Dataset Information

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

ABSTRACT:

Introduction

Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs.

Methods

We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression.

Results

A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs.

Conclusions

In this study, MI-positive cases had a worse prognosis compared with MI-negative cases.

Previous presentations

No portion of this study has been presented or published previously.

SUBMITTER: Kegoya Y

PROVIDER: S-EPMC10978637 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

Kegoya Yasuhito Y Otani Yoshihiro Y Inoue Yohei Y Mizuta Ryo R Higaki Fumiyo F Washio Kana K Koizumi Shinichiro S Kurozumi Kazuhiko K Ishida Joji J Fujii Kentaro K Yamamoto Norio N Tanaka Yoshihiro Y Date Isao I

Journal of neuro-oncology 20240301 1

<h4>Introduction</h4>Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findin ...[more]

PMID: 38427132

Similar Datasets

Project description:BackgroundDiffuse hemispheric glioma H3 G34-mutant (G34-DHG) is a new type of pediatric-type diffuse high-grade glioma in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The current treatment for G34-DHG involves a combination of surgery and conventional radiotherapy or chemotherapy; however, the therapeutic efficacy of this approach is not satisfactory. In recent years, molecular targeted therapy and immunotherapy have achieved significant benefits in a variety of tumors. In-depth understanding of molecular changes and immune infiltration in G34-DHGs will help to establish personalized tumor treatment strategies. Here, we report the clinicopathological, molecular and immune infiltration characteristics of G34-DHG cases from our center along with cases from the HERBY Trial and the Chinese Glioma Genome Atlas database (CGGA).MethodsHematoxylin-eosin (HE) and immunohistochemistry (IHC) staining were used to present the clinicopathological characteristics of 10 Chinese G34-DHG patients treated at our institution. To address the molecular characteristics of G34-DHG, we performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) analyses of 5 patients from our center and 3 Chinese patients from the Chinese Glioma Genome Atlas (CGGA) database. Additionally, 7 European G34-DHG patients from the HERBY Trail were also subjected to analyses, with 7 cases of WES data and 2 cases of RNA-seq data. Six G34-DHG patients from another organization were used as external validation.ResultsWES showed a high frequency of PDGFRA mutation in G34-DHGs (12/15). We further identified frequent mutations in MUC family genes in G34-DHGs, including MUC16 (8/15) and MUC17 (8/15). Although no statistical difference was found, PDGFRA mutation tended to be an indicator for worse prognosis whereas MUC16/MUC17 mutation indicated a favorable prognosis in G34-DHGs. RNA sequencing results revealed that most G34-DHG are considered to be immune cold tumors. However, one patient in our cohort with MUC16 mutation showed significant immune infiltration, and the total overall survival of this patient reached 75 months.ConclusionsOur results demonstrate that G34-DHG is a new high-grade glioma with high frequency of PDGFRA and MUC gene family mutations. PDGFRA may serve as an indicator of poor prognosis and an effective therapeutic target. Moreover, MUC16 tends to be a favorable prognostic factor and indicates high immune infiltration in certain patients, and these findings may provide a new direction for targeted therapy and immunotherapy of patients with G34-DHGs.

Project description:Diffuse hemispheric glioma H3 G34-mutant (DHG) has been identified as a distinct pediatric-type high-grade glioma, according to the World Health Organization (WHO) classification of central nervous system tumors. Widely accepted treatment options include surgery, radiation, and conventional chemotherapy. However, the efficacy of the surgical resection remains unclear. Although there are some reports, a comprehensive understanding of the clinical characteristics, pathogenesis, and outcomes of DHG is insufficient to evaluate the efficacy of maximal tumor resection. We retrospectively analyzed nine cases of DHG, focusing on imaging features and progression patterns. Initial Magnetic Resonance Imaging (MRI) revealed T2/FLAIR high lesions with minimal or no contrast enhancement in all cases. The lesions exhibited T2/FLAIR hyperintensities and focal diffusion restriction in the deep white matter, with most showing high methionine accumulation, suggesting deep white matter infiltration at the time of diagnosis. The extent of white matter infiltration in tumor resection cases was significantly negatively correlated with the extent of resection (EOR). In addition, cases with EOR of 90% or more had significantly longer progression-free survival (PFS) and overall survival (OS). However, achieving an EOR of 90% or more was possible in fewer than half of the cases, primarily in those with relatively limited white matter involvement. Histopathological findings of the tumor obtained by initial resection and autopsy revealed extensive deep white matter infiltration, with one patient demonstrating tumor invasion into the brainstem at death. Our study highlights early deep white matter infiltration of DHGs, complicating surgical resection, and potentially contributing to a poor prognosis. While EOR may influence survival to some extent, residual lesions extensively infiltrate the white matter and eventually invade the brainstem and contralateral brain, thereby contributing to mortality. These findings underscore the challenges of managing DHGs and emphasize the need for further research on effective therapeutic strategies, particularly to understand and target their unique progression patterns.

Dataset Information

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

Introduction

Methods

Results

Conclusions

Previous presentations

Publications

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets