Correlation of BRAF mutational status with clinical characteristics and survival outcomes of patients with ameloblastoma: the experience of 11 Italian centres.

AIMS: Ameloblastoma is a rare odontogenic tumour with an aggressive local behaviour. Mutations in the mitogen-activated protein kinase pathway, namely BRAF V600E mutations, are a common finding. To date, there is no clear correlation between BRAF V600 mutation and clinical outcome. METHODS: We retrospectively reviewed the medical records of patients who underwent surgery for ameloblastoma between May 1998 and June 2018, at 11 participating Italian centres. BRAF mutational status was evaluated by quantitative PCR/pyrosequencing. The primary end points were to determine BRAF mutational status in primitive and recurrent ameloblastoma, and to assess the relapse-free interval (RFI); the secondary end point was to investigate the correlation of BRAF mutational status with the clinical features of the tumour and survival outcomes. RESULTS: Overall, 74 patients were included: 33 (44.5%) were BRAF wild type and 41 (55.4%) BRAF V600 mutated. BRAF V600 mutated ameloblastomas occurred more frequently in younger patients (p=0.0031), were located at the mandible (p=0.0009) and presented with unicystic variant. After a median follow-up of 60 months, 21 (28.3%) patients relapsed (30.3% and 26.8% in the BRAF wild type and BRAF mutated group, respectively). At univariable Cox models, none of the investigated variables, including microscopic margin involvement, was associated with RFI. CONCLUSIONS: Local recurrence occurs in 30% of patients with ameloblastoma. BRAFV600 mutation is associated with younger age, mandibular localisation and with unicystic ameloblastoma. Neither BRAF mutation nor microscopically positive surgical margins were associated with RFI. Further studies are needed to elucidate outcomes of this rare disease according to clinical, histopathological and comprehensive molecular features.

Osteonecrosis of the Jaw in Patients With Metastatic Renal Cell Cancer Treated With Bisphosphonates and Targeted Agents: Results of an Italian Multicenter Study and Review of the Literature.

Osteonecrosis of the jaw (ONJ) associated with the use of bisphosphonates has been rarely reported in metastatic renal cell cancer (RCC) patients. Since the introduction of combined therapies consisting of nitrogen-containing bisphosphonates (NBPs) and targeted agents, an increasing number of RCC patients were reported to develop ONJ, suggesting that therapeutic angiogenesis suppression might increase the risk of ONJ in NBPs users. We performed a multicenter retrospective study and reviewed literature data to assess the occurrence and to investigate the nature of ONJ in RCC patients taking NBPs and targeted agents. Nine Italian Centers contributed to the data collection. Patients with exposed and nonexposed ONJ were eligible for the study if they had been taking NBPs and were receiving targeted agents at the time of ONJ diagnosis. Forty-four RCC patients were studied. Patients were mostly male (82%), with a median age of 63 years (range, 45-85 years). Zoledronic acid (93%) and sunitinib (80%) were the most frequently used NBP and antiangiogenic agent, respectively. Other agents included Pamidronate, ibandronate, sorafenib, bevacizumab, mammalian target of rapamycin inhibitors. Forty-nine sites of ONJ were encountered, with the mandible being the preferred site of ONJ (52%); both jaws were affected in 5 cases (12%). The most common precipitating event was dental/periodontal infection (34%), followed by tooth extraction (30%). Oral triggers of ONJ were missing in 10 cases (23%). This unexpectedly high number of ONJ cases, in comparison with literature data, suggests that frequency of ONJ in RCC patients might be largely underestimated and suggests a potential role for targeted agents in the incremental risk of ONJ.

Preventive strategies and clinical implications for bisphosphonate-related osteonecrosis of the jaw: a review of 282 patients.

OBJECTIVE: To describe and evaluate the effectiveness of oral and dental prevention strategies for cancer patients who were about to begin bisphosphonate (BP) intravenous therapy with zoledronate. METHODS: Patients were divided into 2 groups according to their history with BPs: group PA (preventive approach) and group OB (observation). Group PA patients had never been previously treated with BPs, and group OB patients had already undergone therapy with BPs. All patients received a complete oral and dental examination and had a panoramic radiograph. If necessary, oral hygiene, and restorative and rehabilitation therapy were offered to patients. All patients participated in regular checkups every 6 months. Group PA patients underwent oral surgical procedures, as needed. RESULTS: A total of 282 patients (162 women, 120 men) were included in this analysis (PA: n = 217; OB: n = 65). In group OB, 4.6% of patients presented with osteonecrosis of the jaw (ONJ) at first visit and 10.8% developed new ONJ during the 18-month follow-up period. No patients in group PA had ONJ. Anti-angiogenic therapy was associated with ONJ (p < 0.01) and patients with a higher number of zoledronate infusions were significantly more likely to develop ONJ (p < 0.01). CONCLUSION: Although the incidence of BP-related ONJ is fairly low, it remains a painful and difficult complication to treat. An interdisciplinary preventive approach is essential to prevent and manage this condition.