Precision-guided therapy in H3K27-altered diffuse midline glioma

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.