Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study

J Vonk; F J Voskuil; J G de Wit; W T Heeman; W B Nagengast; G M van Dam; R A Feijen; Agw Korsten-Meijer; B van der Vegt; Mjh Witjes

doi:10.1007/s00259-021-05567-x

Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study

Eur J Nucl Med Mol Imaging. 2022 Apr;49(5):1640-1649. doi: 10.1007/s00259-021-05567-x. Epub 2021 Nov 5.

Authors

J Vonk¹, F J Voskuil^{1

2}, J G de Wit¹, W T Heeman^{3

4

5}, W B Nagengast⁶, G M van Dam^{3

7}, R A Feijen⁸, Agw Korsten-Meijer⁸, B van der Vegt^#², Mjh Witjes^#⁹

Affiliations

¹ Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands.
² Department of Pathology & Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Faculty Campus Fryslân, University of Groningen, Leeuwarden, the Netherlands.
⁵ LIMIS Development B.V, Leeuwarden, the Netherlands.
⁶ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁷ AxelaRx/TRACER B.V, Groningen, the Netherlands.
⁸ Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁹ Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands. m.j.h.witjes@umcg.nl.

^# Contributed equally.

Abstract

Purpose: Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery.

Methods: In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo.

Results: In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FI_mean), with SNIP tissue showing a median FI_mean of 77.54 (IQR 50.47-112.30) compared to 35.99 (IQR 21.48-57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78.

Conclusions: A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery.

Trial registration: NCT03925285.

Keywords: Inverted; Molecular imaging; Optical imaging; Papilloma; Paranasal sinus neoplasms; Vascular endothelial growth factor A.

Publication types

Clinical Study

MeSH terms

Bevacizumab / therapeutic use
Head and Neck Neoplasms*
Humans
Immunohistochemistry
Optical Imaging
Papilloma, Inverted* / diagnostic imaging
Papilloma, Inverted* / metabolism
Papilloma, Inverted* / surgery
Vascular Endothelial Growth Factor A / metabolism

Substances

Vascular Endothelial Growth Factor A
Bevacizumab

Associated data

ClinicalTrials.gov/NCT03925285