Sentinel Lymph Node Biopsy for Breast Cancer

(SHINE Trial)

Overseen By Karineh Kazazian, MD PhD FRCSC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Significant comorbidities, T4/inflammatory, node positive, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to determine if breast cancer has spread to nearby lymph nodes after chemotherapy. It compares the dye Indocyanine green (ICG) with the usual method that uses two different tracers. The researchers aim to determine if ICG is equally effective in identifying cancerous nodes. Ideal participants have operable breast cancer, have completed chemotherapy, and are scheduled for a sentinel lymph node biopsy (ICG-guided sentinel lymph node biopsy). Participants will provide feedback on their experience through simple questionnaires. As an unphased trial, this study allows participants to contribute to innovative research that could enhance future breast cancer diagnostics.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this technique is safe for breast cancer patients?

Research has shown that using indocyanine green (ICG) to locate sentinel lymph nodes in breast cancer surgery is generally safe. In one study, ICG mixed with a blue dye proved safe and effective for patients with early-stage breast cancer. Another study demonstrated that ICG helped doctors find lymph nodes more quickly and accurately than older methods. This suggests that ICG can be a reliable tool for doctors during surgery. Overall, studies suggest that ICG is well-tolerated and does not cause serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ICG-guided sentinel lymph node biopsy (SLNB) because it combines a novel fluorescent dye, indocyanine green (ICG), with traditional tracers like blue dye and Tc-99m. This method aims to improve the precision of detecting sentinel lymph nodes during surgery. Unlike standard dual-tracer SLNB, which typically uses only two tracers, the addition of ICG offers the potential for more accurate localization of lymph nodes, particularly in patients treated with neoadjuvant chemotherapy. Enhanced accuracy in identifying sentinel lymph nodes could lead to better surgical outcomes and less invasive treatment for breast cancer patients.

What evidence suggests that ICG guided sentinel lymph node biopsy is effective for breast cancer?

Research has shown that indocyanine green (ICG) effectively identifies sentinel lymph nodes in breast cancer patients. In this trial, participants will undergo ICG-guided sentinel lymph node biopsy (ICG-SLNB) to evaluate its accuracy against standard dual-tracer SLNB. Studies indicate that ICG can successfully locate these critical nodes, even in patients who have undergone chemotherapy. It proves to be as effective as, and sometimes superior to, traditional methods like blue dye and radiotracers. In some cases, ICG may detect more sentinel nodes. Patients undergoing this procedure might experience fewer complications and more accurate identification of nodes requiring removal. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

The SHINE trial is for adults aged 18-80 with Stage I-III invasive breast cancer who've had chemo and are set for a sentinel lymph node biopsy (SLNB). They must be in good physical condition, not allergic to ICG/iodine, able to consent, and literate in English. It's not for those with severe health issues, advanced breast cancer stages unsuitable for SLNB, or past surgery/radiotherapy on the affected area.

Inclusion Criteria

I have stage I-III breast cancer, had chemotherapy, and will have a sentinel lymph node biopsy.

I can do all my daily activities without help.

English literacy

Exclusion Criteria

My breast cancer is at an advanced stage or has spread to nearby lymph nodes.

I have had surgery or radiation on the same side breast or armpit before.

You have serious medical conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Patients receive chemotherapy as the first treatment before surgery

Varies based on individual treatment plans

Surgery and Sentinel Lymph Node Biopsy

ICG is injected to identify fluorescent sentinel nodes during surgery; radiotracer and blue dye are also used

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery, including patient-reported outcomes

12 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• ICG guided sentinel lymph node biopsy

Trial Overview This study tests if using Indocyanine green (ICG) to guide SLNB during surgery is as accurate as the standard method using blue dye and radiotracer. Patients will have both techniques used during their operation to compare results. The trial also looks at patient comfort and surgical outcomes through questionnaires.

How Is the Trial Designed?

Group I: ICG-SLNB Experimental Treatment 1 Intervention

This is a prospective within-patient clinical study to assess the accuracy of ICG SLNB compared to standard dual-tracer SLNB in breast cancer patients treated with neoadjuvant chemotherapy. For SLNB, triple localization of the sentinel lymph nodes using blue dye, Tc-99m and ICG will be utilized in each patient.

