Gliomas are the most common central nervous system tumors. New technologies, including genetic research and advanced statistical methods, revolutionize the therapeutic approach to the patient and reveal new points of treatment options. Moreover, the 2021 World Health Organization Classification of Tumors of the Central Nervous System has fundamentally changed the classification of gliomas and incorporated many molecular biomarkers. Given the rapid progress in neuro-oncology, here we compile the latest research on prognostic and predictive biomarkers in gliomas. In adult patients, IDH mutations are positive prognostic markers and have the greatest prognostic significance. However, CDKN2A deletion, in IDH-mutant astrocytomas, is a marker of the highest malignancy grade. Moreover, the presence of TERT promoter mutations, EGFR alterations, or a combination of chromosome 7 gain and 10 loss upgrade IDH-wildtype astrocytoma to glioblastoma. In pediatric patients, H3F3A alterations are the most important markers which predict the worse outcome. MGMT promoter methylation has the greatest clinical significance in predicting responses to temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype predicting poor response to TMZ. Finally, we discussed liquid biopsies, which are promising diagnostic, prognostic, and predictive techniques, but further work is needed to implement these novel technologies in clinical practice.

Glioblastoma is the most malignant central nervous system tumor, which represents 50% of all glial tumors. The understanding of glioma genesis, prognostic evaluation, and treatment planning has been significantly enhanced by the discovery of molecular genetic biomarkers. This study aimed to evaluate survival in patients with primary glioblastoma concerning O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation and other clinical factors. The study included 41 newly diagnosed glioblastoma patients treated from 2011 to 2014 in the 10th Military Research Hospital and Polyclinic, Poland. All patients underwent surgical resection followed by radiation and chemotherapy with alkylating agents. The MGMT promoter methylation was evaluated in all patients, and 43% were found to be methylated. In 26 and 15 cases, gross total resection and subtotal resection were conducted, respectively. Patients with a methylated MGMT promoter had a median survival of 504 days, while those without methylation had a median survival of 329 days. The group that was examined had a median age of 53. In a patient group younger than 53 years, those with methylation had significantly longer overall survival (639 days), compared to 433.5 days for patients without methylation. The most prolonged survival (551 days) was in patients with MGMT promoter methylation after gross total resection. The value of MGMT promoter methylation as a predictive biomarker is widely acknowledged. However, its prognostic significance remains unclear. Our findings proved that MGMT promoter methylation is also an essential positive prognostic biomarker.

Introduction The accurate detection of genetic variants such as single substitutions (IDH1/2, TERT), chromosomal abnormalities (CDKN2A, 1p/19q deletions, and EGFR amplifications), or promoter methylations (MGMT) is critical for glioma patient management, as emphasized in the World Health Organization's (WHO’s) most recent classification in 2021 (WHO CNS5). The purpose of this study was to evaluate novel innovative methods for determining IDH1/2 status in the context of WHO CNS5. Methods Multiple biomarkers were simultaneously screened using next-generation sequencing (NGS) on 34 glioma samples. In cases where the IDH1/2 status determined by immunohistochemistry (IHC) or multiplex ligation-dependent probe amplification (MLPA) was inconsistent with the NGS results, quantitative polymerase chain reaction (qPCR) and Sanger sequencing were performed to resolve the adjudicated discrepancy. Results IDH1/2 NGS results differ from IHC (7/13 samples) as well as MLPA reports (1/4 samples). All NGS findings were confirmed by qPCR and Sanger sequencing. WHO CNS5 requires assessment of multiple mutations for glioma classification. Conclusions We demonstrated that qPCR or NGS performed in reference genetic laboratories, rather than IHC, is the most reliable method for IDH1/2 analysis. Clinicians should be aware of discrepancies in MLPA or IHC results and seek reconsultation in facilities with extensive access to advanced molecular technologies. Moreover, we proposed a new algorithm for the molecular diagnostic procedures in glioma patients based on the WHO CNS5. Graphical abstract

Stereotactic biopsy of posterior fossa lesions is often regarded as hazardous due to the critical structures in that area. Therefore, the aim of the study was to evaluate the diagnostic accuracy and safety of infratentorial stereotactic biopsy of brainstem or cerebellar lesions and its associations with other clinical, laboratory, and radiological parameters. From January 2000 to May 2021, 190 infratentorial stereotactic biopsies of posterior fossa tumors, including 108 biopsies of brainstem lesions, were performed. Moreover, 63 supratentorial biopsies of cerebral peduncle lesions were analyzed to compare the safety and efficacy of both approaches. Additionally, the presence of antibodies against Toxoplasma gondii and Epstein–Barr Virus (EBV) were documented in 67 and 66 patients, respectively, and magnetic resonance imaging (MRI) scans were evaluated in 114 patients. Only 4% of patients had minor complications and 1.5% had major complications, including one patient who died from intracranial bleeding. Nine (4.7%) biopsies were non-diagnostic. Isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed in 29 patients, and were non-diagnostic in only 3 (10.3%) cases. Patients with high-grade gliomas (HGG) were more frequently seropositive for T. gondii than individuals with low-grade gliomas (LGG; p < 0.001). A total of 27% of HGG and 41% of LGG were non-enhancing on MRI. The infratentorial approach is generally safe and reliable for biopsy of brainstem and cerebellar lesions. In our study, the safety and efficacy of supratentorial biopsy of the cerebral peduncle and infratentorial biopsy of lesions below the cerebral peduncle were comparably high. Moreover, patients with HGG were more frequently seropositive for T. gondii than patients with LGG, and the relationship between toxoplasmosis and gliomagenesis requires further investigation.

Gliomas are the most common primary central nervous system tumors; despite recent advances in diagnosis and treatment, glioma patients generally have a poor prognosis. Hence there is a clear need for improved therapeutic options. In recent years, significant effort has been made to investigate immunotherapy and precision oncology approaches. The review covers well-established strategies such as surgery, temozolomide, PCV, and mTOR inhibitors. Furthermore, it summarizes promising therapies: tumor treating fields, immune therapies, tyrosine kinases inhibitors, IDH(Isocitrate dehydrogenase)-targeted approaches, and others. While there are many promising treatment strategies, none fundamentally changed the management of glioma patients. However, we are still awaiting the outcome of ongoing trials, which have the potential to revolutionize the treatment of glioma.