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Original Investigation |

Fluorescence Visualization–Guided Surgery for Early-Stage Oral Cancer

Catherine F. Poh, DDS, PhD1,2,3,4; Donald W. Anderson, MD1,2,3; J. Scott Durham, MD1,2,3; Jiahua Chen, PhD1,2,3; Kenneth W. Berean, MD1,2,3; Calum E. MacAulay, PhD4; Miriam P. Rosin, PhD4,5
[+] Author Affiliations
1Division of Otolaryngology–Head and Neck Surgery, Department of Oral Biological and Medical Science, University of British Columbia, Vancouver, Canada
2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
3Department of Statistics, University of British Columbia, Vancouver, Canada
4Integrative Oncology and Cancer Control Research Program, BC Cancer Research Centre, Vancouver, British Columbia, Canada
5Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
JAMA Otolaryngol Head Neck Surg. 2016;142(3):209-216. doi:10.1001/jamaoto.2015.3211.
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Importance  The prevalence of genetically altered cells in oral cancers has a negative influence on the locoregional recurrence rate and lowers survival. Fluorescence visualization (FV) can identify clinically occult, high-risk oral lesions by allowing health care professionals and surgeons to visualize and map occult disease. This process may improve overall survival by decreasing rates of locoregional recurrence.

Objective  To assess the efficacy of FV-guided surgery in reducing locoregional recurrence and improving overall survival.

Design, Setting, and Participants  A retrospective, case-control observational study was conducted on patients registered at a single oral oncology clinic from September 1, 2004, to August 31, 2009. The study included 246 patients 18 years or older with a diagnosis of a high-grade lesion (severe dysplasia or carcinoma in situ) or squamous cell carcinoma of less than 4 cm who underwent curative surgical treatment with at least 1 follow-up visit. Among these patients, 154 underwent surgery with FV guidance (FV group) and the other 92 underwent conventional surgery (control group). Demographic and lesional characteristics and outcomes were collected, and the key factors for the efficacy of FV-guided surgery were examined. Follow-up was completed on December 31, 2011, and data were analyzed from May 1 to November 30, 2013.

Main Outcomes and Measures  Local recurrence of oral lesions with a histologic grade of severe dysplasia or higher, the presence of regional failure (ie, a metastatic lesion in the cervical lymph nodes), or disease-free survival after surgery.

Results  Among the 246 patients included in the study (mean [SD] age, 60 [12] years; 108 women and 138 men), 156 had squamous cell carcinoma and 90 had high-grade lesions. There were no significant differences between the FV (n = 154) and control (n = 92) groups in age, smoking history, anatomical site of the lesion, tumor size, and previous oral cancer. Among the 156 patients with squamous cell carcinoma, the 92 patients in the FV group showed significant reduction in the 3-year local recurrence rate, from 40.6% (26 of 64 patients) to 6.5% (6 of 92 patients) (P < .001). Among the 90 patients with high-grade lesions, the 62 patients in the FV group showed a reduction in local recurrence rate from 11 of 28 patients (39.3%) to 5 of 62 patients (8.1%) (P < .001). The data also indicated that, compared with conventional surgery, the FV-guided approach for squamous cell carcinoma was associated with less regional failure (14 of 92 patients [15.2%] vs 16 of 64 [25.0%]; P = .08) and death (12 of 92 patients [13.0%] vs 13 of 64 [20.3%]; P = .22), although these differences were not statistically significant.

Conclusions and Relevance  In this study, the use of FV as part of the surgical margin decision process significantly reduced the rate of local recurrence in preinvasive high-grade and early-stage oral cancers. An ongoing multicenter, phase 3, randomized surgical trial has completed accrual, and the data will be used to validate the results of this study.

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Figure 1.
Study Schema

The numbers of patients, their diagnoses, and the types of treatment they received are shown. CIS indicates carcinoma in situ; D, dysplasia; D3, severe dysplasia; FV, fluorescence visualization; HGL, high-grade lesions; and SCC, squamous cell carcinoma.

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Figure 2.
Representative Clinical Lesion Assessment Using White Light (WL) and Fluorescence Visualization (FV)

A, A WL image of an ill-defined red lesion at the left lateral tongue. B, The clinical tumor boundary is outlined using a blue skin marker. C, FV image at the same area. D, The FV boundary is outlined using a green marker.

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Figure 3.
Kaplan-Meier Plot of Time to Outcomes

Kaplan-Meier plots represent probabilities of not developing the outcome of interest. FV indicates fluorescence visualization; HGL, high-grade lesion; and SCC, squamous cell carcinoma.

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