Dataset Information

Early EEG hyperexcitability is associated with decreased survival in newly diagnosed IDH-wildtype glioma.

ABSTRACT:

Purpose

The relationship between peritumoral neuronal activity, early onset clinical seizures, and glioma survival outcomes remains poorly understood. Hyperexcitability on continuous EEG in the peri-operative period was studied as a prognostic biomarker in patients with newly diagnosed IDH-wildtype diffuse glioma.

Methods

A retrospective observational cohort study was performed including adults with newly diagnosed diffuse glioma, absence of IDH1/2 mutations, and continuous EEG monitoring prior to chemoradiation and within 1 month of initial resection. EEG hyperexcitability was defined by the presence of lateralized periodic discharges and/or electrographic seizures. The primary outcome of overall survival was estimated using the Kaplan-Meier method and compared between groups using multivariate Cox proportional hazards model.

Results

There were 424 patients without continuous EEG and 32 with continuous EEG, of whom lateralized periodic discharges and/or electrographic seizures were seen in 17 (53%). Peri-operative EEG hyperexcitability was associated with decreased overall survival in multivariate analysis (median 12.5 [95% CI 6.2-25.6] months with hyperexcitability versus median 19.9 [95% CI 8.9-53.5] months without hyperexcitability, p = 0.043). Compared to patients without continuous EEG, overall survival was decreased in patients with hyperexcitability (p < 0.0001) and similar in patients without hyperexcitability (p = 0.193). Patients with and without hyperexcitability had similar rates of exposure to anti-seizure medication at baseline, and in long-term follow-up had no difference in number of medications required for seizure control.

Conclusions

These findings indicate the potential prognostic value of a clinical EEG biomarker of glioma aggressiveness prior to the initiation of chemoradiation.

SUBMITTER: Tobochnik S

PROVIDER: S-EPMC9329255 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Early EEG hyperexcitability is associated with decreased survival in newly diagnosed IDH-wildtype glioma.

Tobochnik Steven S Lapinskas Emily E Vogelzang Jayne J Ligon Keith L KL Lee Jong Woo JW

Journal of neuro-oncology 20220617 1

<h4>Purpose</h4>The relationship between peritumoral neuronal activity, early onset clinical seizures, and glioma survival outcomes remains poorly understood. Hyperexcitability on continuous EEG in the peri-operative period was studied as a prognostic biomarker in patients with newly diagnosed IDH-wildtype diffuse glioma.<h4>Methods</h4>A retrospective observational cohort study was performed including adults with newly diagnosed diffuse glioma, absence of IDH1/2 mutations, and continuous EEG mo ...[more]

PMID: 35715666

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Project description:ObjectivesThis study examines clustering based on shape radiomic features and tumor volume to identify IDH-wildtype glioma phenotypes and assess their impact on overall survival (OS).Materials and methodsThis retrospective study included 436 consecutive patients diagnosed with IDH-wt glioma who underwent preoperative MR imaging. Alongside the total tumor volume, nine distinct shape radiomic features were extracted using the PyRadiomics framework. Different imaging phenotypes were identified using partition around medoids (PAM) clustering on the training dataset (348/436). The prognostic efficacy of these phenotypes in predicting OS was evaluated on the test dataset (88/436). External validation was performed using the public UCSF glioma dataset (n = 397). A decision-tree algorithm was employed to determine the relevance of features associated with cluster affiliation.ResultsPAM clustering identified two clusters in the training dataset: Cluster 1 (n = 233) had a higher proportion of patients with higher sphericity and elongation, while Cluster 2 (n = 115) had a higher proportion of patients with higher maximum 3D diameter, surface area, axis lengths, and tumor volume (p < 0.001 for each). OS differed significantly between clusters: Cluster 1 showed a median OS of 23.8 compared to 11.4 months of Cluster 2 in the holdout test dataset (p = 0.002). Multivariate Cox regression showed improved performance with cluster affiliation over clinical data alone (C index 0.67 vs 0.59, p = 0.003). Cluster-based models outperformed the models with tumor volume alone (evidence ratio: 5.16-5.37).ConclusionData-driven clustering reveals imaging phenotypes, highlighting the improved prognostic power of combining shape-radiomics with tumor volume, thereby outperforming predictions based on tumor volume alone in high-grade glioma survival outcomes.Clinical relevance statementShape-radiomics and volume-based cluster analyses of preoperative MRI scans can reveal imaging phenotypes that improve the prediction of OS in patients with IDH-wild type gliomas, outperforming currently known models based on tumor size alone or clinical parameters.Key pointsShape radiomics and tumor volume clustering in IDH-wildtype gliomas are investigated for enhanced prognostic accuracy. Two distinct phenotypic clusters were identified with different median OSs. Integrating shape radiomics and volume-based clustering enhances OS prediction in IDH-wildtype glioma patients.

