Intraoperative fluorescence in solid head and neck cancer: A scoping review

doi:10.1007/s00405-025-09442-5

Review

. 2025 May 17.

doi: 10.1007/s00405-025-09442-5. Online ahead of print.

Intraoperative fluorescence in solid head and neck cancer: A scoping review

Brian A Keith^{1

2}, Alejandro R Marrero-Gonzalez^{1

3}, Isabelle J Chau^{1

4}, Shaun A Nguyen⁵, William G Albergotti¹, Alexandra E Kejner¹, Jason G Newman¹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, MSC 550, Charleston, SC, 29425, USA.
² School of Osteopathic Medicine, Campbell University, Lillington, NC, USA.
³ The University of Puerto Rico School of Medicine, San Juan, Puerto Rico, USA.
⁴ New York Medical College School of Medicine, Valhalla, NY, USA.
⁵ Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, MSC 550, Charleston, SC, 29425, USA. nguyensh@musc.edu.

PMID: 40380992
DOI: 10.1007/s00405-025-09442-5

Review

Intraoperative fluorescence in solid head and neck cancer: A scoping review

Brian A Keith et al. Eur Arch Otorhinolaryngol. 2025.

. 2025 May 17.

doi: 10.1007/s00405-025-09442-5. Online ahead of print.

Authors

Brian A Keith^{1

2}, Alejandro R Marrero-Gonzalez^{1

3}, Isabelle J Chau^{1

4}, Shaun A Nguyen⁵, William G Albergotti¹, Alexandra E Kejner¹, Jason G Newman¹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, MSC 550, Charleston, SC, 29425, USA.
² School of Osteopathic Medicine, Campbell University, Lillington, NC, USA.
³ The University of Puerto Rico School of Medicine, San Juan, Puerto Rico, USA.
⁴ New York Medical College School of Medicine, Valhalla, NY, USA.
⁵ Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, MSC 550, Charleston, SC, 29425, USA. nguyensh@musc.edu.

PMID: 40380992
DOI: 10.1007/s00405-025-09442-5

Abstract

Purpose: Obtaining negative margins in primary tumor resection is essential to decreasing recurrence and mortality. Fluorescence imaging may aid in complete tumor removal. As fluorescent agents are still under clinical trial investigation for use in head and neck cancer (HNC), their effectiveness in intraoperative margin assessment (IMA) remains unclear. This scoping review examines the use of fluorescent-guided surgery (FGS) in the treatment of HNC, highlighting significant opportunities in this nascent field.

Methods: PubMed, Scopus, CINAHL, and Cochrane Library were searched from inception through March 22, 2024. This study was conducted under PRISMA-ScR guidelines. Data on study characteristics, fluorescence and imaging techniques, imaging efficacy, and diagnostic accuracy were extracted.

Results: Twenty-seven prospective studies from 2013 to 2024 on intraoperative FGS in HNC, involving 455 patients from six countries, were included. Studies ranged from preclinical to phase II trials, applying various fluorescent techniques, predominantly indocyanine green and IRDye800CW, to enhance surgical precision. Imaging assessments were conducted in-vivo, ex-vivo, or both, using a wide range of devices and taking an additional 0 to 30 min intraoperatively. Quantitative measures like signal-to-background ratio and mean fluorescent intensity suggested variable diagnostic accuracy across studies. FGS shows great potential in improving IMA, although standardization in methodologies and reporting is needed.

Conclusion: This scoping review highlights the potential of intraoperative FGS to enhance treatment accuracy in solid HNC, though variability in diagnostic efficacy and a lack of standardized methodologies persist. Advancements in fluorophore technology and uniform procedural protocols are essential to optimize surgical outcomes and move towards personalized HNC interventions.

Keywords: Fluorescent-guided surgery; Head and neck cancer; Intraoperative imaging; Intraoperative margin assessment.

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Conflict of interest statement

Declarations. Institutional review board statement: Not applicable. Compliance with ethical standards: As this manuscript is a scoping review analyzing existing published literature, we adhered to ethical principles by ensuring transparency in our methodology, accurately representing the findings of included studies, and avoiding any potential for bias in our interpretation and reporting of results. No ethical approval was required as we are not collecting primary data from human participants. Conflicts of interest: AEK is a speaker for Vioptix Inc and Cooper Surgical; JGN is a consultant for Castle Biosciences, Hologic Inc., CelSci Inc., and Regeneron.