ICG guided sentinel lymph node biopsy is already approved in European Union, United States, China, India for the following indications:

Approved in European Union as Indocyanine Green for:

• Diagnostic imaging agent for sentinel lymph node detection in breast cancer

Approved in United States as Indocyanine Green for:

• Diagnostic imaging agent for sentinel lymph node detection in breast cancer

Approved in China as Indocyanine Green for:

• Diagnostic imaging agent for sentinel lymph node detection in breast cancer

Approved in India as Indocyanine Green for:

• Diagnostic imaging agent for sentinel lymph node detection in breast cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study of 1414 patients undergoing sentinel lymph node biopsy for endometrial cancer, there were no reported anaphylactic reactions to indocyanine green (ICG), even among those with a history of iodine or contrast allergies.

The incidence of adverse reactions was low, with only 3 patients experiencing potentially allergic reactions, suggesting that ICG is safe for use in this context, especially when premedication with corticosteroids is applied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel lymph node biopsy in patients with endometrial cancer and an indocyanine green or iodinated contrast reaction - A proposed management algorithm. Zammarrelli, WA., Afonso, AM., Broach, V., et al.[2022]

Indocyanine green (ICG) fluorescence imaging demonstrated a high detection rate of 97.7% for sentinel lymph nodes (SLN) in a study of 43 women with breast cancer, indicating its effectiveness as a new method for SLN biopsy.

The technique showed a sensitivity of 94.4% for identifying metastatic involvement in SLNs, with only one false-negative case, and no axillary recurrences reported after a median follow-up of 4.7 years, suggesting its safety and reliability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ICG fluorescence-guided sentinel node biopsy for axillary nodal staging in breast cancer. Hirche, C., Murawa, D., Mohr, Z., et al.[2022]

In a study of 86 breast cancer patients, combining near-infrared ICG fluorescence with blue dye for sentinel lymph node biopsy (SLNB) did not significantly increase the identification rate of sentinel lymph nodes (98.8% vs. 93%), but it did reduce the false-negative rate from 12% to 4%.

The combination of ICG and blue dye is beneficial for improving diagnostic accuracy in SLNB, making it a suitable alternative for hospitals lacking access to traditional radiation-based detection methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the benefit of using blue dye in addition to indocyanine green fluorescence for sentinel lymph node biopsy in patients with breast cancer. Guo, W., Zhang, L., Ji, J., et al.[2021]

In a study of 59 patients undergoing sentinel lymph node biopsy (SLNB) for breast cancer and skin melanoma, the use of indocyanine green (ICG) and ICG conjugated to human serum albumin (ICG:HSA) showed low long-term morbidity, with only 6.4% of patients experiencing complications after about one year.

While the procedure was deemed safe, some patients did experience skin discoloration and mild lymphedema, suggesting that while ICG is a promising alternative to traditional dyes, careful monitoring for these side effects is still necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year postoperative morbidity associated with near-infrared-guided indocyanine green (ICG) or ICG in conjugation with human serum albumin (ICG:HSA) sentinel lymph node biopsy. Murawa, D., Polom, K., Murawa, P.[2015]

The use of indocyanine green (ICG) as a fluorescent tracer for sentinel lymph node biopsy (SLNB) in breast cancer patients resulted in a 100% sensitivity rate for detecting sentinel lymph nodes, demonstrating its effectiveness.

This study, involving 184 patients, confirms that ICG is a safe alternative to traditional radioisotope methods, reducing risks associated with radioactivity and potentially lowering costs and resource use in the surgical process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of indocyanine green as the only tracer for the identification of the sentinel lymph node in breast cancer: safety and feasibility. Pellini, F., Bertoldi, L., Deguidi, G., et al.[2022]

In a study involving 127 patients with primary breast cancer, combining indocyanine green (ICG) with methylene blue dye during sentinel lymph node biopsy (SLNB) significantly increased the average number of sentinel lymph nodes removed (3.8 vs. 2.7) and reduced the detection time for each node (3.91 vs. 5.65 minutes).

