A Ratiometric Threshold for Determining Presence of Cancer During Fluorescence-Guided Surgery

J Surg Oncol. 2015 Jul;112(1):2-8. doi: 10.1002/jso.23946. Epub 2015 Jun 12.


Background and objective: Fluorescence-guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However, a standardized method for quantitative assessment of disease-specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi-quantitatively delineate tumor from normal tissue.

Methods: Open-field and a closed-field imaging devices were used to quantify fluorescence in punch biopsy tissues sampled from primary tumors collected during a phase 1 trial evaluating the safety of cetuximab-IRDye800 in patients (n = 11) undergoing surgical intervention for head and neck cancer. Fluorescence ratios were calculated using mean fluorescence intensity (MFI) from punch biopsy normalized by MFI of patient-matched tissues. Ratios were compared to pathological assessment and a ratiometric threshold was established to predict presence of cancer.

Results: During open-field imaging using an intraoperative device, the threshold for muscle normalized tumor fluorescence was found to be 2.7, which produced a sensitivity of 90.5% and specificity of 78.6% for delineating disease tissue. The skin-normalized threshold generated greater sensitivity (92.9%) and specificity (81.0%).

Conclusion: Successful implementation of a semi-quantitative threshold can provide a scientific methodology for delineating disease from normal tissue during fluorescence-guided resection of cancer.

Keywords: fluorescence-guided surgery; head & neck cancer; standardized imaging; surgical oncology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / surgery*
  • Fluorescence
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / surgery*
  • Humans
  • Neoplasm Staging
  • Prognosis
  • ROC Curve
  • Surgery, Computer-Assisted*