Sentinel Lymph Node Biopsy for Breast Cancer

(SHINE Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University Health Network, Toronto

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

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a prospective, open-label, within-patient clinical trial to determine the accuracy of Indocyanine green (ICG) guided sentinel lymph node biopsy (SLNB) compared to the standard dual-tracer SLNB in breast cancer patients who have had chemotherapy as a first treatment using a non-inferiority design. Patients with operable breast cancer treated with chemotherapy and eligible for SLNB will be included in the study. During surgery, ICG will be injected and used to identify fluorescent sentinel nodes using a hand-held imaging camera; radiotracer and blue dye will also be used as per standard protocols. Intraoperative and clinicopathologic outcomes such as complications, characteristics of nodes, false negative rates and feasibility will be assessed. Patients will be asked to complete standardized patient reported outcome questionnaires (Breast-Q, FACT-B+4, VAS) to define the patient experience with this novel technique.

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 data supports the effectiveness of the drug Indocyanine Green Guided Sentinel Lymph Node Biopsy (ICG-SLNB) for breast cancer?

Research shows that using indocyanine green (ICG) as a tracer for sentinel lymph node biopsy in breast cancer is effective, with detection rates similar to or better than traditional methods, without the risks of radioactivity. ^{1 2 3 4 5}

Is indocyanine green (ICG) safe for use in sentinel lymph node biopsy for breast cancer?

Indocyanine green (ICG) has been used as a tracer in sentinel lymph node biopsy for breast cancer and other conditions, with studies indicating it is generally safe for human use. Some research has focused on its safety and feasibility, showing it can be used without the risks associated with radioactive tracers. ^{3 5 6 7 8}

How is ICG guided sentinel lymph node biopsy different from other treatments for breast cancer?

ICG guided sentinel lymph node biopsy is unique because it uses indocyanine green (ICG), a dye visible in infrared light, to help identify sentinel lymph nodes during surgery. This method allows for transcutaneous (through the skin) visualization of lymphatic vessels and intraoperative identification of sentinel lymph nodes, potentially offering a less invasive and more precise alternative to traditional methods that use radioactive substances and blue dye. ^{3 4 8 9 10}

Research Team

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• ICG guided sentinel lymph node biopsy (Procedure)

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.

Participant Groups

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 China, India for the following indications:

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+

Dr. Brad Wouters

University Health Network, Toronto

Chief Medical Officer since 2020

MD from University of Toronto

Dr. Kevin Smith

University Health Network, Toronto

Chief Executive Officer since 2018

Professor at McMaster University and University of Toronto

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. Switzerland 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical utility of the additional use of blue dye for indocyanine green for sentinel node biopsy in breast cancer. [2022]

3. England 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescence. [2022]

5. China (Republic : 1949- ) 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Short-term and long-term outcomes of indocyanine green for sentinel lymph node biopsy in early-stage breast cancer. [2022]

7. United States 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. [2022]

8. United States 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. [2015]

9. Poland pubmed.ncbi.nlm.nih.gov

Sentinel node biopsy in breast cancer using infrared laser system first experience with PDE camera. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

ICG fluorescence-guided sentinel node biopsy for axillary nodal staging in breast cancer. [2022]