Background: H3K27M-mutant diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brainstem tumor with a median overall survival (OS) of less than one year. Radiotherapy (RT) is the standard treatment, but the survival benefit of adding temozolomide (TMZ) remains controversial.
Methods: Two retrospective cohorts were analyzed. In the single-center cohort (44 patients), patients were divided into three groups: RT alone (n = 16), Stupp regimen (concurrent and adjuvant TMZ, n = 15), and RT followed by sequential TMZ (RT→TMZ, n = 13). In the SEER database cohort (39 patients), patients were divided into RT alone (n = 19) and chemoradiotherapy (CRT, n = 20). Survival was analyzed using the Kaplan-Meier method, log-rank test, and Cox regression.
Results: In the single-center cohort, no significant differences were observed among the three groups in objective response rate (ORR; P = 0.693), disease control rate (DCR; P = 1.000), median progression-free survival (PFS; 6, 7, and 8 months, respectively; P = 0.621), or median OS (11, 13, and 13 months, respectively; P = 0.534). The Stupp group had significantly higher rates of leukopenia and liver function impairment than the RT group (P < 0.05), with a trend toward more grade ≥ 3 adverse events (AEs). No significant difference in AEs was seen between RT→TMZ and RT. In the SEER cohort, median OS was 11 months in both groups (P = 0.582); median disease-specific survival (DSS) was 11 and 12 months, respectively (P = 0.585).
Conclusion: Adding TMZ to RT whether (concurrent/adjuvant or sequential) does not significantly improve PFS or OS in H3K27M-mutant DIPG patients. The Stupp regimen significantly increases hematological and hepatic toxicity.
Keywords: Chemotherapy; Diffuse intrinsic pontine glioma; H3K27M mutation; Radiotherapy; SEER database; Temozolomide.
© 2026. The Author(s).