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Updated: May 21, 2026
Live-3D-Cell Immunocytochemistry Assays of Pediatric Diffuse Midline Glioma
Published on: November 11, 2021
Precision-guided therapy in H3K27-altered diffuse midline glioma
Campbell J L McKay1,2, Chelsea Mayoh3,4, Phoebe Power5
1The Royal Children's Hospital, Melbourne, VIC, Australia.
Abstract:
Precision-guided therapy (PGT) approaches have shown improved survival in children with high-risk cancer, but it is unclear whether children with H3K27-altered diffuse midline glioma (DMG) benefit from this approach. Here we report on the cohort of patients with DMG who were consecutively enroled in the Australian Childhood Cancer PRecISion Medicine for Children with Cancer (PRSIM) clinical trial (NCT03336931), a prospective cohort study aimed at providing PGT recommendations based on comprehensive molecular profiling. A total of 68 patients with DMG were enroled and 58 (85%) had WGS and RNAseq performed. PGT was recommended for 50 patients (74%). Eighteen patients (26%), who received 21 PGTs, were eligible for survival analysis. The overall response rate (CR or PR) was 48% (n = 10). Median overall survival for the PGT group was 21.3 months versus 12.1 months for those that did not receive PGT (p = 0.34). Patients who received PGT after tumor progression had significantly improved overall survival (p = 0.007) and subsequent progression-free survival (p = 0.001) compared to those that received unguided therapy or reirradiation alone. These results highlight the feasibility of a precision-guided approach and demonstrate its potential clinical benefit in patients with DMG.
Insights
Precision-guided therapy (PGT) shows promise for children with diffuse midline glioma (DMG). PGT improved survival outcomes, especially after tumor progression, highlighting its clinical benefit in this high-risk pediatric cancer.
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.
