Prevalence of BRAFV600 in glioma and use of BRAF Inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review. Neuro-oncology, [noab247].

Background This study aims to determine if the intravitreal dexamethasone implant (DEX implant, Ozurdex; Allergan, Inc., Irvine, California) is effective for treating intermediate, posterior, and panuveitis as a monotherapy or adjunctive treatment to systemic immunomodulatory therapies. Methods A systematic review using MEDLINE, EMBASE, and PubMed database searches was conducted with the Oxford Centre for Evidence-based Medicine Levels of Evidence criteria to select publications. Available background information and patient data from each study was tabulated. Outcomes studied were central retinal thickness (CRT), best corrected visual acuity, intraocular inflammation (anterior chamber cells, vitreous haze), number of patients with prior and concomitant immunomodulatory treatments, intraocular pressure (IOP) elevation (≥ 25 mmHg), and other adverse effects associated with the implant. Results One hundred ninety-five (61.51%) patients had previous immunomodulatory treatment while 232 (64.8%) were treated with concomitant immunomodulatory therapy with the DEX implant. CRT decreased by an average of 198.65 μm (42.74%). Visual acuity improved to an average of 0.451 (logMAR) or 20/57 (Snellen) which is a 43.11% improvement from baseline. One hundred seventy-three (59%) of eyes were quiescent at the end of the trials, of which 40 (13.7%) previously inflamed eyes became quiescent. Elevated IOP occurred in 91 (20.6%). The most common adverse events were cataract/posterior subcapsular opacities in 47 (11.03%) patients and conjunctival hemorrhage in 24 (5.44%) patients. Conclusions The DEX implant is an effective medication for the treatment of posterior segment uveitis, uveitic macular edema, and results in improved visual acuity. Development of elevated IOP and cataract should be closely monitored as they are tangible risks associated with the DEX implant. This study was not able to determine whether the DEX implant was more effective as a monotherapy or as an adjunctive therapy to systemic immunomodulatory treatment.

Background The V600mutation in the v-raf murine sarcoma oncogene homologue B1 (BRAF) enzyme, is a potential clinically actionable target in gliomas. BRAF inhibitors are in wide clinical use for other tumour types, particularly melanoma. The prevalence of this mutation across all gliomas is not fully elucidated and is needed to inform potential screening and treatment. Methods A systematic review using articles on the MEDLINE and EMBASE databases (February 1, 2019) was carried out. A meta-analysis was conducted to calculate the prevalence of BRAF mutations in patients with gliomas across all populations and age groups in a clinical setting. Preliminary Results The review identified 75 studies including 6316 patients; the ages of participants ranged from 30 days to 90 years with a mean age of 32.75 years. Across all studies, the average prevalence of BRAF mutations was 16% (95% confidence interval (CI) from 12% to 20%) but estimates were highly variable across studies, ranging from 0% to 78%. The average prevalence of BRAF mutations in paediatric group was 15% (95% CI 10% to 20%) while the average prevalence in the adult group was 9% (95% CI 4% to 16%). Low grade gliomas had an average prevalence of 19% (95% CI 14% to 25%) compared with 7% (95% CI 4% to 11%) in high-grade gliomas. Conclusions BRAF mutations were found to be more prevalent in pediatric patients and in low grade gliomas. Screening these patients for BRAF mutations and treating them with BRAF inhibitors represents a promising area of future medical practice.