Precision-guided therapy in H3K27-altered diffuse midline glioma

Area of Science:

• Pediatric Oncology
• Molecular Diagnostics
• Clinical Trials

Background:

• High-risk pediatric cancers, including diffuse midline glioma (DMG), have limited treatment options.
• Precision-guided therapy (PGT) has improved survival in some pediatric cancers, but its efficacy in DMG is not well-established.

Purpose of the Study:

• To evaluate the feasibility and clinical benefit of PGT in children with H3K27-altered diffuse midline glioma (DMG).
• To assess survival outcomes in DMG patients receiving PGT within the Australian PRSIM clinical trial.

Main Methods:

• Prospective cohort study enrolling 68 pediatric DMG patients in the PRSIM trial (NCT03336931).
• Comprehensive molecular profiling including whole genome sequencing (WGS) and RNAseq was performed.
• PGT recommendations were provided, and survival analysis was conducted for eligible patients.

Main Results:

• PGT was recommended for 74% of patients; 26% received PGT, with an overall response rate of 48%.
• Patients receiving PGT after tumor progression showed significantly improved overall survival (p=0.007) and progression-free survival (p=0.001).
• Median overall survival was 21.3 months for the PGT group versus 12.1 months for the non-PGT group.

Conclusions:

• Precision-guided therapy is feasible in pediatric patients with diffuse midline glioma.
• PGT demonstrates potential clinical benefit, particularly for patients treated after tumor progression, improving survival outcomes.