Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: A quantitative dose-escalation study

Floris Jan Voskuil, Steven Jakob de Jongh, Wouter Tjerk Rudolph Hooghiemstra, Matthijs David Linssen, Pieter Jan Steinkamp, Sebastiaan Antonius Hendrik Johannes de Visscher, Kees-Pieter Schepman, Sjoerd Geert Elias, Gert-Jan Meersma, Pascal Klaas Christiaan Jonker, Jan Johannes Doff, Annelies Jorritsma-Smit, Wouter Bastiaan Nagengast, Bert van der Vegt, Dominic James Robinson, Gooitzen Michell van Dam, Max Johannes Hendrikus Witjes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
62 Downloads (Pure)

Abstract

Tumor-positive resection margins are present in up to 23% of head and neck cancer (HNC) surgeries, as intraoperative techniques for real-time evaluation of the resection margins are lacking. In this study, we investigated the safety and potential clinical value of fluorescence-guided imaging (FGI) for resection margin evaluation in HNC patients. We determined the optimal cetuximab-800CW dose by quantification of intrinsic fluorescence values using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy. Methods: Five cohorts of three HNC patients received cetuximab-800CW systemically: three single dose cohorts (10, 25, 50 mg) and two cohorts pre-dosed with 75 mg unlabeled cetuximab (15 or 25 mg). Fluorescence visualization and MDSFR/SFF spectroscopy quantification was performed and were correlated to histopathology. Results: There were no study-related adverse events higher than Common Terminology Criteria for Adverse Events grade-II. Quantification of intrinsic fluorescence values showed a dose-dependent increase in background fluorescence in the single dose cohorts (p<0.001, p<0.001), which remained consistently low in the pre-dosed cohorts (p=0.6808). Resection margin status was evaluated with a sensitivity of 100% (4/4 tumor-positive margins) and specificity of 91% (10/11 tumor-negative margins). Conclusion: A pre-dose of 75 mg unlabeled cetuximab followed by 15 mg cetuximab-800CW was considered the optimal dose based on safety, fluorescence visualization and quantification of intrinsic fluorescence values. We were able to use a lower dose cetuximab-800CW than previously described, while remaining a high sensitivity for tumor detection due to application of equipment optimized for IRDye800CW detection, which was validated by quantification of intrinsic fluorescence values.

Original languageEnglish
Pages (from-to)3994-4005
Number of pages12
JournalTheranostics
Volume10
Issue number9
DOIs
Publication statusPublished - 2020

Keywords

  • fluorescence-guided imaging
  • intrinsic fluorescence
  • MDSFR/SFF spectroscopy
  • cetuximab-800CW
  • head and neck cancer
  • DISEASE-SPECIFIC SURVIVAL
  • SURGICAL NAVIGATION
  • LOCAL RECURRENCE
  • SAFETY
  • ALPHA

Cite this