Dataset Information

Image Analysis Reveals Microstructural and Volumetric Differences in Glioblastoma Patients with and without Preoperative Seizures.

ABSTRACT: Purpose: Seizures related to tumor growth are common in glioma patients, especially in low-grade glioma patients this is often the first tumor manifestation. We hypothesize that there are associations between preoperative seizures and morphologic features (e.g., tumor size, location) and histogram features in patients with glioblastoma (GB). Methods: Retrospectively, 160 consecutive patients with initial diagnosis and surgery of GB (WHO IV) and preoperative MRI were analyzed. Preoperative MRI sequences were co-registered (T2-FLAIR, T1-contrast, DTI) and tumors were segmented by a neuroradiologist using the software ITK-snap blinded to the clinical data. Tumor volume (FLAIR, T1-contrast) and histogram analyses of ADC- and FA-maps were recorded in the contrast enhancing tumor part (CET) and the non-enhancing peritumoral edema (FLAIR). Location was determined after co-registration of the data with an atlas. Permutation-based multiple-testing adjusted t statistics were calculated to compare imaging variables between patients with and without seizures. Results: Patients with seizures showed significantly smaller tumors (CET, adj. p = 0.029) than patients without preoperative seizures. Less seizures were observed in patients with tumor location in the right cingulate gyrus (adj. p = 0.048) and in the right caudate nucleus (adj. p = 0.009). Significant differences of histogram analyses of FA in the contrast enhancing tumor part were observed between patients with and without seizures considering also tumor location and size. Conclusion: Preoperative seizures in GB patients are associated with lower preoperative tumor volume. The different histogram analyses suggest that there might be microstructural differences in the contrast enhancing tumor part of patients with seizures measured by fractional anisotropy. Higher variance of GB presenting without seizures might indicate a more aggressive growth of these tumors.

SUBMITTER: Bette S

PROVIDER: S-EPMC7226080 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Image Analysis Reveals Microstructural and Volumetric Differences in Glioblastoma Patients with and without Preoperative Seizures.

Bette Stefanie S Barz Melanie M Nham Huong Ly HL Huber Thomas T Berndt Maria M Sales Arthur A Schmidt-Graf Friederike F Meyer Hanno S HS Ryang Yu-Mi YM Meyer Bernhard B Zimmer Claus C Kirschke Jan S JS Wiestler Benedikt B Gempt Jens J

Cancers 20200417 4

<i>Purpose</i>: Seizures related to tumor growth are common in glioma patients, especially in low-grade glioma patients this is often the first tumor manifestation. We hypothesize that there are associations between preoperative seizures and morphologic features (e.g., tumor size, location) and histogram features in patients with glioblastoma (GB). <i>Methods</i>: Retrospectively, 160 consecutive patients with initial diagnosis and surgery of GB (WHO IV) and preoperative MRI were analyzed. Preop ...[more]

PMID: 32316566

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Project description:ObjectiveSeizures are a common clinical presentation in patients with glioma and substantially impact patients' quality of life. Hyperhomocysteinemia is defined as abnormally high serum levels of homocysteine (Hcy) and is reportedly linked to susceptibility to various nervous system diseases. However, it remains unclear whether and how hyperhomocysteinemia and its associated genetic polymorphisms promote seizures in glioma patients.MethodsWe retrospectively reviewed all medical data from 127 patients with malignant gliomas, who underwent initial tumor resection by our team between July 2019 and June 2021 and had preoperative measurements of serum Hcy levels. According to whether they had at least one seizure before surgery, they were divided into the seizure and nonseizure groups. We also detected polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and measured intratumoral Hcy levels in these patients.ResultsHyperhomocysteinemia was a susceptibility factor for preoperative seizures in glioma patients according to both univariate analyses (P < 0.001) and multivariate logistic regression analyses (OR 1.239, 95% CI 1.062-1.445, P = 0.007). Patients with the MTHFR C677T variant exhibited elevated serum Hcy levels (P = 0.027) and an increased prevalence of preoperative seizures (P = 0.019). Intratumoral Hcy levels were positively correlated with serum Hcy levels (R = 0.231, P = 0.046) and were elevated in patients with hyperhomocysteinemia (P = 0.031), the MTHFR C677T variant (P = 0.002) and preoperative seizures (P = 0.003). High intratumoral Hcy levels, rather than hyperhomocysteinemia or the MTHFR C677T variant, emerged as an independent risk factor for preoperative seizures (OR 1.303, 95% CI 1.015-1.673, P = 0.038). Furthermore, the effects of hyperhomocysteinemia on epileptic susceptibility were reduced to nonsignificance when intratumoral Hcy was controlled to the same level between groups.SignificanceGlioma patients with hyperhomocysteinemia and the MTHFR C677T variant were susceptible to preoperative seizures, suggesting their potential as biomarkers for the management of seizures in glioma patients. The elevation of intratumoral Hcy is a possible mechanism underlying this susceptibility.

