EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial

Jaron G de Wit; Jasper Vonk; Floris J Voskuil; Sebastiaan A H J de Visscher; Kees-Pieter Schepman; Wouter T R Hooghiemstra; Matthijs D Linssen; Sjoerd G Elias; Gyorgy B Halmos; Boudewijn E C Plaat; Jan J Doff; Eben L Rosenthal; Dominic Robinson; Bert van der Vegt; Wouter B Nagengast; Gooitzen M van Dam; Max J H Witjes

doi:10.1038/s41467-023-40324-8

EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial

Jaron G de Wit, Jasper Vonk, Floris J Voskuil, Sebastiaan A H J de Visscher, Kees-Pieter Schepman, Wouter T R Hooghiemstra, Matthijs D Linssen, Sjoerd G Elias, Gyorgy B Halmos, Boudewijn E C Plaat, Jan J Doff, Eben L Rosenthal, Dominic Robinson, Bert van der Vegt, Wouter B Nagengast, Gooitzen M van Dam, Max J H Witjes^*

^*Corresponding author for this work

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Abstract

Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.

Original language	English
Article number	4952
Number of pages	10
Journal	Nature Communications
Volume	14
DOIs	https://doi.org/10.1038/s41467-023-40324-8
Publication status	Published - 16-Aug-2023

Keywords

Humans
Carcinoma, Squamous Cell/diagnostic imaging
Cetuximab
Coloring Agents
ErbB Receptors
Margins of Excision
Molecular Imaging
Mouth Neoplasms/diagnostic imaging
Radiopharmaceuticals

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de Wit, J. G., Vonk, J., Voskuil, F. J., de Visscher, S. A. H. J., Schepman, K.-P., Hooghiemstra, W. T. R., Linssen, M. D., Elias, S. G., Halmos, G. B., Plaat, B. E. C., Doff, J. J., Rosenthal, E. L., Robinson, D., van der Vegt, B., Nagengast, W. B., van Dam, G. M., & Witjes, M. J. H. (2023). EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial. Nature Communications, 14, Article 4952. https://doi.org/10.1038/s41467-023-40324-8

@article{a2193051c6bb42209b23d147ee9683af,

title = "EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial",

abstract = "Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.",

keywords = "Humans, Carcinoma, Squamous Cell/diagnostic imaging, Cetuximab, Coloring Agents, ErbB Receptors, Margins of Excision, Molecular Imaging, Mouth Neoplasms/diagnostic imaging, Radiopharmaceuticals",

author = "{de Wit}, {Jaron G} and Jasper Vonk and Voskuil, {Floris J} and {de Visscher}, {Sebastiaan A H J} and Kees-Pieter Schepman and Hooghiemstra, {Wouter T R} and Linssen, {Matthijs D} and Elias, {Sjoerd G} and Halmos, {Gyorgy B} and Plaat, {Boudewijn E C} and Doff, {Jan J} and Rosenthal, {Eben L} and Dominic Robinson and {van der Vegt}, Bert and Nagengast, {Wouter B} and {van Dam}, {Gooitzen M} and Witjes, {Max J H}",

note = "{\textcopyright} 2023. Springer Nature Limited.",

year = "2023",

month = aug,

day = "16",

doi = "10.1038/s41467-023-40324-8",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

de Wit, JG , Vonk, J , Voskuil, FJ , de Visscher, SAHJ , Schepman, K-P , Hooghiemstra, WTR, Linssen, MD, Elias, SG, Halmos, GB , Plaat, BEC , Doff, JJ, Rosenthal, EL, Robinson, D, van der Vegt, B , Nagengast, WB , van Dam, GM & Witjes, MJH 2023, 'EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial', Nature Communications, vol. 14, 4952. https://doi.org/10.1038/s41467-023-40324-8

TY - JOUR

T1 - EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients

T2 - a phase II trial

AU - de Wit, Jaron G

AU - Vonk, Jasper

AU - Voskuil, Floris J

AU - de Visscher, Sebastiaan A H J

AU - Schepman, Kees-Pieter

AU - Hooghiemstra, Wouter T R

AU - Linssen, Matthijs D

AU - Elias, Sjoerd G

AU - Halmos, Gyorgy B

AU - Plaat, Boudewijn E C

AU - Doff, Jan J

AU - Rosenthal, Eben L

AU - Robinson, Dominic

AU - van der Vegt, Bert

AU - Nagengast, Wouter B

AU - van Dam, Gooitzen M

AU - Witjes, Max J H

PY - 2023/8/16

Y1 - 2023/8/16

N2 - Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.

AB - Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.

KW - Humans

KW - Carcinoma, Squamous Cell/diagnostic imaging

KW - Cetuximab

KW - Coloring Agents

KW - ErbB Receptors

KW - Margins of Excision

KW - Molecular Imaging

KW - Mouth Neoplasms/diagnostic imaging

KW - Radiopharmaceuticals

U2 - 10.1038/s41467-023-40324-8

DO - 10.1038/s41467-023-40324-8

M3 - Article

C2 - 37587149

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

M1 - 4952

ER -

EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial

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Keywords

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