Canadian Optically-Guided Approach for Oral Lesions Surgical (COOLS) Trial: Study Protocol for a Randomized Controlled Trial

Background: Oral cancer is a major health problem worldwide. The 5-year survival rate ranges from 30-60%, andhas remained unchanged in the past few decades. This is mainly due to late diagnosis and high recurrence of thedisease. Of the patients who receive treatment, up to one third suffer from a recurrence or a second primarytumor. It is apparent that one major cause of disease recurrence is clinically unrecognized field changes whichextend beyond the visible tumor boundary. We have previously developed an approach using fluorescencevisualization (FV) technology to improve the recognition of the field at risk surrounding a visible oral cancer thatneeds to be removed and preliminary results have shown a significant reduction in recurrence rates.Method/Design: This paper describes the study design of a randomized, multi-centre, double blind, controlledsurgical trial, the COOLS trial. Nine institutions across Canada will recruit a total of 400 patients with oral severedysplasia or carcinoma in situ (N = 160) and invasive squamous cell carcinoma (N = 240). Patients will be stratifiedby participating institution and histology grade and randomized equally into FV-guided surgery (experimental arm)or white light-guided surgery (control arm). The primary endpoint is a composite of recurrence at or 1 cm withinthe previous surgery site with 1) the same or higher grade histology compared to the initial diagnosis (i.e., thediagnosis used for randomization); or 2) further treatment due to the presence of severe dysplasia or higherdegree of change at follow-up. This is the first randomized, multi-centre trial to validate the effectiveness of the FVguidedsurgery.Discussion: In this paper we described the strategies, novelty, and challenges of this unique trial involving asurgical approach guided by the FV technology. The success of the trial requires training, coordination, and qualityassurance across multiple sites within Canada. The COOLS trial, an example of translational research, may result inreduced recurrence rates following surgical treatment of early-stage oral cancer with significant impacts on survival,morbidity, patients’ quality of life and the cost to the health care system.Trial Registration: Clinicaltrials.gov NCT01039298