Molecular glioblastomas – the same but different?

The 2021 WHO-classification changed the classification of gliomas from solely histopathological criteria to molecular genetic characteristics. IDH-wildtype (wt) diffuse astrocytomas (LGG) which prior to the 2021 classification were classified as grade II, are now diagnosed as IDH-wt gliomas with molecular characteristics of glioblastomas (mGBM) when harbouring certain molecular abnormalities like chromosomal +7/-10 copy alterations, TERT promotor mutation, EGFR amplification and CDKN2A/B deletion. mGBM grade 4 are widely treated as the earlier WHO grade IV GBM with patients undergoing adjuvant radiochemotherapy. Whether early cytotoxic treatment truly improve patient"s outcome and is favourable in every case is not clear at present.

We retrospectively analysed overall survival (OS) and tumor characteristics as well as adjuvant treatment of a total of 46 histopathological grade 2 IDH-wt LGG treated between 2012 and 2021 prior to the introduction of the 2021 WHO classification, and identified those with molecular characteristics of glioblastomas. We than searched for influencing factors on decision making for adjuvant treatment or watch-and-wait strategies using multivariant analysis. The comparison of OS between the 4 groups was performed using Kaplan-Meier estimators.

In our cohort we found that extent of resection (EOR, p<0.001) and age (p=0.033) significantly and independently influenced the decision for adjuvant therapies (p<0.05). Contrast enhancement on MRI was marginally significant (p=0.086), whereas molecularpathological diagnosis and the patient`s level of functioning (ECOG performance status) did not significantly affect this decision. When comparing OS, we found no observable difference between mGBM and IDH-wt LGG without adjuvant therapy as well as between these two entities treated with early adjuvant cytotoxic therapy. Overall, we observed a difference in OS between patients with adjuvant therapy and those without.

EOR and age drove the decision for adjuvant therapy in presumed IDH wt LGG prior to the 2021 classification of brain tumors, rather than the distinction of molecular GBM. In our cohort patients with mGBM without adjuvant therapy did not do worse than other patients with histopathological IDH-wt LGG. These observation question whether adjuvant therapy should be performed in mGBM with good resection status, lack of enhancement, and younger age, with respect to possible side effects.