Abstract C015: Clinicogenomic characterization of diffuse hemispheric glioma presenting pre-operatively with tumor-associated bleeding
Nikhil Joshi, Patrick J. Beck, Rakesh Murugesan, Sina Bagheri, Ezra Beaubien, Natalie Mamaril, Sreehita Hajeebu, Ali Nabavizadeh, Cassie Kline, Peter Madsen, Jessica B. FosterAbstract
Background:
Pediatric diffuse hemispheric glioma (DHG) is a histone-mutated (H3.3G34R/V) high-grade glioma with poor prognosis. Clinical observation and prior reports identify that some patients with H3-mutated DHG can present with tumor-associated bleeding. Here, we sought to identify clinical and molecular characteristics predictive of bleeding risk in this tumor population.
Methods:
Clinical data was obtained through chart review after de-identification by the Children’s Brain Tumor Network in accordance with the institutional review board. Presence of blood products was determined on preoperative magnetic resonance imaging (MRI) by a board certified pediatric neuroradiologist. Molecular data was abstracted through The Open Pediatric Cancer Project (OpenPedCan). Transcriptomic and genomic analyses were completed in R 4.3.1 using edgeR, msigdbr, and xCell.
Results:
15 patients with H3-mutant DHG were identified at our institution. Six presented with acute intraparenchymal hemorrhage, while five had evidence of intratumoral blood products on pre-operative MRI. Four patients showed no pre-operative evidence of tumor-associated bleeding. No significant differences in clinical characteristics were observed between patients presenting with or without bleeding; however, patients presenting with bleeding demonstrated a trend toward shorter overall and progression-free survival. Bulk transcriptomic data was available for ten (67%) of these patients, six from the bleeding cohort and all four without. Increased expression of VEGFA (log fold change [LFC]: 3.45, p = 2E-07) and CA9 (LFC: 5.97, p = 8E-05) was seen in patients with tumor-associated bleeding. From a cohort of 34 H3-mutant DHGs from OpenPedCan, 11 samples with high expression (AngioHi) and 11 samples with low expression (AngioLo) of both VEGFA and CA9 (AngioHi) were compared. AngioHi samples demonstrated preferentially higher IL8 expression (LFC: 3.56, p = 0.01) with expression patterns suggestive of increased tumor-associated macrophage populations. Alterations to PTEN, FBXW7, and PDGFRA were more frequently observed in the AngioHi cohort.
Conclusions:
We suggest survival, transcriptional, and mutational differences for pediatric DHG patients presenting with tumor-associated bleeding. These data can inform future, larger-scale studies, which will be necessary to confirm the validity of these findings and investigate the potential for targeted therapeutics. Additional work is ongoing to determine if these patterns are generalizable across other pediatric high-grade glioma subtypes presenting with tumor-associated bleeding.
Citation Format:
Nikhil Joshi, Patrick J. Beck, Rakesh Murugesan, Sina Bagheri, Ezra Beaubien, Natalie Mamaril, Sreehita Hajeebu, Ali Nabavizadeh, Cassie Kline, Peter Madsen, Jessica B. Foster. Clinicogenomic characterization of diffuse hemispheric glioma presenting pre-operatively with tumor-associated bleeding [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Bridging Discovery and Clinical Impact in Pediatric Cancer; 2026 Sep 22-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_1):Abstract nr C015.