Prognostic and predictive impact of MGMT promoter methylation status in high risk grade II glioma...
The importance of the molecular signature of low grade gliomas has risen highly over the last years. The occurrence of IDH mutation, TERT mutation, CDKN2A mutation and hystona alteration have been discussed. Differently from high grade gliomas, the MGMT methylation status (mMGMT) has not yet been established as a prognostic and predictive marker.
Haque et al (2022) did a retrospective analysis with data from an oncology database of the US. For treatment purposes, patients are traditionally subdivided into high or low risk. Risk assessment goes mainly through age (>40 year-old) and extent of resection (subtotal resection). Of the 11,223 grade II gliomas from this study, 9,971 (89%) had no mMGMT testing. Of the following patients, 634 (50.6%) were mMGMT and 618 (49.4%) were uMGMT. The mMGMT group presented with greater overall survival (OS) when compared to the uMGMT (77.3m x 42.6m). Untested group presented with intermediate results (61.9m).
In the subgroup analysis, MGMT status was predictive of greater OS in the gross total resection x subtotal and biopsy groups (p<0.001). OS was also greater in oligodendrogliomas and oligoastro histology versus astrocytomas. When analyzing adjuvant treatment, patients were divided into submitted to chemoradiation vs isolated chemotherapy vs isolated radiotherapy vs no adjuvant treatment. mMGMT status predicted a greater OS in the chemoradiation and the isolated radiotherapy groups only. Authors discuss the lack of OS difference in the isolated chemotherapy group as possibly due to the small sample of this subgroup, a possible mechanism of resistance undetected, and possibly different types of chemo used (there was no data available as to which drugs were used).
Despite its limitations (retrospective study, based on database data which may be incomplete), this study raises the question if we should start giving more value to mMGMT status as a prognostic factor also in the low grade glioma population.
Larissa Vilany is a Neurological surgeon from University of Campinas
Current Neuro-oncology fellow from SNOLA
Article link: DOI: 10.1007/s11060-022-03955-3