Theranostics 2020; 10(9):3994-4005. doi:10.7150/thno.43227 This issue Cite

Research Paper

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

Floris Jan Voskuil1*, Steven Jakob de Jongh2*, Wouter Tjerk Rudolph Hooghiemstra2,3, Matthijs David Linssen2,3, Pieter Jan Steinkamp4, Sebastiaan Antonius Hendrik Johannes de Visscher1, Kees-Pieter Schepman1, Sjoerd Geert Elias5, Gert-Jan Meersma2, Pascal Klaas Christiaan Jonker4, Jan Johannes Doff6, Annelies Jorritsma-Smit3, Wouter Bastiaan Nagengast2, Bert van der Vegt6, Dominic James Robinson7, Gooitzen Michell van Dam4,8, Max Johannes Hendrikus Witjes1✉

1. Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, the Netherlands
2. Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, the Netherlands
3. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, The Netherlands
4. Department of Surgery and Medical Imaging Center, University of Groningen, University Medical Center Groningen, the Netherlands
5. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, The Netherlands.
6. Department of Pathology & Medical Biology, University of Groningen, University Medical Center Groningen, the Netherlands
7. Center for Optical Diagnostics and Therapy, Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
8. TRACER Europe B.V. / AxerlaRx, Groningen, The Netherlands
*Both authors contributed equally to this work.

Citation:
Voskuil FJ, de Jongh SJ, Hooghiemstra WTR, Linssen MD, Steinkamp PJ, de Visscher SAHJ, Schepman KP, Elias SG, Meersma GJ, Jonker PKC, Doff JJ, Jorritsma-Smit A, Nagengast WB, van der Vegt B, Robinson DJ, van Dam GM, Witjes MJH. Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: A quantitative dose-escalation study. Theranostics 2020; 10(9):3994-4005. doi:10.7150/thno.43227. https://www.thno.org/v10p3994.htm
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Abstract

Graphic 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.

Keywords: fluorescence-guided imaging, intrinsic fluorescence, MDSFR/SFF spectroscopy, cetuximab-800CW, head and neck cancer


Citation styles

APA
Voskuil, F.J., de Jongh, S.J., Hooghiemstra, W.T.R., Linssen, M.D., Steinkamp, P.J., de Visscher, S.A.H.J., Schepman, K.P., Elias, S.G., Meersma, G.J., Jonker, P.K.C., Doff, J.J., Jorritsma-Smit, A., Nagengast, W.B., van der Vegt, B., Robinson, D.J., van Dam, G.M., Witjes, M.J.H. (2020). Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: A quantitative dose-escalation study. Theranostics, 10(9), 3994-4005. https://doi.org/10.7150/thno.43227.

ACS
Voskuil, F.J.; de Jongh, S.J.; Hooghiemstra, W.T.R.; Linssen, M.D.; Steinkamp, P.J.; de Visscher, S.A.H.J.; Schepman, K.P.; Elias, S.G.; Meersma, G.J.; Jonker, P.K.C.; Doff, J.J.; Jorritsma-Smit, A.; Nagengast, W.B.; van der Vegt, B.; Robinson, D.J.; van Dam, G.M.; Witjes, M.J.H. Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: A quantitative dose-escalation study. Theranostics 2020, 10 (9), 3994-4005. DOI: 10.7150/thno.43227.

NLM
Voskuil FJ, de Jongh SJ, Hooghiemstra WTR, Linssen MD, Steinkamp PJ, de Visscher SAHJ, Schepman KP, Elias SG, Meersma GJ, Jonker PKC, Doff JJ, Jorritsma-Smit A, Nagengast WB, van der Vegt B, Robinson DJ, van Dam GM, Witjes MJH. Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: A quantitative dose-escalation study. Theranostics 2020; 10(9):3994-4005. doi:10.7150/thno.43227. https://www.thno.org/v10p3994.htm

CSE
Voskuil FJ, de Jongh SJ, Hooghiemstra WTR, Linssen MD, Steinkamp PJ, de Visscher SAHJ, Schepman KP, Elias SG, Meersma GJ, Jonker PKC, Doff JJ, Jorritsma-Smit A, Nagengast WB, van der Vegt B, Robinson DJ, van Dam GM, Witjes MJH. 2020. Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: A quantitative dose-escalation study. Theranostics. 10(9):3994-4005.

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