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Clin Neurol Neurosurg. 2019 Dec;187:105556. doi: 10.1016/j.clineuro.2019.105556. Epub 2019 Oct 12.

Relevance of calcification and contrast enhancement pattern for molecular diagnosis and survival prediction of gliomas based on the 2016 World Health Organization Classification.

Author information

1
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: wayside.bamboo@gmail.com.
2
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: hatanobu@ns.med.kyushu-u.ac.jp.
3
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: mmizoguc@ns.med.kyushu-u.ac.jp.
4
Department of Molecular Imaging & Diagnosis, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: hiwatasi@radiol.med.kyushu-u.ac.jp.
5
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: kuga@ns.med.kyushu-u.ac.jp.
6
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: ryhatae@ns.med.kyushu-u.ac.jp.
7
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: yakagi@med.kyushu-u.ac.jp.
8
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: takeo.amay.0330@gmail.com.
9
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: yutakafujioka19830816@yahoo.co.jp.
10
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: togao@radiol.med.kyushu-u.ac.jp.
11
Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: sosuzuki@np.med.kyushu-u.ac.jp.
12
Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University 8-35-1 Sakuragaoka, Kagoshima 890-0075, Japan. Electronic address: kyoshimo@m.kufm.kagoshima-u.ac.jp.
13
Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: iwaki@np.med.kyushu-u.ac.jp.
14
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: kiihara@ns.med.kyushu-u.ac.jp.

Abstract

OBJECTIVES:

The significance of conventional neuroimaging features for predicting molecular diagnosis and patient survival based on the updated World Health Organization (WHO) classification remains uncertain. We assessed the relevance of neuroimaging features (ring enhancement [RE], non-ring enhancement [non-RE], overall gadolinium enhancement [GdE], and intratumoral calcification [IC]) for molecular diagnosis and survival in glioma patients.

PATIENTS AND METHODS:

We evaluated 234 glioma patients according to the updated WHO classification. Isocitrate dehydrogenase (IDH), H3F3A, BRAF hotspot mutations, TERT promotor mutation, and chromosome 1p/19q co-deletion were examined. RE, non-RE, GdE, and IC were evaluated as significant neuroimaging findings. Kaplan-Meier analyses were performed to evaluate overall survival (OS) and the correlations of prognostic factors were evaluated by log-rank tests. Univariate and multivariate analyses were performed to detect prognostic factors for OS.

RESULTS:

A total of 207 patients were eligible. In 110 patients presenting RE, 102 (93%) were glioblastoma (GBM), IDH-wild type. In 97 patients without RE, presence of GdE or IC were not significantly different between IDH-mutant and -wild type tumors, whereas presence of GdE was a significant indicator of higher WHO grades. IC was the only significant finding for 1p/19q co-deleted tumors. TERT promoter mutation was observed in 7/17 patients with diffuse astrocytic glioma, IDH-wild type; recently-defined as "molecular GBM." IC, RE, and GdE were observed with lower prevalence in molecular GBMs. While presence of RE, GdE, and absence of IC were significant factors of OS in overall cohort, presence of GdE was not significant in OS in cases without RE, and IDH-mutant tumors. IC was a significant predictor of favorable OS in cases without RE and IDH-wild type tumors. Multivariate analysis also validated these findings.

CONCLUSION:

GdE alone is not a significant predictor of IDH mutation status, but the pattern of enhancement is a significant predictor with RE demonstrating high sensitivity and specificity for GBM, IDH-wild type. Predicting "molecular GBM" by conventional neuroimaging is difficult. Moreover, GdE is not a significant factor of survival analyzed with pattern of enhancement or molecular stratifications. IC is an important radiographic finding for predicting molecular diagnosis and survival in glioma patients.

KEYWORDS:

Calcification; Enhancement; Glioma; Molecular diagnosis; Survival; World Health Organization Classification

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