Nicholas J Ledderhof1, Marco F Caminiti2, Grace Bradley3, David K Lam4. 1. Chief Resident, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada. 2. Assistant Professor, Department of Oral and Maxillofacial Surgery, University of Toronto, Toronto, ON, Canada. 3. Professor and Head, Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada. 4. Assistant Professor and Head, Department of Oral and Maxillofacial Surgery, University of Toronto, Toronto, ON, Canada. Electronic address: david.lam@utoronto.ca.
Abstract
PURPOSE: The antimetabolite drug, 5-fluorouracil (5-FU), is used in the treatment of various cancers, including basal cell carcinomas (BCCs). The authors hypothesized that keratocystic odontogenic tumors (KOTs) would respond to 5-FU treatment because of their similarities to BCCs in molecular etiopathogenesis. MATERIALS AND METHODS: An ambispective cohort study of the treatment efficacy of topical 5-FU on KOTs was conducted. Independent variables included the topical application of 5% 5-FU or modified Carnoy's solution (MC) after enucleation and peripheral ostectomy at the University of Toronto from 2006 through 2014. Outcome variables included time to recurrence and peripheral nerve injury. KOT specimens in these patients were immunostained with p53, Ki-67, thymidylate synthetase (TS), thymidylate phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) antibodies. Semiquantitative staining scores were calculated for all immunohistochemistry sections examined. Descriptive statistics were computed using Fisher exact test and Kaplan-Meier analysis as appropriate with the P value set at .05. RESULTS: Thirty-two patients with 32 KOTs were reviewed (41% in women and 59% in men). There were no KOT recurrences in the 5-FU group (n = 11), whereas there were 4 recurrences in the MC group (n = 21; P = .190). There was a significantly lower incidence of inferior alveolar nerve paresthesia with 5-FU treatment (P = .039). Immunohistochemical staining showed upregulation of TP (P < .0001) and DPD (P < .0001) and no change in TS (P > .05) in inflamed KOTs. CONCLUSIONS: 5-FU effectively treats KOTs with less postoperative morbidity than conventional treatment with MC. Low TS and upregulated TP expressions in inflamed KOTs suggest increased 5-FU efficacy in inflamed KOTs. Topical 5-FU is a novel therapy for KOTs and provides a targeted molecular approach to treatment.
PURPOSE: The antimetabolite drug, 5-fluorouracil (5-FU), is used in the treatment of various cancers, including basal cell carcinomas (BCCs). The authors hypothesized that keratocystic odontogenic tumors (KOTs) would respond to 5-FU treatment because of their similarities to BCCs in molecular etiopathogenesis. MATERIALS AND METHODS: An ambispective cohort study of the treatment efficacy of topical 5-FU on KOTs was conducted. Independent variables included the topical application of 5% 5-FU or modified Carnoy's solution (MC) after enucleation and peripheral ostectomy at the University of Toronto from 2006 through 2014. Outcome variables included time to recurrence and peripheral nerve injury. KOT specimens in these patients were immunostained with p53, Ki-67, thymidylate synthetase (TS), thymidylate phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) antibodies. Semiquantitative staining scores were calculated for all immunohistochemistry sections examined. Descriptive statistics were computed using Fisher exact test and Kaplan-Meier analysis as appropriate with the P value set at .05. RESULTS: Thirty-two patients with 32 KOTs were reviewed (41% in women and 59% in men). There were no KOT recurrences in the 5-FU group (n = 11), whereas there were 4 recurrences in the MC group (n = 21; P = .190). There was a significantly lower incidence of inferior alveolar nerve paresthesia with 5-FU treatment (P = .039). Immunohistochemical staining showed upregulation of TP (P < .0001) and DPD (P < .0001) and no change in TS (P > .05) in inflamed KOTs. CONCLUSIONS:5-FU effectively treats KOTs with less postoperative morbidity than conventional treatment with MC. Low TS and upregulated TP expressions in inflamed KOTs suggest increased 5-FU efficacy in inflamed KOTs. Topical 5-FU is a novel therapy for KOTs and provides a targeted molecular approach to treatment.