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Contrahemispheric Cortex Predicts Survival and Molecular Markers in Patients With Unilateral High-Grade Gliomas.

ABSTRACT: Background: Malignant high-grade gliomas are characterized by infiltration and destruction of surrounding brain tissue. Alterations in the contrahemispheric brain structure and their roles that may offer prognostically valuable information have not been investigated in high-grade gliomas. Methods: In total, 153 patients with unilateral glioma (low-grade, n = 77; high-grade, n = 76) and 115 healthy controls (HCs) were recruited and scanned with 3-D T1 imaging. The gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volume in the contrahemisphere were examined. Partial correlation, logistic regression, and multivariate Cox's regression analyses were performed. Results: The contrahemispheric GM volume (CHGMV) in the high-grade glioma patients was significantly decreased compared to that in the HCs/low-grade gliomas (one-way ANOVA, Bonferroni corrected, p < 0.05). The CHGMV is significantly correlated with the WHO grade (r = -0.22, p < 0.05) and contrast-enhanced volume (r = -0.33, p < 0.01). In the high-grade gliomas, the binary logistic regression revealed that the CHGMV can independently predict isocitrate dehydrogenase 1 (IDH1) and P53 mutations. The survival curves revealed that the patients with a low CHGMV had a shorter overall survival (OS) than the patients with a high CHGMV (p = 0.001). The multivariate Cox's regression analysis showed that a low CHGMV can independently predict unfavorable OS with a hazard ratio of 2.883 (p = 0.035). Conclusions: Volume of the contrahemispheric cortex can be potentially used in clinical practice as an imaging biomarker to predict survival and molecular markers in patients with unilateral high-grade gliomas.

SUBMITTER: Yuan T

PROVIDER: S-EPMC7390929 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Contrahemispheric Cortex Predicts Survival and Molecular Markers in Patients With Unilateral High-Grade Gliomas.

Yuan Taoyang T Ying Jianyou J Zuo Zhentao Z Jin Lu L Gui Songbai S Gao Zhixian Z Li Guilin G Wang Rui R Zhang Yazhuo Y Li Chuzhong C

Frontiers in oncology 20200723

Background: Malignant high-grade gliomas are characterized by infiltration and destruction of surrounding brain tissue. Alterations in the contrahemispheric brain structure and their roles that may offer prognostically valuable information have not been investigated in high-grade gliomas. Methods: In total, 153 patients with unilateral glioma (low-grade, n = 77; high-grade, n = 76) and 115 healthy controls (HCs) were recruited and scanned with 3-D T1 imaging. The gray ...[more]

PMID: 32793462

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Project description:Bithalamic gliomas are rare cancers diagnosed based on poorly defined radiologic criteria. Infiltrative astrocytomas account for most cases. While some previous studies reported dismal outcomes for patients with bithalamic gliomas irrespective of therapy and histologic grade, others described better prognoses even without anticancer therapy. Little is known about their molecular characteristics. We reviewed clinical, radiologic, and histologic features of patients with bithalamic gliomas treated at our institution over 15 years. Targeted sequencing of mutational hotspots in H3F3A, HIST1H3B, IDH1/2, and BRAF, and genome-wide analysis of DNA methylation and copy number abnormalities was performed in available tumors. Eleven patients with bithalamic gliomas were identified. Their median age at diagnosis was 4.8 years (range: 1-15.7). Additional involvement of the brainstem, basal ganglia, and cerebral lobes occurred in 11, 9, and 3 cases, respectively. All patients presented with hydrocephalus. Two-thirds of the patients had a histologic diagnosis of anaplastic astrocytoma. Despite aggressive therapy, our youngest patient, the only one diagnosed before 1 year of age, is the sole long-term survivor. DNA methylation could be performed in seven tumors, all of which clustered with the RTK I 'PDGFRA' subgroup by unsupervised hierarchical analysis of methylation array against a previously published cohort of 59 pediatric high-grade gliomas. Sequencing of hotspots mutations could be done in 10 tumors, none of which harbored H3F3A p.K27 and/or the respective DNA methylation signature, and any other hotspot mutations. Amplification of MDM4 (n = 2), PDGFRA (n = 2), and ID2 combined with MYCN (n = 1) were observed in 7 tumors available for analysis. In comparison with the previously published experience with unilateral high-grade thalamic astrocytomas where H3F3A p.K27 was present in two-thirds of cases, the absence of this molecular subgroup in bithalamic gliomas was striking. This finding suggests that unilateral and bithalamic high-grade gliomas may represent two distinct molecular entities.

Project description:BackgroundThe radiation dose for patients with low-grade gliomas (LGGs) is controversial. The objective of this study was to investigate the impact of the radiation dose on survival for patients with LGGs and especially for molecularly defined subgroups.MethodsThree hundred fifty-one patients with newly diagnosed LGGs from the multicenter Chinese Glioma Cooperative Group received postoperative radiotherapy (RT) in 2005-2018. The RT dose, as a continuous variable, was entered into a Cox regression model using penalized spline regression to allow for a nonlinear relationship between the RT dose and overall survival (OS) or progression-free survival (PFS). Inverse probability of treatment weighting (IPTW)-adjusted propensity scores were used to correct for potential confounders. Dose effects on survival within IDH mutation and 1p/19q codeletion defined subgroups were analyzed.ResultsThe risk of mortality and disease progression decreased sharply until 54 Gy. High-dose RT (≥54 Gy) was associated with significantly better 5-year OS (81.7% vs 64.0%; hazard ratio [HR], 0.33; P < .001) and PFS (77.4% vs 54.5%; HR, 0.46; P < .001) than low-dose RT (<54 Gy). IPTW correction confirmed the associations (HR for OS, 0.44; P = .001; HR for PFS, 0.48; P = .003). High-dose RT was associated with longer PFS (HR, 0.25; P = .002; HR, 0.21; P = .039) and OS (HR, 0.27; P = .006; HR, 0.07; P = .017) in IDH-mutant/1p/19q noncodeleted and IDH wild-type subgroups, respectively. No significant difference in survival was observed with high-dose RT in the IDH-mutant/1p/19q codeleted subgroup.ConclusionsHigh-dose RT (≥54 Gy) was effective in LGGs. Patients with an IDH mutation/1p/19q noncodeletion or IDH wild-type may need to be considered for high-dose RT.Lay summaryThe radiotherapy dose-response was observed in patients with low-grade gliomas, and high-dose radiotherapy (≥54 Gy) was associated with improved survival. Patients with an IDH mutation/1p/19q noncodeletion or wild-type IDH may have improved survival with the administration of high-dose radiotherapy.

Dataset Information

Contrahemispheric Cortex Predicts Survival and Molecular Markers in Patients With Unilateral High-Grade Gliomas.

Publications

Contrahemispheric Cortex Predicts Survival and Molecular Markers in Patients With Unilateral High-Grade Gliomas.

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