on-site-sampling-extraction-brain-tumors-for-metabolomics-lipidomics

On-Site Sampling and Extraction of Brain Tumors for Metabolomics and Lipidomics Analysis

Despite the variety of tools available for cancer diagnosis and classification, methods that enable fast and simple characterization of tumors are still ...

10th Military Research Hospital and Polyclinic

Gliomas are common brain tumours, but obtaining tissue for definitive diagnosis can be difficult. There is, therefore, interest in the use of non-invasive methods to diagnose and grade the disease. Although positron emission tomography (PET) with 18F-fluorethyltyrosine (18F-FET) can be used to differentiate between low-grade (LGG) and high-grade (HGG) gliomas, the optimal parameters to measure and their cut-points have yet to be established. We therefore assessed the value of single and dual time-point acquisition of 18F-FET PET parameters to differentiate between primary LGGs (n = 22) and HGGs (n = 24). PET examination was considered positive for glioma if the metabolic activity was 1.6-times higher than that of background (contralateral) brain, and maximum tissue-brain ratios (TBRmax) were calculated 10 and 60 min after isotope administration with their sums and differences calculated from individual time-point values. Using a threshold-based method, the overall sensitivity of PET was 97%. Several analysed parameters were significantly different between LGGs and HGGs. However, in a receiver operating characteristics analysis, TBR sum had the best diagnostic accuracy of 87% and sensitivity, specificity, and positive and negative predictive values of 100%, 72.7%, 80%, and 100%, respectively. 18F-FET PET is valuable for the non-invasive determination of glioma grade, especially when dual time-point metrics are used. TBR sum shows the greatest accuracy, sensitivity, and negative predictive value for tumour grade differentiation and is a simple method to implement. However, the cut-off may differ between institutions and calibration strategies would be useful. 

The Sum of Tumour-to-Brain Ratios Improves the Accuracy of Diagnosing Gliomas Using 18F-FET PET.

The /2 gene mutations,  loss/mutation, 1p/19q status, and  promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the  c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed the  promoter methylation status in patients with a known mutation status in codon 132 of , followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy) with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with  promoter methylation and  somatic mutation (OS = 40 months) had a better prognosis than those with  methylation alone (OS = 18 months). In patients with astrocytoma anaplasticum ( = 7) with the  p.R132H mutation and hypermethylated , the prognosis was particularly favorable (median OS = 47 months). In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The  mutation appears more relevant for the prognosis than  methylation. The  p.R132H mutation combined with  hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.

Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions.

To compare 1p/19q codeletion, MGMT promoter methylation, and IDH mutation status in stereotactic biopsy and open craniotomy specimens.

Article	Year
The Sum of Tumour-to-Brain Ratios Improves the Accuracy of Diagnosing Gliomas Using 18F-FET PET. PloS one\| PubMed ID: 26468649	2015
Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions. International journal of molecular sciences\| PubMed ID: 27834917	2016
Biomarker concordance between molecular stereotactic biopsy and open surgical specimens in gliomas. Neurologia i neurochirurgia polska\| PubMed ID: 31746452	2019

Jacek Furtak

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