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The survival outcomes of molecular glioblastoma IDH-wildtype: a multicenter study

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Abstract

Purpose

Histological diagnosis of glioblastoma (GBM) was determined by the presence of necrosis or microvascular proliferation (histGBM). The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM, WHO grade 4) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/− 10 copy changes. The objective of this study was to explore and compare the survival outcomes between histGBM and molGBM.

Methods

Medical records for patients diagnosed with GBM at the three tertiary care academic centers of our institution from November 2017 to October 2021. Only patients who underwent adjuvant chemoradiation were included. Patients without molecular feature testing or with an IDH mutation were excluded. Univariable and multivariable analyses were performed to evaluate progression-free (PFS) and overall- survival (OS).

Results

708 consecutive patients were included; 643 with histGBM and 65 with molGBM. Median PFS was 8 months (histGBM) and 13 months (molGBM) (p = 0.0237) and median OS was 21 months (histGBM) versus 26 months (molGBM) (p = 0.435). Multivariable analysis on the molGBM sub-group showed a worse PFS if there was contrast enhancement on MRI (HR 6.224 [CI 95% 2.187–17.714], p < 0.001) and a superior PFS on patients with MGMT methylation (HR 0.026 [CI 95% 0.065–0.655], p = 0.007).

Conclusions

molGBM has a similar OS but significantly longer PFS when compared to histGBM. The presence of contrast enhancement and MGMT methylation seem to affect the clinical behavior of this subset of tumors.

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Data availability

Data obtained and analyzed in this manuscript is patient confidential. However, non-identified data is available from the corresponding author upon reasonable request.

Abbreviations

+ 7/− 10:

Combined gain of chromosome 7 and loss of chromosome 10

cIMPACT-NOW:

Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy

CI:

Confidence interval

EGFR:

Epidermal growth factor receptor

GBM:

Glioblastoma

HR:

Hazards ratio

histGBM:

Histological glioblastoma

IDH:

Isocitrate dehydrogenase

KPS:

Karnofsky performance score

LV:

Lateral ventricles

MGMT:

O6-Methylguanine-DNA-methyltransferase

molGBM:

Molecular glioblastoma

OS:

Overall survival

PFS:

Progression-free survival

SVZ:

Sub-ventricular zone

TERT:

Telomerase reverse transcriptase

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Funding

AQH was supported by the Mayo Clinic Professorship and a Clinician Investigator award, and Florida State Department of Health Research Grant, and the Mayo Clinic Graduate School, as well as the NIH (R43CA221490, R01CA200399, R01CA195503, and R01CA216855). SHK was supported by the FDA (R01 FD-R-07288). EHM receives unrelated research support from Boston Scientific Corp. and Varian Medical Systems, Inc.

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Authors and Affiliations

  1. Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA

    Andres Ramos-Fresnedo, Michael W. Pullen, Carlos Perez-Vega, Ricardo A. Domingo, Oluwaseun O. Akinduro, Joao P. Almeida, Paola Suarez-Meade, Lina Marenco-Hillembrand, Kaisorn L. Chaichana & Alfredo Quiñones-Hinojosa

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA

    Mark E. Jentoft

  3. Department of Neurosurgery, Mayo Clinic, Phoenix, AZ, USA

    Bernard R. Bendok

  4. Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA

    Daniel M. Trifiletti

  5. Department of Neurology, Mayo Clinic, Phoenix, AZ, USA

    Alyx B. Porter

  6. Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA

    Terence C. Burns

  7. Department of Oncology, Mayo Clinic, Rochester, MN, USA

    Sani H. Kizilbash

  8. Department of Radiology, Mayo Clinic, Jacksonville, FL, USA

    Erik H. Middlebrooks

  9. Division Chair, Neuro-Oncology, Department of Neurology, Mayo Clinic, 4500 San Pablo Rd. S, Jacksonville, FL, 32224, USA

    Wendy J. Sherman

Authors
  1. Andres Ramos-Fresnedo
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  2. Michael W. Pullen
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Contributions

Conceptualization: ARF, MWP, CPV, RAD, OOA, JPA, EHM, WJS. Methodology: ARF, MWP, CPV, RAD, OOA, JPA, DMT, ABP, TCB, SHK, EHM, WJS. Software: ARF, MWP. Validation: ARF, MWP. Formal Analysis: ARF. Investigation: ARF, MWP, CPV, RAD, OOA, JPA. Resources: MEJ, BRB, DMT, KLC, ABP, AQH, TCB, SHK, EHM, WJS. Data Curation: ARF, MWP, CPV, RAD, OOA, JPA, PSM, LM. Writing—Original Draft: ARF, MWP, CPV, RAD, OOA, JPA. Writing—Review and Editing: ARF, MWP, CPV, RAD, OOA, JPA, PSM, LM, MEJ, BRB, DMT, KLC, ABP, AQH, TCB, SHK, EHM, WJS. Visualization: ARF, MWP, CPV, RAD, OOA, JPA, MEJ, BRB, DMT, KLC, ABP, AQH, TCB, SHK, EHM, WJS. Supervision: AQH, EHM, WJS. Project Administration: EHM, WJS. Funding Acquisition: AQH, EHM, WJS.

Corresponding author

Correspondence to Wendy J. Sherman.

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EHM serves on an advisory board and receives consulting fees from Boston Scientific Corp. All other authors have no conflict of interest to disclose.

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Ramos-Fresnedo, A., Pullen, M.W., Perez-Vega, C. et al. The survival outcomes of molecular glioblastoma IDH-wildtype: a multicenter study. J Neurooncol 157, 177–185 (2022). https://doi.org/10.1007/s11060-022-03960-6

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