nach oben

Erschienen in:

17.04.2018 | Clinical Study

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

verfasst von: Johann-Martin Hempel, Cornelia Brendle, Benjamin Bender, Georg Bier, Marco Skardelly, Irina Gepfner-Tuma, Franziska Eckert, Ulrike Ernemann, Jens Schittenhelm

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

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 IDH_wild-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 IDH_wild-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 IDH_wild-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.

Nur mit Berechtigung zugänglich

Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1 CrossRefPubMed

Scott JN, Brasher PMA, Sevick RJ et al (2002) How often are nonenhancing supratentorial gliomas malignant? A population study. Neurology 59(6):947–949CrossRefPubMed

Watanabe M, Tanaka R, Takeda N (1992) Magnetic resonance imaging and histopathology of cerebral gliomas. Neuroradiology 34(6):463–469CrossRefPubMed

Reuss DE, Kratz A, Sahm F et al (2015) Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities. Acta Neuropathol 130(3):407–417. https://doi.org/10.1007/s00401-015-1454-8 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

Sahm F, Reuss D, Koelsche C et al (2014) Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma. Acta Neuropathol 128(4):551–559. https://doi.org/10.1007/s00401-014-1326-7 CrossRefPubMed

Ebrahimi A, Skardelly M, Bonzheim I et al (2016) ATRX immunostaining predicts IDH and H3F3A status in gliomas. Acta Neuropathol Commun 4(1):60. https://doi.org/10.1186/s40478-016-0331-6 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

10.

Hegi ME, Diserens A-C, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003. https://doi.org/10.1056/NEJMoa043331 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

12.

Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. https://doi.org/10.1056/NEJMoa043330 CrossRefPubMed

13.

Gutman DA, Cooper LAD, Hwang SN et al (2013) MR imaging predictors of molecular profile and survival: multi-institutional study of the TCGA glioblastoma data set. Radiology 267(2):560–569. https://doi.org/10.1148/radiol.13120118 CrossRefPubMedPubMedCentral

14.

Hammoud MA, Sawaya R, Shi W et al (1996) Prognostic significance of preoperative MRI scans in glioblastoma multiforme. J Neurooncol 27(1):65–73CrossRefPubMed

15.

Chaichana KL, Kosztowski T, Niranjan A et al (2010) Prognostic significance of contrast-enhancing anaplastic astrocytomas in adults. J Neurosurg 113(2):286–292. https://doi.org/10.3171/2010.2.JNS091010 CrossRefPubMed

16.

Lacroix M, Abi-Said D, Fourney DR et al (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95(2):190–198. https://doi.org/10.3171/jns.2001.95.2.0190 CrossRefPubMed

17.

Perez-Beteta J, Martinez-Gonzalez A, Molina D et al (2017) Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study. Eur Radiol 27(3):1096–1104. https://doi.org/10.1007/s00330-016-4453-9 CrossRefPubMed

18.

Garzon B, Emblem KE, Mouridsen K et al (2011) Multiparametric analysis of magnetic resonance images for glioma grading and patient survival time prediction. Acta Radiol 52(9):1052–1060. https://doi.org/10.1258/ar.2011.100510 CrossRefPubMed

19.

Pope WB, Sayre J, Perlina A et al (2005) MR imaging correlates of survival in patients with high-grade gliomas. AJNR Am J Neuroradiol 26(10):2466–2474PubMed

20.

Pope WB, Chen JH, Dong J et al (2008) Relationship between gene expression and enhancement in glioblastoma multiforme: exploratory DNA microarray analysis. Radiology 249(1):268–277. https://doi.org/10.1148/radiol.2491072000 CrossRefPubMedPubMedCentral

21.

Wang YY, Wang K, Li SW et al (2015) Patterns of tumor contrast enhancement predict the prognosis of anaplastic gliomas with IDH1 mutation. AJNR Am J Neuroradiol 36(11):2023–2029. https://doi.org/10.3174/ajnr.A4407 CrossRefPubMed

22.

Reyes-Botero G, Dehais C, Idbaih A et al (2014) Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression. Neuro-oncology 16(5):662–670. https://doi.org/10.1093/neuonc/not235 CrossRefPubMed

23.

