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Multicenter Study
. 2020 Apr 15;22(4):515-523.
doi: 10.1093/neuonc/noz200.

Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria

C Mircea S Tesileanu  1 , Linda Dirven  2   3 , Maarten M J Wijnenga  1 , Johan A F Koekkoek  2   3 , Arnaud J P E Vincent  4 , Hendrikus J Dubbink  5 , Peggy N Atmodimedjo  5 , Johan M Kros  5 , Sjoerd G van Duinen  6 , Marion Smits  7 , Martin J B Taphoorn  2   3 , Pim J French  1 , Martin J van den Bent  1
Affiliations
Multicenter Study

Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria

C Mircea S Tesileanu et al. Neuro Oncol. .

Abstract

Background: The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) has recommended that isocitrate dehydrogenase 1 and 2 wildtype (IDH1/2wt) diffuse lower-grade gliomas (LGGs) World Health Organization (WHO) grade II or III that present with (i) a telomerase reverse transcriptase promoter mutation (pTERTmt), and/or (ii) gain of chromosome 7 combined with loss of chromosome 10, and/or (iii) epidermal growth factor receptor (EGFR) amplification should be reclassified as diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV (IDH1/2wt astrocytomas WHO IV). This paper describes the overall survival (OS) of IDH1/2wt astrocytoma WHO IV patients, and more in detail patients with tumors with pTERTmt only.

Methods: In this retrospective multicenter study, we compared the OS of 71 IDH1/2wt astrocytomas WHO IV patients, with radiological characteristics of LGGs, with the OS of 197 IDH1/2wt glioblastoma patients. Moreover, we compared the OS of 22 pTERTmt only astrocytoma patients with the OS of the IDH1/2wt glioblastoma patients.

Results: Median OS was similar for IDH1/2wt astrocytoma WHO IV patients (23.8 mo) and IDH1/2wt glioblastoma patients (19.2 mo) (Cox proportional hazards model: hazard ratio [HR] 1.27, 95% CI: 0.85-1.88, P = 0.242). OS was also similar in patients with IDH1/2wt astrocytomas WHO IV, pTERTmt only, and IDH1/2wt glioblastomas (HR 1.15, 95% CI: 0.64-2.10, P = 0.641).

Conclusions: The presented data confirm the cIMPACT-NOW recommendation and we propose that IDH1/2wt astrocytomas WHO IV in the absence of other qualifying mutations should be classified as IDH1/2wt glioblastomas.

Keywords: IDH; TERT; astrocytoma; cIMPACT-NOW; glioblastoma.

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Figures

Fig. 1
Fig. 1
MRIs made at the time of histological diagnosis of 3 different IDH1/2wt LGG patients. (A) Ring-like contrast enhancement on cT1w imaging, suggestive of glioblastoma; the patient was excluded from further analysis. (B) Minor contrast enhancement on cT1w imaging, not suggestive of glioblastoma; the patient was included for further analysis. (C) Typical gliomatosis cerebri on FLAIR imaging; a confluent hyperintense abnormality in at least 3 separate brain lobes.
Fig. 2
Fig. 2
A Venn diagram of the number of patients with TERT promoter mutations, EGFR amplification, and the signature of 7+/10− within our cohort of IDH1/2wt LGGs.
Fig. 3
Fig. 3
A waterfall plot of the mutations as picked up by the glioma-specific NGS panel within the IDH1/2wt LGGs.
Fig. 4
Fig. 4
Kaplan–Meier curves of the OS of the IDH1/2wt astrocytomas WHO II and III, the IDH1/2wt astrocytomas WHO IV, and the IDH1/2wt glioblastomas. The dashed line represents the median OS.
See this image and copyright information in PMC

Comment in

References

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