Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas

Abstract

<jats:p>The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs are important to consider. Current strategies that make use of molecular markers and imaging techniques and therapeutic considerations offer additional options for management of LGGs. Mutations in the isocitrate dehydrogenase 1 and 2 (<jats:italic>IDH1</jats:italic> and <jats:italic>IDH2</jats:italic>) genes suggest a role for this abnormal metabolic pathway in the pathogenesis and progression of these primary brain tumors. Use of magnetic resonance spectroscopy can provide preoperative detection of <jats:italic>IDH</jats:italic>-mutated gliomas and affect surgical planning. In addition, <jats:italic>IDH1</jats:italic> and <jats:italic>IDH2</jats:italic> mutation status may have an effect on surgical resectability of gliomas. The <jats:italic>IDH</jats:italic>-mutated tumors exhibit better prognosis throughout every grade of glioma, and mutation may be an early genetic event, preceding lineage-specific secondary and tertiary alterations that transform LGGs into secondary glioblastomas. The O6-methylguanine-DNAmethyltransferase <jats:italic>(MGMT)</jats:italic> promoter methylation and <jats:italic>1p19q</jats:italic> codeletion status can predict sensitivity to chemotherapy and radiation in low- and intermediate-grade gliomas. Thus, these recent advances, which have led to a better understanding of how molecular, genetic, and epigenetic alterations influence the pathogenicity of the different histological grades of gliomas, can lead to better prognostication and may lead to specific targeted surgical interventions and medical therapies.</jats:p>

Local image variance of 7 Tesla SWI is a new technique for preoperative characterization of diffusely infiltrating gliomas: correlation with tumour grade and IDH1 mutational status

“…The preoperative knowledge of the IDH1 status is of major interest for further patient management/surgical strategy since it was shown in a recent study that the IDH1 mutational status has a crucial impact on the surgical benefit: While patients with IDH1 wild-type malignant gliomas do not profit from further removal of the non-enhancing tumour in addition to the enhancing tumour, this surgical strategy results in a significantly prolonged overall survival in patients with IDH1 mutant tumours [12, 13]. Interestingly, we observed a significantly higher mean SWI-LIV in IDH1-R132H negative compared to IDH1-R132H positive gliomas.…”

“…More and more, molecular markers such as the IDH1 mutational status are increasingly incorporated in clinical decision making in addition to the tumour grade. Furthermore, it has been recently demonstrated that IDH1 mutant gliomas particularly profit from aggressive tumour resections [12, 13]. Similarly to different microvascular patterns in gliomas of various grades of malignancy, neo-angiogenesis, and thus formation of pathological microvessels was found to be associated with IDH1/2 mutational status with increased neo-angiogenesis in IDH1/2 wild-type gliomas and inhibition of neo-angiogenesis in IDH1/2 mutant tumours [14].…”

Re-irradiation for Recurrent Primary Brain Tumors

“…The generally small study size is dangerous as inclusion of patients with a more favorable tumor biology in some studies could result in better survival and erroneous conclusions about treatment efficacy when comparing different subgroups. The impact of certain biological features has only been realized in recent years (96)(97)(98). In addition, some studies included patients with histological grade change, e.g.…”

Oligoastrocytoma: A Vanishing Tumor Entity

“…Studies have shown that the standard of care for 1p/19q co-deleted oligodendroglial tumors should be the combination of CHT and radiotherapy (RT). In OA, a favourable prognosis was associated to young age, grade II and extent of resection [26].…”