Project description:BackgroundNF1 inactivation is associated with sensitivity to MEK inhibitor targeted therapy in low-grade and some high-grade gliomas. NF1 loss may also be a harbinger of exploitable vulnerabilities in IDH-wildtype glioblastoma (GBM). Accurate and consistent detection of NF1 loss, however, is fraught given the large gene size, challenges with complete coverage and variant calling upon sequencing, and mechanisms of mRNA and protein regulation that result in early degradation in the absence of genomic alterations. Here, we seek to perform a composite analysis for NF1 loss accounting for genomic alterations and protein expression via immunohistochemistry. We also characterize the landscape of NF1 alterations in GBM.MethodsWe assembled a single-institution, retrospective cohort of 542 IDH-wildtype GBM with somatic next generation sequencing to investigate the frequency and nature of detected NF1 alterations. We selected 69 GBMs from which to build a tissue microarray (TMA) of 44 NF1-wildtype and 25 NF1-mutant cases. We performed NF1 immunohistochemistry using two different NF1 antibodies (NFC, Sigma-Aldrich; and iNF-07E, iNFixion Bioscience) and correlated results with clinical, genomic, and other immunohistochemical features.ResultsIn our retrospective cohort, we identified 88 IDH-wildtype GBM with NF1 alterations (16%). NF1 alterations were mutually exclusive with EGFR and MDM2 alterations (p-adj < 0.001, 0.05, respectively), but co-occurred with PIK3R1 alterations (Log2(OR) = - 1.6, p-adj = 0.03). Of the 63 scorable sporadic GBMs in the TMA, 14 harbored NF1 inactivating alterations and of those, 12 (86%) demonstrated minimal NF1 immunoreactivity by NFC antibody, compared to 8 (57%) by iNF-07E antibody. Among the 42 scorable NF1-wildtype GBM in the TMA, NF1 immunostaining was minimal in 18 (43%) by NFC antibody compared to 4 (10%) by iNF-07E antibody, potentially reflecting false positives or differential protein regulation. Minimal immunoreactivity by NFC antibody was associated with decreased median overall survival (8.5 vs. 16.4 months, p = 0.011). Cox proportional hazards model correcting for prognostic variables in this subset revealed HR 3.23 (95% CI 1.29-8.06, p = 0.01) associated with decreased NF1 expression by IHC.ConclusionNF1 immunostaining may serve as a sensitive surrogate marker of NF1 genomic inactivation and a valuable extension to next-generation sequencing for defining NF1 status. Minimal NF1 immunoreactivity is a poor prognostic marker, even in IDH-wildtype glioblastoma without apparent NF1 genomic alterations, but the underlying molecular mechanism requires further investigation.

Dataset Information

Early EEG hyperexcitability is associated with decreased survival in newly diagnosed IDH-wildtype glioma.

Purpose

Methods

Results

Conclusions

Publications

Early EEG hyperexcitability is associated with decreased survival in newly diagnosed IDH-wildtype glioma.

Similar Datasets

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