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Imaging predictors of 4q12 amplified and RB1 mutated glioblastoma IDH-wildtype

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Abstract

Introduction

Recent studies have identified that glioblastoma IDH-wildtype consists of different molecular subgroups with distinct prognoses. In order to accurately describe and classify gliomas, the Visually AcceSAble Rembrandt Images (VASARI) system was developed. The goal of this study was to evaluate the VASARI characteristics in molecular subgroups of IDH-wildtype glioblastoma.

Methods

A retrospective analysis of glioblastoma IDH- wildtype with comprehensive next-generation sequencing and pre-operative and post-operative MRI was performed. VASARI characteristics and 205 genes were evaluated. Multiple comparison adjustment by the Bejamin-Hochberg false discovery rate (BH-FDR) was performed. A 1:3 propensity score match (PSM) with a Caliper of 0.2 was done.

Results

178 patients with GBM IDH-WT met the inclusion criteria. 4q12 amplified patients (n = 20) were associated with cyst presence (30% vs. 12%, p = 0.042), decreased hemorrhage (35% vs. 62%, p = 0.028), and non-restricting/mixed (35%/60%) rather than restricting diffusion pattern (5%), meanwhile, 4q12 non-amplified patients had mostly restricting (47.4%) rather than a non-restricting/mixed diffusion pattern (28.4%/23.4%). This remained statistically significant after BH-FDR adjustment (p = 0.002). PSM by 4q12 amplification showed that diffusion characteristics continued to be significantly different. Among RB1-mutant patients, 96% had well-defined enhancing margins vs. 70.6% of RB1-WT (p = 0.018), however, this was not significant after BH-FDR or PSM.

Conclusions

Patients with glioblastoma IDH-wildtype harboring 4q12 amplification rarely have restricting DWI patterns compared to their wildtype counterparts, in which this DWI pattern is present in ~ 50% of patients. This suggests that some phenotypic imaging characteristics can be identified among molecular subtypes of IDH-wildtype glioblastoma.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding authors upon reasonable request.

Code availability

Not applicable.

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Acknowledgements

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Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number K08CA241651 (LYB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, 77030, Houston, TX, USA

    Antonio Dono, Jose Torres, Nitin Tandon & Yoshua Esquenazi

  2. Department of Diagnostic and Interventional Imaging, McGovern Medical School, The University of Texas Health Science Center at Houston, 77030, Houston, TX, USA

    Luis Nunez, Octavio Arevalo, Roy F. Riascos & Arash Kamali

  3. Department of Radiology, LSU Health Shreveport, 71103, Shreveport, LA, USA

    Octavio Arevalo

  4. Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 77030, Houston, TX, USA

    Juan Carlos Rodriguez-Quinteros

  5. Memorial Hermann Hospital-TMC, 77030, Houston, TX, USA

    Roy F. Riascos, Arash Kamali, Nitin Tandon & Yoshua Esquenazi

  6. Department of Pathology, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA

    Leomar Y. Ballester

  7. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA

    Leomar Y. Ballester

  8. Center for Precision Health, School of Biomedical Informatics, the University of Texas Health Science Center at Houston, 77030, Houston, TX, USA

    Yoshua Esquenazi

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  1. Antonio Dono
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Contributions

Study design: A.D., Y.E. Data collection: A.D., L.N., O.A., J.C.RQ. Data analysis: A.D., J.T., Manuscript draft writing: A.D., J.T., L.N. Manuscript editing: A.D., L.N., O.A., R.F.R., A.K., N.T., L.Y.B., Y.E. Manuscript approval: all authors.

Corresponding author

Correspondence to Yoshua Esquenazi.

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No conflicts of interest were reported by the authors.

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This study was approved by the institutional review board of The University of Texas Health Science Center at Houston and Memorial Hermann Hospital, Houston, TX and it was in accordance with the 1964 Helsinki Declaration and its later amendments.

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The authors declare no competing interests.

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Dono, A., Torres, J., Nunez, L. et al. Imaging predictors of 4q12 amplified and RB1 mutated glioblastoma IDH-wildtype. J Neurooncol 167, 99–109 (2024). https://doi.org/10.1007/s11060-024-04575-9

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