Second-Course Reirradiation Versus No Reirradiation in Pediatric Diffuse Intrinsic Pontine Glioma: A Meta-Analysis of Survival Outcomes.
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BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) presents in 1-2 cases per million children annually. Upfront radiation therapy (RT) is the only proven treatment for DIPG despite which relapse is common. Survival benefits of reirradiation (reRT) have been studied priorly in a smaller, single-arm meta-analysis, but our study is the first comparing reRT versus single-course RT. METHODS: Our study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search was conducted through PubMed, Medline, ScienceDirect, and Cochrane Library up to June 21, 2025. Quality assessment was done using the Newcastle Ottawa Scale. Overall survival (OS) from diagnosis, progression-free survival (PFS) from first radiation, one-year OS, and postprogression OS were analyzed. A random-effects model was used on RevMan 5.4.1 with heterogeneity assessed via I2, and statistical significance set at P < 0.05. RESULTS: Seven retrospective cohort studies (597 pediatric DIPG patients) were included. Of these, 236 patients received reRT, and 361 received only initial RT. Pooled analysis found that OS from diagnosis showed a significant benefit with reRT with a standardized mean difference of 1.35 (95% confidence interval: 0.80-1.91; P < 0.00001). One-year OS also significantly favored reRT (risk ratio: 1.89; 95% confidence interval: 1.28-2.79; P = 0.001). PFS showed a nonsignificant trend favoring re-RT (standardized mean difference: 0.32; P = 0.10). CONCLUSIONS: OS significantly improved with reRT; however, PFS from initial treatment showed no statistically significant difference between groups. Despite improved OS, reRT in DIPG lacks standardized protocols and targeted studies with patient-reported outcomes and time-to-symptom progression are needed to validate if survival benefits of reRT for DIPG are clinically significant.