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Multicenter Study
. 2015 Jun;129(6):867-73.
doi: 10.1007/s00401-015-1438-8. Epub 2015 May 12.

IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO

David E Reuss  1 , Yasin Mamatjan, Daniel Schrimpf, David Capper, Volker Hovestadt, Annekathrin Kratz, Felix Sahm, Christian Koelsche, Andrey Korshunov, Adriana Olar, Christian Hartmann, Jaap C Reijneveld, Pieter Wesseling, Andreas Unterberg, Michael Platten, Wolfgang Wick, Christel Herold-Mende, Kenneth Aldape, Andreas von Deimling
Affiliations
Multicenter Study

IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO

David E Reuss et al. Acta Neuropathol. 2015 Jun.

Abstract

The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A II(WHO2007)) and anaplastic astrocytoma WHO grade III (AA III(WHO2007)). Patients with A II(WHO2007) are significantly younger and survive significantly longer than those with AA III(WHO2007). So far, classification and grading relies on morphological grounds only and does not yet take into account IDH status, a molecular marker of prognostic relevance. We here demonstrate that WHO 2007 grading performs poorly in predicting prognosis when applied to astrocytoma carrying IDH mutations. Three independent series including a total of 1360 adult diffuse astrocytic gliomas with IDH mutation containing 683 A II(IDHmut), 562 AA III(IDHmut) and 115 GBM(IDHmut) have been examined for age distribution and survival. In all three series patients with A II(IDHmut )and AA III(IDHmut) were of identical age at presentation of disease (36-37 years) and the difference in survival between grades was much less (10.9 years for A II(IDHmut), 9.3 years for AA III(IDHmut)) than that reported for A II(WHO2007) versus AA III(WHO2007). Our analyses imply that the differences in age and survival between A II(WHO2007) and AA III(WHO2007) predominantly depend on the fraction of IDH-non-mutant astrocytomas in the cohort. This data poses a substantial challenge for the current practice of astrocytoma grading and risk stratification and is likely to have far-reaching consequences on the management of patients with IDH-mutant astrocytoma.

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Figures

Fig. 1
Fig. 1
Box-plots (left panels) and survival statistics (right panels). A II IDHmut in red, AA III IDHmut in blue and GBM IDHmut in black. Three upper pairs depict the IDH-mutant only series from MD Anderson, Heidelberg and TCGA after receiving an integrated diagnosis. The lower pair depicts the TCGA A II WHO2007 and A III WHO2007 without exclusion of IDH wild-type cases. Survival on X-axis in right panels is given in days
Fig. 2
Fig. 2
Age distribution of first tumor diagnosis of A II IDHmut (red) and AA III IDHmut (blue) of 1245 tumors of the combined MD Anderson, TCGA and Heidelberg series. Plots are normalized
Fig. 3
Fig. 3
Age-related survival (in days) in combined group of WHO II and III IDH-mutant from all three series
See this image and copyright information in PMC

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