Efficacy and Toxicity of Bevacizumab in Children with NF2-Related Schwannomatosis: A Systematic Review.

Background/objectives: NF2-related schwannomatosis (NF2) is a tumor predisposition syndrome that typically presents with bilateral vestibular schwannomas, together with other intracranial and spinal schwannomas, meningiomas, and/or ependymomas. Bevacizumab, a VEGF inhibitor, has the potential to decrease schwannoma volume and improve hearing in adults, but the literature on the effects in children is sparse. This narrative review aims to evaluate the use of bevacizumab in pediatric NF2 patients, focusing on hearing, tumor progression, and toxicity.

Methods: A literature review was conducted following PRISMA guidelines. Articles were searched in PubMed, Embase, Web of Science, Cochrane Library, Emcare, and Academic Search Premier on 18 July 2024. Inclusion criteria were patients ≤ 18 years, diagnosed with NF2 and treated with bevacizumab. Two authors independently assessed the quality of the evidence and extracted relevant data from the included articles.

Results: Seventeen articles including 62 pediatric NF2 patients met the inclusion criteria. Studies varied widely in treatment regimens and outcome parameters. Tumor regression was reported in 6/56 patients (11%) and 38/56 (68%) remained stable. Hearing improved in 15/45 patients (33%) and did not further deteriorate in 27/45 (60%). An improvement in other symptoms was seen in 6/29 patients (28%). Toxicity was reported in five studies, documenting 13 adverse events in 28 patients ranging from grade 1 to grade 3. Treatment was discontinued in both patients who experienced grade 3 toxicity.

Conclusions: Bevacizumab seems to be a viable treatment option for pediatric NF2 patients. Tumor regression or stabilization is achieved in the majority of patients (77%). Moreover, a considerable number of pediatric patients experience hearing stabilization or improvement (93%). Bevacizumab appears to be relatively well tolerated, offering a non-invasive therapeutic option for children with NF2 suffering from progressive vestibular schwannomas and hearing loss.