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

Nicole Briceno, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Elizabeth Vera, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Edina Komlodi-Pasztor, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Zied Abdullaev, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Anna Choi, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Ewa Grajkowska, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Tricia Kunst, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Jason Levine, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Matthew Lindsley, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Kelly Fernandez, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Jennifer Reyes, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Lisa Boris, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
Eric Burton, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Marissa Panzer, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Lily Polskin, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Marta Penas-Prado, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Tina Pillai, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Brett J. Theeler, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Jing Wu, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Kathleen Wall, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Antonios Papanicolau-Sengos, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Martha Quezado, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
James Smirniotopoulos, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Kenneth Aldape, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Terri S. Armstrong, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Mark R. Gilbert, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Document Type

Journal Article

Publication Date

1-1-2024

Journal

Neuro-oncology advances

Volume

6

Issue

1

DOI

10.1093/noajnl/vdae019

Keywords

glioblastoma; long-term survivor; methylation; predictors

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 wildtype GBM patients living ≥3 years post-diagnosis ( = 23) or <3 years ( = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) ( = 23;  = 74) and methylation analysis ( = 18;  = 28). Pre-surgical MRI scans for a subset of LTS ( = 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 p methylation and tumor protein 53 () 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.

Department

Radiology

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