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

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.

• Identification rate of sentinel lymph nodes using 99mTc [Срок оценки: During the surgical procedure (from skin incision to completion of sentinel lymph node resection)]
• Difference in sentinel lymph node detection rate between ICG and 99mTc [Срок оценки: During the surgical procedure (from skin incision to completion of sentinel lymph node resection)]
• Number of sentinel lymph nodes identified per participant by ICG and 99mTc [Срок оценки: During the surgical procedure (from skin incision to completion of sentinel lymph node resection)]
• Proportion of participants with fluorescent sentinel lymph nodes among those identified by 99mTc [Срок оценки: During the surgical procedure (from skin incision to completion of sentinel lymph node resection)]
• Fluorescent sentinel lymph nodes not positive for 99mTc [Срок оценки: During the surgical procedure (from skin incision to completion of sentinel lymph node resection)]
• Sentinel lymph nodes positive for 99mTc but not fluorescent [Срок оценки: During the surgical procedure (from skin incision to completion of sentinel lymph node resection)]
• Pathological status of sentinel lymph nodes identified by ICG and 99mTc [Срок оценки: From surgical resection of sentinel lymph nodes until completion of histopathological assessment, assessed within approximately 3 weeks after surgery]
• Detection time for sentinel lymph node identification using ICG [Срок оценки: During the surgical procedure (from skin incision to sentinel lymph node resection)]
• Procedure-related complications associated with ICG and 99mTc [Срок оценки: From surgery up to 2 months postoperatively]
• Serious adverse events related to ICG and 99mTc [Срок оценки: From surgery up to 2 months postoperatively]