The identification rates of sentinel lymph nodes were similar between the two methods (95.2% for ICG alone vs. 98.5% for ICG with blue dye), and no severe adverse reactions or complications were reported, indicating that the combination is safe and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of the additional use of blue dye for indocyanine green for sentinel node biopsy in breast cancer. Ji, Y., Luo, N., Jiang, Y., et al.[2022]

Fluorescence detection of sentinel lymph nodes (SLNs) using indocyanine green (ICG) was highly effective, identifying SLNs in 29 out of 30 women with breast cancer, resulting in a detection rate of 97%.

The sensitivity of ICG for detecting metastatic SLNs was 90%, which is comparable to traditional methods, demonstrating that ICG can effectively combine the benefits of both radioisotope and blue dye techniques for lymphatic mapping.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescence. Murawa, D., Hirche, C., Dresel, S., et al.[2022]

Indocyanine green (ICG) demonstrated a 99% identification rate for sentinel lymph nodes (SLN) in breast cancer patients, which is significantly higher than the 92.8% rate achieved with methylene blue (MB), indicating its superior efficacy as a tracer.

The study, involving 194 patients over a median follow-up of 67 months, found no allergic reactions or permanent skin staining related to ICG, suggesting it is a safe alternative to traditional SLN tracers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term and long-term outcomes of indocyanine green for sentinel lymph node biopsy in early-stage breast cancer. Hua, B., Li, Y., Yang, X., et al.[2022]

Indocyanine green (ICG) used in sentinel node biopsy (SNB) for breast cancer patients demonstrated a 100% sensitivity in detecting the lymphatic network, indicating its effectiveness as a tracer.

The study suggests that ICG could be a promising alternative to the standard tracer nanocoll, potentially enhancing the diagnostic capabilities in mapping lymphatic networks, despite some drawbacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel node biopsy in breast cancer using infrared laser system first experience with PDE camera. Polom, K., Murawa, D., Michalak, M., et al.[2021]

In a study of 240 women with early breast cancer, indocyanine green (ICG) achieved a 100% detection rate for sentinel lymph nodes, outperforming blue dye, which had a 97.5% detection rate.

ICG is a promising alternative to blue dye for sentinel lymph node biopsy, offering similar efficacy without the need for radioactive isotopes, making it easier to learn and more cost-effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Prospective Non-Inferiority Trial of Sentinel Lymph Node Biopsy in Early Breast Cancer: Blue Dye Compared with Indocyanine Green Fluorescence Tracer. Coibion, M., Olivier, F., Courtois, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11953180/

Sentinel lymph node biopsy in breast cancer ICG fluorescence-guided SLNB proved to be a feasible and promising method for SNs identification among BC patients after NAC.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1015958425001319

Comparative efficacy of indocyanine green and Tc-99m for ... This retrospective study aimed to compare the sensitivity of sentinel lymph node (SLN) detection using indocyanine green (ICG), Technetium-99 (Tc-99m), and ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/wjo2.197

Indocyanine green fluorescence‐guided sentinel lymph ... ICG-guided SLNB procedures are feasible and effective in the context of HNCs. The technique offers potentially higher SLN detection rates and shows promise.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07146295

Implementation of Indocyanine Green to Identify Sentinel ... Surgery is primarily guided by ICG fluorescence imaging to identify and remove the sentinel lymph node(s). Excised lymph nodes are then checked ...

5. mdpi.com mdpi.com/2072-6694/15/24/5755

An Updated Review on the Emerging Role of Indocyanine ... This article is an updated overview of somerecent studies that compared ICG with BD and/or RI regarding their accuracy and effectiveness during SLNB for breast ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1526820923000320

Indocyanine Green and Methylene Blue Dye Guided ... Indocyanine green combined with methylene blue dual-tracer method is safe and effective in sentinel lymph node biopsy in patients with early breast cancer.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06085274

Sentinel lympH Node Biopsy With Indocyanine Green in ... This is a prospective, open-label, within-patient clinical trial to determine the accuracy of Indocyanine green (ICG) guided sentinel lymph node biopsy (SLNB) ...

8. abs.amegroups.org abs.amegroups.org/article/view/6004/html

Use of indocyanine green in detection of breast axillary ... Sentinel lymph node detection with ICG yielded a higher detection rate in comparison to isosulfan blue dye. ICG allows decreased time to reach nodes and does ...