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Project description:Abstract Background: Glioma accounts for around 27% of all primary brain tumors and is responsible for approximately 13,000 cancer-related deaths in the US each year. Glioma tumors can be broadly classified into glioblastoma (GBM) and lower-grade non-GBM. Typically gliomas have a poor prognosis irrespective of medical care, with the most common form, GBM, having a five-year survival rate of only 5%. While genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, individual studies have had limited power to identify risk loci. Methods: We performed the largest GWAS in glioma to date, comprising a meta-analysis of existing GWAS (6,405 cases, 14,100 controls) as well as new GWAS from the Glioma International Case Control Consortium (GICC; 4,572 cases and 3,286 controls) and University of California, San Francisco (UCSF)-Mayo (1,519 cases, 804 controls), totalling 12,496 cases and 18,190 controls. Results: We identified five new loci for GBM at 1p31.3 (rs12752552, near JAK1, P=2.04?×?10–9, odds ratio (OR)=1.22), 11q14.1 (rs11233250, P=9.95?×?10-10, OR=1.24), 16p13.3 (rs2562152, near MPG, P=1.93x10-8, OR=1.21), 16q12.1 (rs10852606, HEATR3, P=1.29?×?10–11, OR=1.18), 22q13.1 (rs2235573, P=1.76?×?10-10, OR=1.15) and eight for non-GBM at 1q32.1 (rs4252707, MDM4, P=3.34?×?10–9, OR=1.19), 1q44 (rs12076373, AKT3, P=2.63?×?10-10, OR=1.23), 2q33.3 (rs7572263, near IDH1, P=2.18?×?10-10, OR=1.20), 3p14.1 (rs11706832, LRIG1l, P=7.66?×?10–9, OR=1.15), 10q24.33 (rs11598018, OBFC1, P=3.39?×?10–8, OR=1.14), 11q21 (rs7107785, P=3.87?×?10-10, OR=1.16), 14q12 (rs10131032, P=5.07x10-11, OR=1.33) and 16p13.3 (rs3751667, P=2.61?×?10–9, OR=1.18). Case-only analyses confirmed the specificity of 11q14.1, 16p13.3 and 22q13.1 associations for GBM and 1q44, 2q33.3, 3p14.1, 11q21 and 14q12 for non-GBM tumors. In the combined meta-analysis, among previously published glioma risk SNPs, those for all glioma at 17p13.1 (TP53), GBM at 5p15.33 (TERT), 7p11.2 (EGFR), 9p21.3 (CDKN2B-AS1) and 20q13.33 (RTEL1) and for non-GBM at 8q24.21 (CCDC26), 11q23.2, 11q23.3 (PHLDB1) and 15q24.2 (ETFA) showed even greater evidence for association. SNPs at 10q25.2 and 12q12.1 for non-GBM tumors retained genome-wide significance (i.e. P<5.0x10-8). Associations at the previously reported 3q26.2 (near TERC) and 12q23.33 (POLR3B) loci for GBM did not retain statistical significance. Conclusions: Our findings substantiate genetic susceptibility to GBM and non-GBM being highly distinct, consistent with their distinctive molecular profiles presumably resulting from different etiological pathways. Functional analyses should lead to further insights into the biological basis of the different glioma histologies. Such information can inform gene discovery initiatives and therefore have a measurable impact on the successful development of new therapeutic agents.

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Dataset Information

Image Analysis Reveals Microstructural and Volumetric Differences in Glioblastoma Patients with and without Preoperative Seizures.

Publications

Image Analysis Reveals Microstructural and Volumetric Differences in Glioblastoma Patients with and without Preoperative Seizures.

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