Ameloblastoma is a
neoplasm arising in the craniofacial skeleton. Proliferating odontogenic epithelial cells comprise this benign, yet locally invasive
tumor, often causing severe disfiguration. High recurrence rate entails ablative surgical resection, which is the current standard of care, resulting in subsequent critical size osteocutaneous defects. The high incidence of BRAF mutations in
ameloblastoma, most notably the BRAF V600E mutation, enabled the use of BRAF inhibiting agent in a neoadjuvant setting. In this investigator-initiated, open-label study, three consecutive pediatric patients, with confirmed BRAF V600E
ameloblastoma deemed marginally resectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The use of upfront BRAF inhibitor treatment resulted in substantial
tumor regression, allowing for non-mutilating complete surgical removal, ad integrum bone regeneration and organ preservation. All patients showed a marked radiologic and clinical response to medical treatment, enabling successful conservative surgery. Microscopically, all patients showed evidence of minimal
residual tumor with extensive
tumor necrosis,
fibrosis and generation of new bone. At a median follow-up of 31 months, all patients remained free of disease. Face preservation
therapy was achieved in pediatric patients presenting with BRAF V600E mutated
ameloblastoma. Our study demonstrates the translational potential of targeted
therapy as a neoadjuvant agent. Patient-specific organ preservation
therapy should be considered as the new standard of care in
ameloblastoma, mainly for children and adolescents.