High-Grade Gliomas with Long Survival: How & Why?

Murat BÜYÜKTEPEa , Hasan Çağlar UĞURb

aÜnye State Hospital, Clinic of Neurosurgery, Ordu, Türkiye
bAnkara University Faculty of Medicine, Department of Neurosurgery, Ankara, Türkiye

Büyüktepe M, Uğur HÇ. High-grade gliomas with long survival: How & why? In: Uğur HÇ, Bayatlı E, eds. Glial Tumours: Expectations from Today-Promises of the Future. 1st ed. An- kara: Türkiye Klinikleri; 2024. p.49-57.

ABSTRACT

High grade gliomas are the most common primary malignant brain tumors. Despite the recent ad- vancements in the field of diagnosis and treatment of high grade gliomas, the prognosis of the disease still re- mains poor, with a median survival of less than 2 years. Nevertheless, the presence of some cases with much longer survival than expected has raised many questions regarding the prognostic factors. This article aims to summarize the prognostic factors for high-grade gliomas and question the reasons for long survival of glial tumor patients. Young age, high Karnofsky performance score, supratotal resection of the tumor, grade and histopathological type of the tumor are known predictors for treatment response and overall survival. Progno- sis is better in tumors with supratentorial and cerebellar localization, without extension to eloquent brain areas or spread to the midline. Besides, molecular profiling has begun to play a prominent role in determining prog- nosis of high grade glioma patients. The recently revised classification of high grade gliomas based on molec- ular profiling, notably isocitrate dehydrogenase (IDH) mutation status, is a result of enhanced understanding of the prognostic role of molecular markers. In addition to IDH mutation, O-methyl guanine methyltransferase (MGMT) promoter methylation was found to be related with an increased temozolomide response and thereby increased survival time. The co-occurrence of IDH1 mutation and MGMT promoter methylation was reported to have synergistic effect on patients survivial. Several molecular markers including chromosome 1p/19q co- deletion, cyclin-dependent kinase inhibitor (CDKN) status and telomerase reverse transcriptase (TERT) pro- moter mutations were also discussed in this review. As a conclusion, both the tumor- or patient-related factors have the potential to explain the alterations in patients survival and tumour behavior in high grade gliomas. Still, there is a lot of need to describe new prognostic factors, to develop new therapeutic options through per- sonalized approaches that use molecular profiling and predictive biomarkers, to improve patients survival with high grade gliomas.

Keywords: High grade glioma; glioblastoma; prognosis; survival; biomarkers

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