Sonoda Y, Shibahara I, Kawaguchi T et al (2015) Association between molecular alterations and tumor location and MRI characteristics in anaplastic gliomas. Brain Tumor Pathology 32(2):99–104. https://doi.org/10.1007/s10014-014-0211-3 CrossRefPubMed

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 CrossRefPubMed

25.

Elm E von, Altman DG, Egger M et al (2008) The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61(4):344–349. https://doi.org/10.1016/j.jclinepi.2007.11.008 CrossRef

26.

Capper D, Weissert S, Balss J et al (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20(1):245–254. https://doi.org/10.1111/j.1750-3639.2009.00352.x CrossRefPubMed

27.

Hartmann C, Meyer J, Balss J et al (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118(4):469–474. https://doi.org/10.1007/s00401-009-0561-9 CrossRefPubMed

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 CrossRefPubMed

29.

Gerson SL (2004) MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 4(4):296–307. https://doi.org/10.1038/nrc1319 CrossRefPubMed

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 CrossRefPubMed

31.

Suzuki H, Aoki K, Chiba K et al (2015) Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 47(5):458–468. https://doi.org/10.1038/ng.3273 CrossRefPubMed

32.

Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174CrossRefPubMed

33.

Tarone RE, Ware J (1977) On distribution-free tests for equality of survival distributions. Biometrika 64(1):156–160. https://doi.org/10.1093/biomet/64.1.156 CrossRef

34.

Bouliotis G, Billingham L (2011) Crossing survival curves: alternatives to the log-rank test. Trials 12(Suppl 1): A137. https://doi.org/10.1186/1745-6215-12-S1-A137 CrossRefPubMedCentral

35.

Pierallini A, Bonamini M, Bozzao A et al (1997) Supratentorial diffuse astrocytic tumours: proposal of an MRI classification. Eur Radiol 7(3):395–399. https://doi.org/10.1007/s003300050173 CrossRefPubMed

36.

Qi S, Yu L, Li H et al (2014) Isocitrate dehydrogenase mutation is associated with tumor location and magnetic resonance imaging characteristics in astrocytic neoplasms. Oncol Lett 7(6):1895–1902. https://doi.org/10.3892/ol.2014.2013 CrossRefPubMedPubMedCentral

37.

Leu K, Ott GA, Lai A et al (2017) Perfusion and diffusion MRI signatures in histologic and genetic subtypes of WHO grade II-III diffuse gliomas. J Neurooncol. https://doi.org/10.1007/s11060-017-2506-9 PubMedCrossRef

38.

Wiestler B, Capper D, Holland-Letz T et al (2013) ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol 126(3):443–451. https://doi.org/10.1007/s00401-013-1156-z CrossRefPubMed

39.

Olar A, Wani KM, Alfaro-Munoz KD et al (2015) IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol 129(4):585–596. https://doi.org/10.1007/s00401-015-1398-z CrossRefPubMedPubMedCentral

40.

Upadhyay N, Waldman AD (2011) Conventional MRI evaluation of gliomas. Br J Radiol 84(2):S107–S111. https://doi.org/10.1259/bjr/65711810 CrossRef

41.

Unruh D, Schwarze SR, Khoury L et al (2016) Mutant IDH1 and thrombosis in gliomas. Acta Neuropathol 132(6):917–930. https://doi.org/10.1007/s00401-016-1620-7 CrossRefPubMedPubMedCentral

Titel: Contrast enhancement predicting survival in integrated molecular subtypes of diffuse glioma: an observational cohort study
verfasst von: Johann-Martin Hempel
Cornelia Brendle
Benjamin Bender
Georg Bier
Marco Skardelly
Irina Gepfner-Tuma
Franziska Eckert
Ulrike Ernemann
Jens Schittenhelm
Publikationsdatum: 17.04.2018
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 2/2018
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-2872-y

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Introduction

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery

Machine learning: a useful radiological adjunct in determination of a newly diagnosed glioma’s grade and IDH status

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide

Investigation of the aryl hydrocarbon receptor and the intrinsic tumoral component of the kynurenine pathway of tryptophan metabolism in primary brain tumors

Treatment and survival of glioblastoma patients in Denmark: The Danish Neuro-Oncology Registry 2009–2014