Prognostic Utility of Age Stratification and Radiotherapy Dosage in Pediatric Diffuse Midline Gliomas, H3 K27-altered

Introduction: Diffuse midline gliomas, H3 K27-altered (DMG) are rare, grade 4 tumors localized to the diencephalon, brainstem, and cervical spine. DMGs, characterized by a K27M missense mutation in histone H3, are often not surgically debulked and predominantly present with poor outcomes in children. Prognostic factors and treatment management of DMGs—including the optimal use of radiotherapy—need to be further elucidated due to the rarity of the lesions. Herein, we describe the clinical outcomes of DMG patients at our institution.

Methods: Pediatric patients ( < 18 y/o) between 2015 and 2023 with biopsy-proven DMG were reviewed. Demographic, treatment, and tumor characteristics (histologic and molecular) were recorded. Progression free survival (PFS) and overall survival (OS) were calculated according to the Kaplan Meier-method. Multivariate regression analyses were performed.

Results: Twenty patients were included (median age=8.5 y/o), and overall PFS and OS at 12 months were 20% and 39% respectively. At diagnosis, patients < 10 y/o (n=13) experienced significantly decreased PFS and OS compared to patients ≥10 years y/o (n=7); PFS and OS at 12 months was 43% and 71% for ≥10 y/o patients versus 8% and 23% for < 10 y/o patients (p < 0.01). Patients that received >54Gy cumulative radiation due to re-irradiation for progressive disease (mean=84Gy, n=9) had an OS of 67% at 12 months, which was significantly greater than an OS of 18% at 12 months (p≤0.05) for patients that received ≤54Gy and no re-irradiation (mean=53Gy, n=11). Age at diagnosis and radiation dosage were independent predictors of OS (age:p≤0.05, radiation:p≤0.01).

Conclusion : We present a pediatric cohort that demonstrates increased survival in DMGs that present at ≥10 y/o compared to < 10 y/o and a potential survival benefit in delivering >54Gy of radiation. Our institutional experience suggests considering re-irradiation for progressive pediatric DMGs, especially in patients < 10 y/o, while factoring in the risk of post-radiotherapy sequelae.