Re-Irradiation in Pediatric Diffuse Midline Glioma: A Multi-Institutional Retrospective Study

Children with recurrent diffuse midline gliomas (DMGs) have limited therapeutic options at recurrence. Re-irradiation (RT2) may be used at progression, but with uncertainty about the benefit.

We conducted a multi-institutional retrospective study of children aged < 18 with DMG treated at three centers (Toronto, Canada; Birmingham, UK; Nottingham, UK). Patients with radiologic progression after the first radiation (RT1) were included. Overall survival (OS) was calculated from the date of progression after RT1. Survival was analyzed using the Kaplan-Meier method. Multivariable Cox regression identified independent predictors of OS.

A total of 167 patients were included with a median age of 7.9 years; 54 (32%) received RT2. Children selected for RT2 had a longer interval from RT1 to progression (0.79 vs. 0.52 years, p < 0.0001). Median OS from progression was longer in the RT2 group (0.59 years) compared to the no RT2 cohort (0.21 years; p < 0.0001). Six-month OS was 68% versus 16%, and 1-year OS was 19% versus 3%, respectively. Patients needing RT2 ≥ 1 year after RT1 had superior survival compared with earlier RT2 (0.81 vs. 0.42 years; p = 0.0041). Higher RT2 dose (≥30.6 Gy) showed a non-significant trend towards longer OS (p = 0.086). In multivariable analysis, use of RT2 was the strongest independent predictor of survival (HR 0.29, 95% CI 0.20-0.42; p<0.0001).

In this large, multi-institutional international cohort, children with DMG treated with re-irradiation at progression showed a survival benefit, supporting re-irradiation as a key component of salvage therapy.