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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a special dye, Indocyanine Green (ICG), can help surgeons reduce fistulas in patients undergoing throat cancer surgery. A fistula occurs when saliva leaks from the throat after surgery, slowing healing. Surgeons use the ICG dye to check blood flow in the throat during surgery to see if it helps prevent these leaks. Half of the participants will receive this ICG scan, while the other half will not, allowing for a comparison of results. This trial is for individuals who have had throat cancer, are undergoing throat surgery after radiation, and have a throat area suitable for scanning with the dye. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

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 prior data suggests that the ICG scan is safe for reducing fistulas after throat cancer surgery?

Research has shown that using ICG dye in surgeries is generally safe. ICG has been used in many medical procedures for a long time and rarely causes serious allergic reactions. However, people allergic to iodine might react to ICG, so doctors take extra care with these patients.

Other studies have demonstrated that ICG helps surgeons see blood flow in tissues. This visibility aids in deciding whether to remove parts with poor blood flow during surgery, which can improve healing and reduce complications like fistulas—unwanted openings that leak—after throat surgeries.

Overall, the safety of ICG dye is well-documented, and it is usually well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using ICG dye in throat cancer surgery because it offers a unique way to improve surgical outcomes. Unlike the standard reconstructive methods, which don't provide real-time information about tissue health, ICG dye acts as a vascular contrast agent that highlights blood flow in the tissue. By using the SPY Elite imaging device, surgeons can visualize how well blood is reaching the pharyngeal tissue during surgery. This enables them to identify and remove poorly perfused areas, potentially reducing the risk of fistulas, a common complication after surgery. The ability to assess tissue health in real-time could make surgeries safer and recovery smoother for patients.

What evidence suggests that the ICG scan is effective for reducing fistulas after throat cancer surgery?

Research has shown that a special dye called indocyanine green (ICG) can help predict and reduce the risk of fistulas, which are abnormal connections, after throat surgery. In this trial, participants in the experimental arm will receive ICG imaging to assess blood flow to throat tissue during surgery. If blood flow is poor, surgeons can take steps to improve healing. Studies have found that using ICG in less invasive esophagus surgery helped lower the risk of complications. This suggests that using ICG in throat cancer surgery might also reduce fistulas by identifying areas with poor blood flow. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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) 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]

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) 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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5710566/

Laser-Assisted Indocyanine Green Dye Angiography for ... Indocyanine green dye angiography can be used to evaluate pharyngeal mucosa after salvage laryngectomy and anticipate fistula formation.

2. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/2627923

Laser-Assisted Indocyanine Green Dye Angiography for ... Indocyanine green dye angiography can be used to evaluate pharyngeal mucosa after salvage laryngectomy and anticipate fistula formation.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28520896/

Laser-Assisted Indocyanine Green Dye Angiography for ... Ten patients (27%) developed a postoperative fistula. No significant difference was found in fistula rate between patients who underwent neck ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16115

Effect of fluorescent imaging using indocyanine green on ... The aim of this study was to determine the impact of ICG during minimally invasive esophagectomy (MIE) in reducing the rates of anastomotic failure.

5. link.springer.com link.springer.com/article/10.1245/s10434-019-07262-6

Intraoperative Fluorescent Angiography Predicts ... Intraoperative indocyanine green angiography can assess hypoperfusion in patients and predict risk of PCFs after salvage laryngectomy, and can ...

6. withpower.com withpower.com/trial/icg-dye-to-reduce-fistulas-after-throat-cancer-surgery-10a65

ICG Dye to Reduce Fistulas After Throat Cancer Surgery This Phase 2 medical study run by University Health Network, Toronto is evaluating whether ICG dye will have tolerable side effects & efficacy for patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10277941/

Application of indocyanine green in surgery: A review ... ICG is very safe, with rare cases of anaphylaxis and caution regarding potential cross-reactions in patients with iodine sensitivity[57]. It has a long history ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1010518213003314

Impact of indocyanine green fluorescent image-guided ... In parapharyngeal space dissection, significant complications such as dysphagia and carotid artery rupture have been reported. In order to resect tumours ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8899428/

Clinical application of indocyanine green fluorescence ... ICG-mediated NIF imaging technology provides a new method for observing and completely resecting tumors under direct vision during operation.

10. jprasurg.com jprasurg.com/article/S1748-6815(23)00442-4/abstract

Outcome analysis of free flap reconstruction for head and ... We found that free flap surgery with intraoperative ICG angiography significantly decreased total flap failure rate and significantly increased ...