Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer - COOLS TRIAL

Oral squamous cell carcinoma (SCC) is a global disease responsible for \~300,000 new cancer cases each year. Local recurrence (\~30% of cases) and formation of second primary malignancy are common.2, 3 Cosmetic and/or functional compromise associated with treatment of disease stage is often significant. These statistics underscore the urgent need to develop a better approach in order to control this deadly disease. It is becoming increasingly apparent that oral cancers develop within wide fields of diseased tissue characterized by genetically altered cells that are widespread across the oral cavity and present in clinically and histologically normal oral mucosa. Complete removal of these lesions is difficult because high-risk changes frequently go beyond clinically visible tumor. In recognition of this, current 'best practice' is to remove SCC with a significant width (usually 10 mm) of surrounding normal-looking oral mucosa. However, since occult disease varies in size such approach often results in over-cutting (causing severe cosmetic and functional morbidity) or under removal of disease tissue, as evidenced by frequent positive surgical margins and high local and regional recurrence - a failure of the 'best practice. There is a wealth of literature that supports the use of tissue autofluorescence in the screening and diagnosis of precancers in the lung, uterine cervix, skin and oral cavity. This approach is already in clinical use in the lung and the mechanism of action of tissue autofluorescence has been well described in the cervix. Changes in fluorescence reflect a complex interplay of alterations to fluorophores in the tissue and structural changes in tissue morphology, each associated with progression of the disease. As one of the internationally leading teams in applying tissue fluorescence technology, we have shown that direct fluorescence visualization (FV) tools can identify clinically visible or occult premalignant and malignant lesions that are ass