Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Indocyanine green, ICG, First-window imaging, Near-infrared fluorescence imaging, Tumor-to-background ratio, Intraoperative imaging
Brief summary
This observational study will examine how closely first-window indocyanine green (ICG) fluorescence corresponds to the extent of head and neck squamous cell carcinoma identified by tissue biopsy. ICG is a fluorescent dye given into a vein during surgery. Patients receive ICG as part of their clinical care, independently of whether they participate in this study. The study plans to enroll 25 adults undergoing surgery for confirmed or strongly suspected cancer. Researchers will record near-infrared images obtained during clinical ICG use, compare them with tissue pathology, and measure the strength, timing, and duration of fluorescence. The research analysis will not guide clinical or surgical decisions. Participants will be followed through 24 hours after surgery.
Detailed description
This single-center, prospective observational cohort study evaluates the relationship between first-window ICG fluorescence and the biopsy-defined extent of head and neck squamous cell carcinoma during surgical resection. The decision to use intraoperative ICG is made as part of clinical care independently of study enrollment. Research activities consist of recording fluorescence imaging data and correlating those data with standard-of-care histopathology. First-window imaging captures fluorescence during initial dye perfusion after intraoperative administration. After tumor exposure and standard white-light inspection, the ICG regimen described for observation consists of a 2 mg intravenous bolus followed by a saline flush. Completion of the flush defines T0. Continuous near-infrared video is recorded from T0 through 3 minutes after T0 using an ICG-compatible imaging system. The described regimen includes three boluses totaling 6 mg ICG; actual doses and administration times are documented. Clinical dosing decisions remain with the treating team independently of study participation. Further dosing may be held for hypersensitivity or hemodynamic instability, and imaging may be stopped if it interferes with surgical workflow. Biopsies are obtained according to standard clinical practice, and their locations relative to fluorescence are documented. The research correlation of fluorescence with histopathology does not direct clinical or surgical decisions. Fluorescence measurements are compared with histopathology to estimate tumor-to-background ratio, sensitivity, specificity, time to fluorescence onset, time to peak contrast, and dose-dependent fluorescence dynamics. De-identified imaging data will be analyzed by the University of Alabama at Birmingham Department of Otolaryngology. Participants are followed through 24 hours after surgery. Adverse events considered at least possibly related to ICG are collected from the first dose through 24 hours after surgery.
Interventions
DRUGIndocyanine green
Clinical exposure of interest: intraoperative ICG. The regimen described for observation is three 2 mg IV boluses, each followed by a saline flush, totaling 6 mg. Actual doses and times are recorded; clinical dosing is determined independently of study participation.
PROCEDURENear-infrared fluorescence imaging
Continuous video from completion of the saline flush (T0) through 3 minutes after each bolus, using an FDA-cleared ICG-compatible NIR imaging system.
Sponsors
Washington University School of Medicine
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed, or strong clinical suspicion contingent on standard of care pre-operative assessment, of head and neck squamous cell carcinoma (HNSCC), preparing to undergo surgical resection. * At least 18 years of age. * The effects of ICG on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to surgery and for 1 week after surgery. Should a woman become pregnant or suspect she is pregnant during this time or should a man suspect he has fathered a child, s/he must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document.
Exclusion criteria
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ICG, sodium iodide, or other agents used in the study. * Thyroid radioactive uptake study within 1 week of ICG administration. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 1 day of surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor-to-background ratio (TBR) | During surgery, from completion of each post-ICG saline flush through 3 minutes after the flush, for three planned boluses (1 day) | TBR is calculated as the mean fluorescence intensity (MFI) within a region of interest (ROI) drawn over pathology-confirmed tumor tissue divided by the MFI within an ROI drawn over adjacent clinically normal tissue, as measured on intraoperative near-infrared fluorescence imaging. The mean TBR with 95% confidence intervals will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of Indocyanine Green (ICG) fluorescence for tumor detection | During surgery, from completion of each post-ICG saline flush through 3 minutes after the flush, for three planned boluses (1 day) | Defined as the proportion of histopathologically confirmed tumor regions correctly identified as fluorescent. A standardized fluorescence ratio (SFR) threshold, determined by receiver operating characteristic (ROC) analysis using the maximum Youden's J index, will be used to classify tissue as fluorescent-positive or fluorescent-negative. |
| Specificity of Indocyanine Green (ICG) fluorescence for tumor detection | During surgery, from completion of each post-ICG saline flush through 3 minutes after the flush, for three planned boluses (1 day) | Defined as the proportion of histopathologically confirmed normal tissue regions correctly identified as non-fluorescent. A standardized fluorescence ratio (SFR) threshold, determined by receiver operating characteristic (ROC) analysis using the maximum Youden's J index, will be used to classify tissue as fluorescent-positive or fluorescent-negative. |
| Time to first detectable tumor fluorescence | During surgery, from completion of each post-ICG saline flush through 3 minutes after the flush, for three planned boluses (1 day) | Time in seconds from completion of the saline flush after intravenous ICG administration (T0) to the first visible tumor fluorescence above background on serial intraoperative NIR imaging. |
| Time to peak tumor-to-background ratio | During surgery, from completion of each post-ICG saline flush through 3 minutes after the flush, for three planned boluses (1 day | Time in seconds from completion of the saline flush after intravenous ICG administration (T0) to the first visible tumor fluorescence above background on serial intraoperative NIR imaging. |
| Association between ICG dose and tumor-to-background ratio | During surgery, from completion of each post-ICG saline flush through 3 minutes after the flush, for three planned boluses (1 day) | Association between administered ICG dose, expressed in mg/kg after adjustment for body weight, and tumor-to-background ratio (TBR), evaluated using Pearson or Spearman correlation. TBR is the mean fluorescence intensity in pathology-confirmed tumor divided by that in adjacent clinically normal tissue. |
| Association between ICG dose and fluorescence washout kinetics | During surgery, from completion of each post-ICG saline flush through 3 minutes after the flush, for three planned boluses (1 day) | Relationship between administered ICG dose and the decline in tumor-to-background ratio over time, characterized by fitting exponential decay models to serial TBR measurements. |
Countries
United States
Contacts
CONTACTBharat Panuganti, MD, FACS
PRINCIPAL_INVESTIGATORBharat Panuganti, MD, FACS
Washington University School of Medicine
Outcome results
None listed