Dataset Information

Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings.

ABSTRACT:

Background

Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS).

Methods

Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis (N_LTS = 23) or <3 years (N_STS = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) (N_LTS = 23; N_STS = 74) and methylation analysis (N_LTS = 18; N_STS = 28). Pre-surgical MRI scans for a subset of LTS (N = 14) and STS control (N = 28) matched on sex, age, and extent of resection were analyzed.

Results

LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMTp methylation and tumor protein 53 (TP53) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers.

Conclusions

Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis.

SUBMITTER: Briceno N

PROVIDER: S-EPMC10901543 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings.

Briceno Nicole N Vera Elizabeth E Komlodi-Pasztor Edina E Abdullaev Zied Z Choi Anna A Grajkowska Ewa E Kunst Tricia T Levine Jason J Lindsley Matthew M Fernandez Kelly K Reyes Jennifer J Boris Lisa L Burton Eric E Panzer Marissa M Polskin Lily L Penas-Prado Marta M Pillai Tina T Theeler Brett J BJ Wu Jing J Wall Kathleen K Papanicolau-Sengos Antonios A Quezado Martha M Smirniotopoulos James J Aldape Kenneth K Armstrong Terri S TS Gilbert Mark R MR

Neuro-oncology advances 20240101 1

<h4>Background</h4>Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS).<h4>Methods</h4>Molecularly confirmed Isocitrat ...[more]

PMID: 38420614

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Project description:Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTS) may provide important insight into the biology of GBM. We identified 7 patients with GBM treated at Memorial Sloan-Kettering Cancer Center (MSKCC) with survival greater than 48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTS in two independent cohorts (TCGA and REMBRANDT) and analyzed the transcriptomal characteristics of these LTS. The median overall survival of our cohort was 62.5 months. LTS were distributed between the proneural (n=2), neural (n=2), classical (n=2) and mesenchymal (n=1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identity. The majority of the MSKCC LTS (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutations, and IDH mutation occurred in a minority of the TCGA LTS as well. A set of 42 genes was found to be differentially expressed in the MSKCC and TCGA LTS. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression. All tumors (n = 7) were obtained following surgical resection at the MSKCC as part of routine clinical care, and snap frozen. Tumors were obtained in accordance with Institutional Review Board policies at the MSKCC. Each sample was examined histologically by 3 independent neuropathologists and confirmed to be World Health Organization (WHO) grade IV glioma (GBM). Before analysis, tumors were sectioned and microdissected. Genomic DNA or RNA was extracted using the DNeasy kit (Qiagen) or RNeasy Lipid Tissue Mini Kit (Qiagen) as per the manufacturer’s instructions. Expression analysis of tumors was performed using the Affymetrics U133 2.0 microarray (Affymetrix). Affymetrix CEL files were imported into the Partek Genomics Suite (Partek). The TCGA gene expression data (HT-HG-U133A) was accessed from the TCGA data repositories (http://cancergenome.nih.gov, date of download 12/2013).

Dataset Information

Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings.

Background

Methods

Results

Conclusions

Publications

Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings.

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