Finding Sentinel Lymph Nodes During Mastectomy Using Indocyanine Green (INIGMA Study)

Isabelle Henskens

Status: Enrolling

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

Treatments: Other: Indocyanine green (ICG)-fluorescence guided sentinel lymph node biopsy

Study type: Interventional

Funder types: Other

Identifiers

NCT07362485

NL80591.100.22

Details and patient eligibility

About

This pilot study evaluates the diagnostic value of indocyanine green (ICG) fluorescence for sentinel lymph node biopsy (SLNB) performed through the mastectomy incision in breast cancer patients.

Women with clinically node-negative, invasive T1-T3 breast cancer undergoing mastectomy with SLNB at St. Antonius or Isala Hospital will be included. All patients receive standard 99mTc injection preoperatively, followed by 5 mg (2mL) ICG injection after anesthesia. The axilla will be explored for fluorescent lymph nodes via the mastectomy incision, avoiding a separate axillary incision.

Primary outcome: ICG detection rate for SLN identification via the mastectomy incision.

Secondary outcomes: Comparison with 99mTc detection, number of nodes identified, concordance between methods, pathology differences, detection time, and complications.

ICG is safe, non-ionizing, and causes no extra discomfort or visits. Risks and burden are minimal.

Full description

Background:

Identifying lymphatic metastases is an important prognostic factor in the survival rate of breast cancer and the presence of lymphatic metastases carries consequences for further treatment. Results the non-inferiority INFLUENCE study and previous literature, led to the implementation of ICG-guided SLNBs via axillary incision as standard of care at the St. Antonius Hospital. The diagnostic performance of ICG-fluorescence for SNLBs using the mastectomy incision has not been described yet. Surgeons may perform SLNBs using the same incision as the mastectomy, rather than using an additional axillary incision. In such setting, extended operating distance and visualization with an improper angle might introduce challenges to identify the SLN by tracking lymphatic vessels into the axilla.

Objective:

This pilot study aims to identify the diagnostic value of indocyanine green (ICG) fluorescence imaging for SLNBs via the mastectomy incision.

Study design:

This is a multicenter, cross-sectional pilot study identifying the diagnostic value of indocyanine green (ICG) fluorescence imaging for SLN mapping via the mastectomy incision (different surgical approach).

Study population:

Women with breast cancer who are admitted to the St. Antonius Hospital or Isala Hospital. Inclusion criteria include clinically nodenegative, invasive T1-T3 breast cancer conformed by biopsy, preoperative axillary ultrasound to confirm clinical node-negative status and indication for mastectomy with SLN procedure.

Intervention:

All included patients will receive standard of care implying 99mTc injection the day before surgery. Consequently, 5 mg (2 ml) ICG will be injected periareolar after administration of general anaesthesia and before incision. The lateral edge of the standard mastectomy incision will be used to explore the axilla for ICG fluorescent lymph nodes to avoid a separate axillary incision. Then the excised nodes are tested for 99mTc activity with the standard gamma detecting probe as control. Lastly, the axilla will be explored with the standard gamma-probe for residual lymph nodes, and by common sight and palpation as a control.

Outcomes:

Primary: to assess the detection rate of the ICG method to identify the SLN via a mastectomy incision.

Secondary:

• The detection rate of 99mTc
• The difference in detection rate between ICG and 99mTc
• The median number of SLN identified with ICG and the standard 99mTc
• Percentage of SLNs that is fluorescent, but not positive for 99mTc
• Percentage of SLNs that are not fluorescent but positive for 99mTc
• The difference in pathology of the SLN found by ICG and 99mTc, including the difference between micro- and macro metastases (Mic and Mac resp.) and isolated tumor cells (ITCs)
• Detection time for the use of ICG to detect the SLN, defined as time between skin incision and SLN resection in minutes
• Complications, including wound infection, bleeding and lymphedema, of the combination of the ICG method and the standard 99mTc method to identify the SLN in mastectomies
• The number of serious adverse events from the combination of ICG and 99mTc

Risks and burden:

Consenting patients will not need to do anything extra than the standard of care outside signing the informed consent. Administration of ICG will be done while under general anaesthesia, so patients will not experience extra discomfort, neither do they need extra site visits as the follow-up will be done during the standard follow-up appointment. ICG is safe to use: it is nonionizing and knows little to no complications and adverse events. Considering the cut-off of 2 additional nodes, the preferable topographic location of these nodes and the clinical experience with additional lymph node sampling, no increase in risk of surgical morbidity is expected. Patients might benefit from the intervention as ICG can increase the identification rate of the sentinel lymph node procedure and might even replace 99mTc for SLN mapping. Thus, both risks and burden are minimal.

Enrollment: 90 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Clinically node-negative, DCIS, invasive T1- T3 breast cancer confirmed by biopsy.
• Preoperative axillary ultrasound to confirm clinical node-negative status.
• Indication (or preference) for mastectomy and simultaneous SLN procedure.
• Written informed consent according to ICH/GCP and national regulations.

Exclusion criteria

• Patients < 18 years old
• Breast conserving surgery
• Direct reconstruction (with autologous tissue or implant)
• Known allergy for indocyanine green (ICG) or radioisotope technetium (99mTc), intravenous contrast or iodine
• Other concurrent solid tumour
• Hyperthyroidism or thyroid cancer
• Pregnancy or breast feeding
• Psychological, familial, sociological or geographical factors that could potentially hamper compliance with the study protocol

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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90 participants in 1 patient group

ICG-fluorescence imaging with 99mTc control for SLNB

Experimental group

Description:

This experimental arm involves participants receiving indocyanine green (ICG) fluorescence imaging as the primary method for sentinel lymph node biopsy (SLNB), with 99mTc-nanocolloid serving as the within-patient control. Both methods are applied during the same surgical procedure. This design allows each participant to serve as their own control for comparing the diagnostic perfomance of both techniques directly in indentifying sentinel lymph nodes via mastectomy incision.

Treatment:

Other: Indocyanine green (ICG)-fluorescence guided sentinel lymph node biopsy