ICG Dye to Reduce Fistulas After Throat Cancer Surgery

Overseen By Douglas Chepeha, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Immune suppressants

Disqualifiers: Total laryngopharyngectomy, Hematologic malignancy, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

70 Participants Needed

Trial Summary

What is the purpose of this trial?

A laryngectomy involves removing the voice box from the throat. After the voice box has been removed from the throat, the surgeon sews the throat closed. Sometimes part of the throat does not heal and saliva runs out of the throat. This is called a fistula. When a fistula happens, healing takes longer and patients will have to wait to eat and start speaking. The test in this research project is called ICG scan (indocyanine green) and tells the surgeon how much blood is flowing to different parts of the throat. If the test shows that there are parts of your throat that have low blood flow, which will delay healing. Only half of the patients in the study will get the ICG scan. This is so the patients who had the ICG scan can be compared to the patients that did not have the ICG scan to determine if the ICG scan really helps decrease fistulas.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immune suppression medications, you cannot participate in the trial.

What data supports the effectiveness of the treatment ICG dye in reducing fistulas after throat cancer surgery?

Research shows that Indocyanine Green (ICG) is effective in improving surgical outcomes by providing better visualization during surgery. It has been used successfully in other types of surgeries, like colorectal and breast cancer surgeries, to help surgeons see important structures and reduce complications, which suggests it might also help in throat cancer surgeries. ^{1 2 3 4 5}

Is Indocyanine Green (ICG) dye safe for use in humans?

Indocyanine Green (ICG) dye has been used in medicine since the 1950s for various applications, including heart, eye, and brain surgeries. While it has a narrow safety profile, meaning it must be used carefully, it is generally considered safe when used properly. However, there have been reports of vision problems after its use in eye surgeries, so its safety can depend on the specific medical procedure. ^{3 4 6 7 8}

How does the treatment using ICG dye differ from other treatments for reducing fistulas after throat cancer surgery?

The use of ICG dye in this treatment is unique because it involves a special dye that lights up under near-infrared light, helping doctors see blood flow and tissue health during surgery. This can help reduce the risk of fistulas (abnormal connections between organs) by ensuring better surgical precision and tissue healing, which is not a standard approach in throat cancer surgeries. ^{3 4 9 10 11}

Eligibility Criteria

This trial is for adults over 18 who need a salvage laryngectomy after radiation or chemoradiation. They must be in fair health (ECOG 0-2), have a throat condition suitable for ICG imaging, and agree to follow the study's procedures. It's not for those with blood cancers, iodine allergy, high thyroid-stimulating hormone levels, certain types of throat surgery history, on immune suppressants, pregnant women, or very underweight individuals.

Inclusion Criteria

I am able to care for myself and perform daily activities.

Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

The expected pharyngeal defect must be conducive to imaging with the ICG

Exclusion Criteria

Pregnancy

TSH greater than 8

Allergy to Iodine

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Treatment

Participants undergo salvage laryngectomy with or without ICG imaging to assess tissue perfusion and guide mucosal debridement

1 week

1 visit (in-person)

Post-Surgical Monitoring

Participants are monitored for surgical complications and initial recovery post-surgery

1 week after hospital discharge

Follow-up

Participants are monitored for disease status, laryngeal rehabilitation, and speech and swallowing ability

12 months

Visits at week 1, 3 months, 6 months, and 12 months

Treatment Details

Interventions

• ICG dye

Trial Overview The trial tests if using an ICG scan during surgery can reduce fistula rates by showing blood flow in the throat. Patients are randomly chosen to either receive this scan or not during their laryngectomy so that outcomes can be compared between both groups.

Participant Groups

Group I: ICG Experimental Treatment 1 Intervention

This study will use intraoperative ICG imaging to assess recipient pharyngeal tissue perfusion. The ICG is the vascular contrast agent and the SPY Elite is the imaging device. 3mL of ICG will be injected using a peripheral IV access, followed by a 10mL saline flush. The pharyngeal mucosa will be imaged to quantify the tissue perfusion. Poorly perfused areas (less than 25%) will be debrided

Group II: Control Active Control 1 Intervention

Patients assigned to the observation (control) group will undergo standard of care reconstruction of mucosa

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

Findings from Research

Indocyanine green (ICG) imaging for head and neck cancer surgery showed a high sensitivity of 91.7% and a tumor-to-background ratio of 1.56, indicating its effectiveness in distinguishing tumors from surrounding tissue.

Using ICG may improve surgical outcomes by helping surgeons achieve clearer tumor margins, potentially leading to better progression-free survival rates, although further studies are needed to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indocyanine green fluorescence-guided surgery in head and neck cancer: A systematic review. De Ravin, E., Venkatesh, S., Harmsen, S., et al.[2022]

Indocyanine green (ICG) is increasingly used in colorectal surgery for its ability to enhance intraoperative visualization, including fluorescence angiography and detection of lymph node involvement, which improves surgical outcomes.

The use of ICG with near-infrared light provides detailed anatomical and functional information, leading to safer tumor removal and better preservation of surrounding structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indocyanine Green (ICG) and Colorectal Surgery: A Literature Review on Qualitative and Quantitative Methods of Usage. Simion, L., Ionescu, S., Chitoran, E., et al.[2023]

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]

Indocyanine green (ICG) is a fluorescent dye used in various surgical applications, including identifying sentinel lymph nodes and assessing skin perfusion during breast surgeries, highlighting its role in improving surgical outcomes.

