The gut microbiome in pediatric diffuse midline gliomas: Correlative study results from the PNOC022 trial
Abstract
10015
Background:
The gut microbiome exerts a multifaceted influence on treatment outcomes across various cancers, yet its potential role in diffuse midline gliomas (DMGs) remains under-explored. In this report, we present the gut microbiome findings from cohort 2 in the DMG–Adaptive Combination Trial (DMG-ACT, PNOC022).
Methods:
PNOC022 is an open-label, multi-institutional, international clinical trial using a Bayesian drug combination platform trial design. This report focuses on the combination therapy arm involving dordaviprone and paxalisib, administered to patients (aged 2–39 years) who had completed standard-of-care radiation therapy (Cohort 2). Stool samples were collected at baseline (n = 22), cycle 1 day 1 (n = 15), cycle 7 day 1 (n = 9), and at progression (n = 4). Microbiome profiling was performed with shotgun metagenomic sequencing (NovaSeq X Plus Series, PE150). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Longitudinal shifts in microbial communities were evaluated using α-diversity (Shannon-index) and β-diversity (Bray-Curtis dissimilarity index). Baseline α-diversity associations with PFS and OS were examined with log-rank tests and further validated through age-adjusted Cox regression analysis.
Results:
Between November 2021 and October 2023, 69 biopsy-confirmed DMG patients enrolled (median age 9 years [range 3-37], n = 42 female [61%]) in cohort 2. Median OS from time of diagnosis was 15.6 months…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 42 participants or records.
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