BRAF fusion

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

P2, N=23, Terminated, Day One Biopharmaceuticals, Inc. | Phase classification: P1/2 --> P2 | N=168 --> 23 | Active, not recruiting --> Terminated; Sponsor decision

This dual alteration necessitates multimodal therapeutic approaches targeting both pathways. This case emphasizes the importance of integrated diagnostics in glioma classification and personalized treatment, with further research needed to explore the implications of such rare co-occurrences.

This study demonstrated the robustness of FoundationOne®RNA and supports its use as a supplement to tissue DNA comprehensive genomic profiling (CGP) in routine clinical practice. Additional work is required to clarify optimal clinical scenarios for fusion detection and enable gene expression biomarkers for clinical use.

P1, N=109, Terminated, MapKure, LLC | Active, not recruiting --> Terminated; The study was terminated by the sponsor for reasons unrelated to safety.