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

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 = 6) or dabrafenib with trametinib (n = 5). The median age was 19 (range = 10-83) years. Median treatment duration was 10 (range = 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 = 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.

BladeShield 101: A Novel Prehospital Digital Wearable Combat Casualty Card.

BACKGROUND: The Israeli Defense Forces-Medical Corps (IDF-MC) focuses on reducing preventable death by improving prehospital trauma care. High quality documentation of care can serve casualty care and to improve future care. Currently, paper casualty cards are used for documentation. Incomplete data acquisition and inadequate data handover are common. To resolve these deficits, the IDF-MC launched the BladeShield 101 project. OBJECTIVES: To assess the quality of casualty care data acquired by comparing standard paper casualty cards with the BladeShield 101. METHODS: The BladeShield 101 system consists of three components: a patient unit that records vital signs and medical care provided, a medical sensor that transmits to the patient unit, and a ruggedized mobile device that allows providers to access and document information. We compared all trauma registries of casualties treated between September 2019 and June 2020. RESULTS: The system was applied during the study period on 24 patients. All data were transferred to the military trauma registry within one day, compared to 72% (141/194) with a paper casualty card (P < 0.01). Information regarding treatment time was available in 100% vs. 43% (P < 0.01) of cases and 98% vs. 67% (P < 0.01) of treatments provided were documented comparing BladeShield 101 with paper cards, respectively. CONCLUSIONS: Using an autonomous system to record, view, deliver, and store casualty information may resolve most current information flow deficits. This solution will ultimately significantly improve individual patient care and systematic learning and development processes.

Upfront rational therapy in BRAF V600E mutated pediatric ameloblastoma promotes ad integrum mandibular regeneration.

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.

Predictability of Mandibular Autorotation After Le Fort I Maxillary Impaction in Case of Vertical Maxillary Excess.

A retrospective study of 20 patients treated for vertical maxillary excess between 2009 and 2010, solely by superior surgical repositioning of the maxilla. Clinical and radiological cephalometric parameters were analyzed statistically and their impact on achieving the predicted postoperative mandibular autorotation and on relapse. According to our study, patients presenting with an anterior open bite and a low occlusal plane angle might fail to achieve the predicted mandibular autorotation and are prone to postoperative relapse. No correlation was found between the extent of maxillary impaction and the presence of autorotation.

Unicystic ameloblastoma in an infant: a management dilemma.

The authors describe the conservative management of a rare case of unicystic ameloblastoma (mural subtype) in a 10-month-old girl, the youngest patient reported thus far in the literature. Rather than subject the infant to further surgery, it was decided to monitor her closely and perform an additional operation in the event of recurrence, thus enabling uninterrupted mandibular growth and tooth development. The patient is now 3.5 years old and periodic follow-up is ongoing, with no evidence of recurrence.

Oral effects of nonmyeloablative stem cell transplantation: a prospective observational study.

OBJECTIVE: Nonmyeloablative stem cell transplantation (NST) is a relatively new type of hematopoietic stem cell transplantation (HSCT) that has gained wider use in the last decade. Oral effects of NST have not been described. The goal of the study was to evaluate the oral mucosal effects, including oral acute graft versus host disease (aGVHD), in patients undergoing NST in comparison to patients undergoing myeloablative HSCT. METHOD AND MATERIALS: This prospective, longitudinal pilot study included 34 consecutive patients undergoing HSCT. Demographic data were collected. Patients were evaluated every 2 weeks between baseline and day 100 posttransplantation. Statistical methods included univariate and multivariable regression analyses (level of significance, P < .05) . RESULTS: Patients undergoing NST had significantly less oral aGVHD (P = .032, OR = 0.11, CI: 0.02-0.83). Systemic aGVHD-related lesions were common in all patients. The prevalence of opportunistic oral infections was not statistically different between the NST and ablative groups (P = .94). CONCLUSIONS: In this pilot study, cancer patients treated with NST had a lower incidence of oral aGVHD than those receiving myeloablative HSCT. The incidence of other oral soft tissue lesions, including opportunistic infections, was not affected by the type of HSCT.