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. 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. 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). 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.
Wang et al. (2026) studied this question.