Abstract
Complete removal and negative margins are the goal of any surgical resection of primary oral cavity carcinoma. Current approaches to determine tumor boundaries rely heavily on surgeons’ expertise, and final histopathological reports are usually only available days after surgery, precluding contemporaneous re-assessment of positive margins. Intraoperative optical imaging could address this unmet clinical need. Using mouse models of oral cavity carcinoma, we demonstrated that PARPi-FL, a fluorescent PARP inhibitor targeting the enzyme PARP1/2, can delineate oral cancer and accurately identify positive margins, both macroscopically and at cellular resolution. PARPi-FL also allowed identification of compromised margins based on fluorescence hotspots, which were not seen in margin-negative resections and control tongues. PARPi-FL was further able to differentiate tumor from low-grade dysplasia. Intravenous injection of PARPi-FL has significant potential for clinical translation and could aid surgeons in assessing oral cancer margins in vivo.
Highlights
Complete removal and negative margins are the goal of any surgical resection of primary oral cavity carcinoma
PARP1 is overexpressed in mouse models of tongue cancer
With an orthotopic mouse model, we observed the presence of microscopic tumor islands around the main tumor site, an archetypical feature of squamous cell carcinoma (Fig. 1a)
Summary
Complete removal and negative margins are the goal of any surgical resection of primary oral cavity carcinoma. The gold standard for negative-margin resection is the histological presence of normal tissue surrounding the tumor to a distance of at least 5 mm[6] This usually requires the arbitrary removal of large amounts of healthy tissue, often leads to large surgical defects requiring complex procedures for reconstruction and, depending on the location of the tumor, may cause irreversible impairment of phonation, mastication, gustation, and s wallowing[9]. This novel definition of close margins stratifies patients for local recurrence better than the arbitrary 5 mm cutoff that has been used for d ecades[6] Despite this new cutoff in OSCC, if histologic margins are smaller than 5 mm, administration of adjuvant treatment remains, in most cases, the standard of care[10,11]. With more specific methods being unavailable, surgeons rely heavily on imprecise visual inspection and p alpation[14]
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