andersen I, Hoyer U, Nyman PF, Vikhe Patil E, Wieslander E, Dahl Nissen H, Alkner S, Andersson Y, Offersen BV, Bergkvist L, Frisell J, Christiansen P; SENOMAC Trialists' Group; SENOMAC Trialists' Group. Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases. N Engl J Med. 2024 Apr 4;390(13):1163-1175. doi: 10.1056/NEJMoa2313487.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 28, 2026
• First Submitted That Met QC Criteria: June 28, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 28, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: diagnostic accuracy; augmented reality; indocyanine green; sentinel lymph node biopsy; near-infrared fluorescence; medical device validation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Skin Diseases; Breast Diseases; Neoplasm Metastasis; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Breast Neoplasms; Lymphatic Metastasis
• Other Study ID Numbers: UKIM-AR-ICG-BREAST-VALID-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a single-center observational device-validation study. Individual participant data are not planned to be shared. De-identified data may be made available from the principal investigator on reasonable request, subject to institutional approval.

Drug and device information, study documents

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