Neoadjuvant BRAF Targeted Therapy for Ameloblastoma of the Mandible: an Organ Preservation Approach.

Abstract

Ameloblastoma is a rare odontogenic neoplasm frequently located in the mandible. Standard treatment involves radical bone resection and immediate reconstruction, causing functional, aesthetic, and psychological impairments. The BRAF V600E mutation is present in about 80% of mandible ameloblastomas, and BRAF inhibitors have demonstrated sustained responses in unresectable cases. We identified ameloblastoma patients planned for ablative surgery and screened them for BRAF V600E mutation. Neoadjuvant BRAF inhibitors were offered to facilitate jaw preservation surgery. Retrospective data collection encompassed treatment regimens, tolerability, tumor response, and conversion to mandible preservation surgery. Between 2017 and 2022, eleven patients received Dabrafenib (n = 6)/Dabrafenib+Trametinib (n = 5). The median age was 19 years (10-83). Median treatment duration was 10 months (3-20). All patients achieved a radiological response (RR = 100%). Ten patients (91%) successfully converted to mandible preservation surgery with residual tumor enucleation. One patient attained complete radiological response, and surgery was not performed. Among the ten surgically treated patients, all exhibited a pathological response, with four achieving near complete response and six partial response. At a median follow-up of fourteen months (7-37) after surgery, one case of recurrence was observed. Grade 1-2 adverse events were reported in eight patients (73%), with a single case of grade 3 (hepatitis). Dose modification was necessary for three patients, and four experienced treatment interruptions, while one patient permanently discontinued therapy. Neoadjuvant BRAF inhibition may offer a safe and effective strategy for organ preservation in mandible ameloblastoma treatment.