Abstract
Tumour-free margins ( >5 mm) in head and neck malignancies improve prognosis, possibly impacting the need for adjuvant treatment. In this phase II prospective, non-randomised trial (NCT05499065), we investigate the use of fluorescence imaging using the tumour targeting fluorescent tracer cetuximab-IRDye800CW combined with fresh frozen sectioning to identify inadequate margins intraoperatively in patients with oral squamous cell carcinoma. Primary objectives of our study are intraoperative detection of inadequate margins and additional resections, and feasibility of implementing fluorescence-guided fresh frozen sectioning (FG-FFS) into the clinical workflow. In this study, 10 out of 20 patients show inadequate margins after initial surgery; FG-FFS correctly classifies margin in 19 patients. Additional resections increase tumour-free margin rates from 50% to 85%, where anatomical boundaries limit further improvement in one patient. Intraoperative margin adjustment reduces the need for adjuvant treatment in seven patients. These findings demonstrate that FG-FFS is a reliable and feasible method for intraoperative margin assessment without delaying surgery.
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Due to patient privacy regulations, raw patient data are not available; only de-identified imaging data, safety data, clinical details, and laboratory data are available upon request. Proposals should be directed to the corresponding author (f.j.voskuil@umcg.nl); to gain access, data requestors will need to sign a data access agreement. Data will be saved for a minimum of 25 years, in accordance with Dutch legislation. Upon request, data can be made available to third parties within 6 weeks and can be accessed for 6 weeks thereafter. The source data underlying Figs. 2 and 3 and Tables 1 and 2 are provided as a Source data file; the remaining data are available in the Article. The study protocol is available as Supplementary Note in the Supplementary Information file. Source data are provided with this paper.
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Acknowledgements
We would like to thank Karien Kreeft-Polman and Ellen van den Ende-Schaap for their help in patient recruitment. Also, we would like to thank Maaike Barentsen, Tim Ramcharan, Lilo Janssens, Marco Abma and Erik Bleuel for their assistance in specimen processing. Finally, we would like to thank all patients who participated in this study.
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The study was conceptualised by T.S.N., B.K., B.v.d.V., M.J.H.W. and F.J.V. Fluorescent tracer was produced and made available by H.K.H. and H.H.B. Data acquisition was performed by T.S.N., B.K., D.R., M.J.H.W. and F.J.V. Intraoperative clinical decision-making was performed by T.S.N., B.K., J.B., S.A.H.J.d.V., G.B.H., B.E.C.P., J.J.D., K.P.S., B.v.d.V., M.J.H.W. and F.J.V. Data analysis was performed by T.S.N., B.K., D.R., M.J.H.W., F.J.V. T.S.N. and B.K. wrote and revised the manuscript with input, feedback, and acceptance from all authors. The study was supervised by M.J.H.W. and F.J.V.
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Nijboer, T.S., Keizers, B., Boeve, K. et al. Intraoperative fluorescence-guided fresh frozen sectioning for margin control in head and neck cancer: phase 2 clinical trial. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70264-y
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DOI: https://doi.org/10.1038/s41467-026-70264-y