References

1. Kim KJ, Kim KJ, Choi J, Kim NH, Kim SG (2023) Linear association between radioactive iodine dose and second primary malignancy risk in thyroid cancer. J Natl Cancer Inst 115(6):695–702. https://doi.org/10.1093/jnci/djad040 - DOI - PubMed - PMC
1. Eldeeb H, Macmillan C, Elwell C, Hammod A (2012) The effect of the surgical margins on the outcome of patients with head and neck squamous cell carcinoma: single institution experience. Cancer Biol Med 9(1):29–33. https://doi.org/10.3969/j.issn.2095-3941.2012.01.005 - DOI - PubMed - PMC
1. Ravasz LA, Slootweg PJ, Hordijk GJ, Smit F, van der Tweel I (1991) The status of the resection margin as a prognostic factor in the treatment of head and neck carcinoma. J Craniomaxillofac Surg 19(7):314–318. https://doi.org/10.1016/s1010-5182(05)80339-7 - DOI - PubMed
1. Kurita H, Nakanishi Y, Nishizawa R, Xiao T, Kamata T, Koike T et al (2010) Impact of different surgical margin conditions on local recurrence of oral squamous cell carcinoma. Oral Oncol 46(11):814–817. https://doi.org/10.1016/j.oraloncology.2010.08.014 - DOI - PubMed
1. Nocon CC, Ajmani GS, Bhayani MK (2018) Association of facility volume with positive margin rate in the surgical treatment of head and neck cancer. JAMA Otolaryngol Head Neck Surg 144(12):1090–1097. https://doi.org/10.1001/jamaoto.2018.2421 - DOI - PubMed - PMC

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[1] Kim KJ, Kim KJ, Choi J, Kim NH, Kim SG (2023) Linear association between radioactive iodine dose and second primary malignancy risk in thyroid cancer. J Natl Cancer Inst 115(6):695–702. https://doi.org/10.1093/jnci/djad040 - DOI - PubMed - PMC

[2] Kim KJ, Kim KJ, Choi J, Kim NH, Kim SG (2023) Linear association between radioactive iodine dose and second primary malignancy risk in thyroid cancer. J Natl Cancer Inst 115(6):695–702. https://doi.org/10.1093/jnci/djad040 - DOI - PubMed - PMC

[3] Eldeeb H, Macmillan C, Elwell C, Hammod A (2012) The effect of the surgical margins on the outcome of patients with head and neck squamous cell carcinoma: single institution experience. Cancer Biol Med 9(1):29–33. https://doi.org/10.3969/j.issn.2095-3941.2012.01.005 - DOI - PubMed - PMC

[4] Eldeeb H, Macmillan C, Elwell C, Hammod A (2012) The effect of the surgical margins on the outcome of patients with head and neck squamous cell carcinoma: single institution experience. Cancer Biol Med 9(1):29–33. https://doi.org/10.3969/j.issn.2095-3941.2012.01.005 - DOI - PubMed - PMC

[5] Ravasz LA, Slootweg PJ, Hordijk GJ, Smit F, van der Tweel I (1991) The status of the resection margin as a prognostic factor in the treatment of head and neck carcinoma. J Craniomaxillofac Surg 19(7):314–318. https://doi.org/10.1016/s1010-5182(05)80339-7 - DOI - PubMed

[6] Ravasz LA, Slootweg PJ, Hordijk GJ, Smit F, van der Tweel I (1991) The status of the resection margin as a prognostic factor in the treatment of head and neck carcinoma. J Craniomaxillofac Surg 19(7):314–318. https://doi.org/10.1016/s1010-5182(05)80339-7 - DOI - PubMed

[7] Kurita H, Nakanishi Y, Nishizawa R, Xiao T, Kamata T, Koike T et al (2010) Impact of different surgical margin conditions on local recurrence of oral squamous cell carcinoma. Oral Oncol 46(11):814–817. https://doi.org/10.1016/j.oraloncology.2010.08.014 - DOI - PubMed

[8] Kurita H, Nakanishi Y, Nishizawa R, Xiao T, Kamata T, Koike T et al (2010) Impact of different surgical margin conditions on local recurrence of oral squamous cell carcinoma. Oral Oncol 46(11):814–817. https://doi.org/10.1016/j.oraloncology.2010.08.014 - DOI - PubMed

[9] Nocon CC, Ajmani GS, Bhayani MK (2018) Association of facility volume with positive margin rate in the surgical treatment of head and neck cancer. JAMA Otolaryngol Head Neck Surg 144(12):1090–1097. https://doi.org/10.1001/jamaoto.2018.2421 - DOI - PubMed - PMC

[10] Nocon CC, Ajmani GS, Bhayani MK (2018) Association of facility volume with positive margin rate in the surgical treatment of head and neck cancer. JAMA Otolaryngol Head Neck Surg 144(12):1090–1097. https://doi.org/10.1001/jamaoto.2018.2421 - DOI - PubMed - PMC

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Intraoperative fluorescence in solid head and neck cancer: A scoping review

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Intraoperative fluorescence in solid head and neck cancer: A scoping review

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