Contrast enhancement predicting survival in integrated molecular subtypes of diffuse glioma: an observational cohort study
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.
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.
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).
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.
KeywordsGlioma Gadolinium enhancement Contrast enhancement Survival Prognosis
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).
- 5.Reuss DE, Mamatjan Y, Schrimpf D et al (2015) IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. Acta Neuropathol 129(6):867–873. https://doi.org/10.1007/s00401-015-1438-8 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Pekmezci M, Rice T, Molinaro AM et al (2017) Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT // Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT. Acta Neuropathol 133(6):1001–1016. https://doi.org/10.1007/s00401-017-1690-1 CrossRefPubMedGoogle Scholar
- 9.Abedalthagafi M, Phillips JJ, Kim GE et al (2013) The alternative lengthening of telomere phenotype is significantly associated with loss of ATRX expression in high-grade pediatric and adult astrocytomas: a multi-institutional study of 214 astrocytomas. Mod Pathol 26(11):1425–1432. https://doi.org/10.1038/modpathol.2013.90 CrossRefPubMedGoogle Scholar
- 11.van den Bent MJ, Baumert B, Erridge SC et al (2017) Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet 390(10103):1645–1653. https://doi.org/10.1016/S0140-6736(17)31442-3 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Xiong J, Tan W, Wen J et al (2016) Combination of diffusion tensor imaging and conventional MRI correlates with isocitrate dehydrogenase ½ mutations but not 1p/19q genotyping in oligodendroglial tumours. Eur Radiol 26(6):1705–1715. https://doi.org/10.1007/s00330-015-4025-4 CrossRefPubMedGoogle Scholar
- 28.Thon N, Eigenbrod S, Grasbon-Frodl EM et al (2009) Novel molecular stereotactic biopsy procedures reveal intratumoral homogeneity of loss of heterozygosity of 1p/19q and TP53 mutations in World Health Organization grade II gliomas. J Neuropathol Exp Neurol 68(11):1219–1228. https://doi.org/10.1097/NEN.0b013e3181bee1f1 CrossRefPubMedGoogle Scholar
- 30.Reuss DE, Sahm F, Schrimpf D et al (2015) ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 129(1):133–146. https://doi.org/10.1007/s00401-014-1370-3 CrossRefPubMedGoogle Scholar