EBRO 2017

Case 3 pathology notes

• Recent work suggest an integrated pathology approach may help

• The TCGA paper looks at 293 pts with grade 2/3 gliomas. They suggest that LGG with IDH-wild type are essentially GBMs (Fig. 4, Fig. 5B), and are distinct from other LGG, in that they occur in older patients, and in different locations. For these patients, survival is intermediate between 'true' GBM with IDH-wt and GBM with mutated IDH-mutation.

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• It is work remembering that those with IDH-mut and 1p/19q still only had a median OS of 8 years, which is better - but still worse than many cancers. IDH-wt GBM is still the worst disease - which suggests that grade still plays some role in prognosis.

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• The Eckel-Passow paper looks at IDH, 1p/19q and TERT promoter mutations. Genetics was associated with survival in Grade 2/3 gliomas, but not in GBM. Tumours with TERT mutations only did really very badly, even if they were grade 2/3 (although most TERT-mut only tumours were GBM).

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• There are still some significant outstanding issues: data on performance status and treatment is incomplete (and one might think has some impact on outcome), and although the molecular groups segregate well, they are not perfect (e.g. the inverse association by TERT and ATRX - but not in everyone; the idea that IDH-mut is not prognostic in GBM patients with TERT mutations). Some of these are also subject to small-cohort problems.

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• Nonetheless, I think the data are interesting, but mainly for grade 2/3 tumours (GBMs do badly, and grade still matters). This might end up pushing us towards more tissue sampling in those with lower-grade tumours, in order to risk stratify. The impact on treatment is less clear, although one can make an argument that in someone with a grade II TERT-mut astrocytoma, the outcomes are so poor one should treat them as a GBM. I am not convinced we have the evidence for this yet - the fact they do badly doesn't mean that they do better with CRT.

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• As ever, I am happy to discuss - although I am not a molecular pathologist!

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