Contrast enhancement predicting survival in integrated molecular subtypes of diffuse glioma: an observational cohort study

  • Johann-Martin Hempel
  • Cornelia Brendle
  • Benjamin Bender
  • Georg Bier
  • Marco Skardelly
  • Irina Gepfner-Tuma
  • Franziska Eckert
  • Ulrike Ernemann
  • Jens Schittenhelm
Clinical Study

Abstract

Introduction

To assess the predictive value of magnetic resonance imaging (MRI) gadolinium enhancement as a prognostic factor in the 2016 World Health Organization Classification of Tumors of the Central Nervous System integrated glioma groups.

Methods

Four-hundred fifty patients with histopathologically confirmed glioma were retrospectively assessed between 07/1997 and 06/2014 using gadolinium enhancement, survival, and relevant prognostic molecular data [isocitrate dehydrogenase (IDH); alpha-thalassemia/mental retardation syndrome X-linked (ATRX); chromosome 1p/19q loss of heterozygosity; and O6-methylguanine DNA methyltransferase (MGMT)]. The Kaplan–Meier method was used to assess univariate survival data. A multivariate Cox proportional hazards model was performed on significant results from the univariate analysis.

Results

There were significant differences in survival between patient age (p < 0.0001), WHO glioma grades (p < 0.0001), and integrated molecular profiles (p < 0.0001). Patients with IDH1/2 mutation, loss of ATRX expression, and methylated MGMT promoter showed significantly better survival than those with the IDHwild-type (p < 0.0001), retained ATRX expression (p < 0.0001), and unmethylated MGMT promoter (p = 0.019). Survival was significantly better in patients without gadolinium enhancement (p = 0.009) who were in the IDHwild-type glioma and glioma with retained ATRX expression groups (p = 0.018 and 0.030, respectively).

Conclusions

In univariate analysis, the presence of gadolinium enhancement on preoperative MRI scans is an unfavorable factor for survival. Regarding the molecular subgroups, gadolinium enhancement is an unfavorable prognostic factor in gliomas with IDHwild-type and those with ATRX retention. However, in multivariate analysis only patient age, IDH1/2 mutation status, MGMT promoter methylation status, and WHO grade IV are relevant for predicting survival.

Keywords

Glioma Gadolinium enhancement Contrast enhancement Survival Prognosis 

Notes

Acknowledgements

We thank Mrs. Aline Naumann from the Institute of Clinical Epidemiology and Applied Biometry of the Eberhard Karls University of Tübingen for her support in statistics. JS was supported by the Else-Übelmesser Foundation (Grant No. 30.19845).

Supplementary material

11060_2018_2872_MOESM1_ESM.pdf (125 kb)
Supplementary material 1. Supplementary Fig. 1 Survival data among treatment-naïve glioma subgroups. Kaplan–Meier plots illustrating overall patient survival among different age groups (a), WHO grades (b), integrated molecular profiles (c), IDH1/2 mutation status (d), ATRX expression status (e), and MGMT methylation profiles (f). WHO world health organization, IDH1/2 isocitrate dehydrogenase 1/2, ATRX alpha-thalassemia/mental retardation syndrome X-linked, MGMT O6-methylguanine DNA methyltransferase (PDF 125 KB)
11060_2018_2872_MOESM2_ESM.pdf (112 kb)
Supplementary material 2. Supplementary Fig. 2 Survival data for gadolinium enhancement among treatment-naïve glioma subgroups. Kaplan-Meier plots illustrating overall patient survival between present and absent gadolinium enhancement (a) among the integrated glioma groups of IDHmut AS (b), OD1p/19q-LOH (c), and IDHwt GBM (d) in addition to gliomas with IDH1/2 mutation (e), the wild type of IDH (f), ATRX loss of expression (g), and retained ATRX expression (h). IDH1/2 isocitrate dehydrogenase 1/2, IDHmut IDH-mutant, IDHwt IDH wild-type, OD1p/19q-LOH oligodendroglioma with chromosome 1p/19q loss of heterozygosity, ATRX alpha-thalassemia/mental retardation syndrome X-linked (PDF 112 KB)
11060_2018_2872_MOESM3_ESM.docx (15 kb)
Supplementary material 3 (DOCX 14 KB)
11060_2018_2872_MOESM4_ESM.docx (15 kb)
Supplementary material 4 (DOCX 14 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Johann-Martin Hempel
    • 1
    • 6
  • Cornelia Brendle
    • 1
    • 6
  • Benjamin Bender
    • 1
    • 6
  • Georg Bier
    • 1
    • 6
  • Marco Skardelly
    • 2
    • 3
    • 6
  • Irina Gepfner-Tuma
    • 3
    • 6
  • Franziska Eckert
    • 4
    • 6
  • Ulrike Ernemann
    • 1
    • 6
  • Jens Schittenhelm
    • 5
    • 6
  1. 1.Department of Diagnostic and Interventional Neuroradiology, University Hospital TübingenEberhard Karls UniversityTübingenGermany
  2. 2.Department of Neurosurgery, University Hospital TübingenEberhard Karls UniversityTübingenGermany
  3. 3.Interdisciplinary Division of Neuro-Oncology, Departments of Neurology and Neurosurgery, University Hospital Tübingen, Hertie Institute for Clinical Brain ResearchEberhard Karls UniversityTübingenGermany
  4. 4.Department of Radiation Oncology, University Hospital TübingenEberhard Karls UniversityTübingenGermany
  5. 5.Institute of Neuropathology, Department of Pathology and Neuropathology, University Hospital TübingenEberhard Karls UniversityTübingenGermany
  6. 6.Center for CNS Tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital TübingenEberhard Karls UniversityTübingenGermany

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