Neoadjuvant BRAF-targeted therapy for ameloblastoma of the mandible: an organ preservation approach

Shirly Grynberg, Marilena Vered, Ronnie Shapira-Frommer, Nethanel Asher, Guy Ben-Betzalel, Ronen Stoff, Yael Steinberg, Ninette Amariglio, Gahl Greenberg, Iris Barshack, Amos Toren, Ran Yahalom, Jacob Schachter, Gideon Rechavi, Ariel Hirschhorn*, Gadi Abebe Campino

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: 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 approximately 80% of mandible ameloblastomas, and BRAF inhibitors have demonstrated sustained responses in unresectable cases. Methods: 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. Results: Between 2017 and 2022, a total of 11 patients received dabrafenib (n ¼ 6) or dabrafenib with trametinib (n ¼ 5). The median age was 19 (range ¼ 10-83) years. Median treatment duration was 10 (range ¼ 3-20) months. All (100%) patients achieved a radiological response. Ten (91%) patients successfully converted to mandible preservation surgery with residual tumor enucleation. One patient attained complete radiological response, and surgery was not performed. Among the 10 surgically treated patients, all exhibited a pathological response, with 4 achieving near complete response and 6 partial response. At a median follow-up of 14 (range ¼ 7-37) months after surgery, 1 case of recurrence was observed. Grade 1-2 adverse effects were reported in 8 (73%) patients, with a single case of grade 3 (hepatitis). Dose modification was necessary for 3 patients, and 4 experienced treatment interruptions, while 1 patient permanently discontinued therapy. Conclusions: Neoadjuvant BRAF inhibition may offer a safe and effective strategy for organ preservation in mandible ameloblastoma treatment.

Original languageEnglish
Pages (from-to)539-546
Number of pages8
JournalJournal of the National Cancer Institute
Issue number4
StatePublished - 1 Apr 2024
Externally publishedYes


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