BRAF fusion

High [18F] Fluciclovine uptake in pilocytic astrocytoma may reflect amino acid transporter expression, which may lead to overestimation of the WHO grade. Awareness of this pitfall is essential in pediatric neuro-oncology.

Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.

The patient with EML4::ALK fusion was treated with alectinib with partial response...These finding further suggest that SMARCA4d-UT and carcinomas with SMARCA4 loss may be on the same spectrum of disease, and accurate histologic distinction between these lesions may be challenging. A unified terminology may be beneficial for appropriate diagnosis and treatment.

Assessment with green chemistry tools yielded favourable eco-scores (ComplexMoGAPI 90, AGREE 0.61, BAGI 70, RAPI 92.5, EVG Q2, and RGBfast 97.5%). This validated RP-UPLC procedure offers reliable, sensitive, and sustainable Tovorafenib analysis, supporting both efficient pharmaceutical quality control and environmental sustainability.

MM arising within CGMN poses diagnostic and therapeutic challenges. While molecular and epigenomic profiling supports accurate classification and understanding of disease biology, the role of immunotherapy remains uncertain-marked by reduced efficacy and significant immune-related toxicity. A multidisciplinary approach is essential to guide management and improve outcomes in this rare pediatric malignancy.

The best-performing model achieved an average one-vs-the-rest area under receiver operating characteristic curve of 0.819 (95% confidence interval [0.791, 0.848]). This study highlights the potential of radiomics-based ML models for molecular subtype differentiation in pLGG, with per-patient predictions enabling outlier identification and subgroup performance evaluation.

Our model using simple and widely available variables for all clinicians shows an adequate predictive model with strong discriminatory power for BRAF fusion tumors versus others.

Our results suggest that national rounds with centralized molecular review can direct AYA patients with CNS tumors toward targeted agents and clinical trials, while deferring radiation therapy. Taken together, our work details an ongoing effort to improve and standardize care of AYA patients with CNS tumors in Canada.

We report that most tumors in this series arose in adult patients and lacked Spitz-like microscopic features. Awareness of the varied clinical and histopathologic presentation of RAF1 and BRAF fusion-positive melanomas is important as the protein products of these kinase gene fusions constitute potentially actionable therapeutic targets.

P1/2, N=105, Completed, Children's Hospital Los Angeles | Active, not recruiting --> Completed | Trial completion date: Nov 2023 --> Aug 2025