ICG's ability to emit fluorescence when illuminated by near-infrared light allows for precise mapping of lymphatic networks and guidance in excising nonpalpable breast cancer, demonstrating its efficacy in oncological and reconstructive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of indocyanine green angiography in oncological and reconstructive breast surgery]. Struk, S., Honart, JF., Qassemyar, Q., et al.[2018]

Intraoperative use of indocyanine green (ICG) fluorescence imaging significantly reduced the anastomotic leak (AL) rate in rectal cancer surgery, with a lower rate observed in 926 patients using ICG compared to 1162 in the control group (OR 0.34).

The use of ICG also led to a decrease in overall complication rates and reoperation rates, indicating its potential to improve surgical outcomes in rectal cancer procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of intraoperative use of indocyanine green fluorescence imaging on the incidence of anastomotic leakage after rectal cancer surgery: a PRISMA-compliant systematic review and meta-analysis. Song, M., Liu, J., Xia, D., et al.[2021]

Indocyanine green (ICG) is a vital dye used in vitreoretinal surgery to improve visualization of delicate tissues, but its safety profile is limited, with reports of patients developing permanent central scotomas after surgery.

The use of ICG can enhance surgical techniques, but it does not guarantee improved visual outcomes, highlighting the need for careful application and consideration of safety issues during its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should Indocyanine green should be used to facilitate removal of the internal limiting membrane in macular hole surgery. Thompson, JT., Haritoglu, C., Kampik, A., et al.[2015]

Indocyanine green (ICG) is a low-toxicity dye that has been used in medicine since the 1950s, and it is now gaining traction for its ability to evaluate tissue perfusion and identify sentinel lymph nodes during surgeries.

ICG's applications are expanding, with potential benefits including reduced postoperative complications and improved outcomes in cancer detection and ophthalmologic procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indocyanine Green: Historical Context, Current Applications, and Future Considerations. Reinhart, MB., Huntington, CR., Blair, LJ., et al.[2022]

In a meta-analysis of 13 studies involving 4037 colorectal cancer patients, the use of indocyanine green fluorescence angiography (ICG-FA) significantly reduced the incidence of anastomotic leakage (AL) from 7.8% in the control group to 3.8% in the ICG group, indicating its efficacy in improving surgical outcomes.

ICG-FA also lowered the reoperation rates (2.6% in the ICG group vs. 6.9% in the control group) and overall complication rates (15.6% in the ICG group vs. 21.2% in the control group), suggesting that this technique enhances patient safety during colorectal surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does intraoperative indocyanine green fluorescence angiography decrease the incidence of anastomotic leakage in colorectal surgery? A systematic review and meta-analysis. Liu, D., Liang, L., Liu, L., et al.[2021]

Indocyanine green (ICG) fluorescence imaging has been successfully used to diagnose postoperative gastrointestinal fistulas, showing its potential as a safe and effective diagnostic tool.

In cases of large fistulas, both ICG and methylene blue were detected in drainage, but as the fistula size decreased, only ICG fluorescence remained visible, highlighting its utility in monitoring treatment progress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary application of indocyanine green fluorescence imaging in postoperative gastrointestinal fistula. Peng, Y., Fang, C., Zhu, G., et al.[2021]

Indocyanine green (ICG) fluorescence was successfully used in a laparoscopic lymph node biopsy to visualize and detect pathologic lymph nodes in a patient with suspected lymphoma, demonstrating its potential as a safe and effective method for this purpose.

The case highlights that ICG fluorescence can enhance the identification of lymphomatous tissue during surgery, suggesting a novel application that warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laparoscopic lymph node biopsy for lymphoma with a novel use of indocyanine green fluorescence in a 66-year-old male patient. Casaccia, M., Mora, M., Santori, G., et al.[2022]

Laser-assisted indocyanine green (ICG) fluorescent dye angiography significantly reduces the risk of anastomotic leaks in esophageal reconstructive surgery, enhancing patient safety.

In a case study of a 69-year-old male undergoing minimally invasive Ivor Lewis esophagectomy, the use of ICG imaging allowed for optimal site selection for anastomosis, leading to a smooth recovery and discharge within 6 days post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic evaluation of gastric conduit perfusion in minimally invasive Ivor Lewis esophagectomy. Fikfak, V., Gaur, P., Kim, MP.[2020]

References

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

Indocyanine green fluorescence-guided surgery in head and neck cancer: A systematic review. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Indocyanine Green (ICG) and Colorectal Surgery: A Literature Review on Qualitative and Quantitative Methods of Usage. [2023]

3. 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]

4. France pubmed.ncbi.nlm.nih.gov

[Use of indocyanine green angiography in oncological and reconstructive breast surgery]. [2018]

5. Italy pubmed.ncbi.nlm.nih.gov

Assessment of intraoperative use of indocyanine green fluorescence imaging on the incidence of anastomotic leakage after rectal cancer surgery: a PRISMA-compliant systematic review and meta-analysis. [2021]

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

Should Indocyanine green should be used to facilitate removal of the internal limiting membrane in macular hole surgery. [2015]

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

Indocyanine Green: Historical Context, Current Applications, and Future Considerations. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Does intraoperative indocyanine green fluorescence angiography decrease the incidence of anastomotic leakage in colorectal surgery? A systematic review and meta-analysis. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Preliminary application of indocyanine green fluorescence imaging in postoperative gastrointestinal fistula. [2021]

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

Laparoscopic lymph node biopsy for lymphoma with a novel use of indocyanine green fluorescence in a 66-year-old male patient. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Endoscopic evaluation of gastric conduit perfusion in minimally invasive Ivor Lewis esophagectomy. [2020]