Appearance Of Glioblastoma Research Articles

Cerebral Glioblastoma: A Review on Genetic Alterations, Signaling Pathways, and Clinical Managements

Context: Glioblastoma, previously known as glioblastoma multiforme (GBM), is a grade IV astrocytoma that frequently affects patients with a mean age of 45 and above. It is generally categorized into primary and secondary subtypes, based on research conducted by Hans Joachim Scherer. Evidence Acquisition: This review concentrates on cellular and genetic drawbacks that can lead to the appearance of glioblastoma. National Center for Biotechnology Information (NCBI) was the main source used for writing this review article, followed by Google scholar. The following keywords were used to retrieve articles: 'glioblastoma', 'brain tumors', 'glioma', 'LOH', and 'cellular and signaling pathways in glioblastoma'. Results: Several genetic alterations and cellular pathways are involved in the appearance and progression of glioblastoma, including loss of heterozygosity (LoH), TP53 mutation, isocitrate dehydrogenase 1 (IDH1) mutation, P16INK4/RB1 pathway, and EGFR/PTEN/Akt/mTOR pathway. The majority (70%) of primary glioblastomas are caused by (LoH), and it mostly occurs in older people. Secondary glioblastoma is mainly manifested by TP53 mutation and usually affects younger people. Understanding the alterations and cellular mechanisms involved in glioblastoma is important to develope new therapeutic regimes. Surgery, radiation therapy, temozolomide, and TTFields are the four most important therapeutic options available for treating patients. Conclusions: In this review, the genetic alterations and cellular pathways which could lead to the appearance of this tumor were highlighted, and the latest options for treating patients dealing with glioblastoma were discussed.

Exploratory Analysis of Qualitative MR Imaging Features for the Differentiation of Glioblastoma and Brain Metastases.

ObjectivesTo identify qualitative VASARI (Visually AcceSIble Rembrandt Images) Magnetic Resonance (MR) Imaging features for differentiation of glioblastoma (GBM) and brain metastasis (BM) of different primary tumors.Materials and MethodsT1-weighted pre- and post-contrast, T2-weighted, and T2-weighted, fluid attenuated inversion recovery (FLAIR) MR images of a total of 239 lesions from 109 patients with either GBM or BM (breast cancer, non-small cell (NSCLC) adenocarcinoma, NSCLC squamous cell carcinoma, small-cell lung cancer (SCLC)) were included. A set of adapted, qualitative VASARI MR features describing tumor appearance and location was scored (binary; 1 = presence of feature, 0 = absence of feature). Exploratory data analysis was performed on binary scores using a combination of descriptive statistics (proportions with 95% binomial confidence intervals), unsupervised methods and supervised methods including multivariate feature ranking using either repeated fitting or recursive feature elimination with Support Vector Machines (SVMs).ResultsGBMs were found to involve all lobes of the cerebrum with a fronto-occipital gradient, often affected the corpus callosum (32.4%, 95% CI 19.1–49.2), and showed a strong preference for the right hemisphere (79.4%, 95% CI 63.2–89.7). BMs occurred most frequently in the frontal lobe (35.1%, 95% CI 28.9–41.9) and cerebellum (28.3%, 95% CI 22.6–34.8). The appearance of GBMs was characterized by preference for well-defined non-enhancing tumor margin (100%, 89.8–100), ependymal extension (52.9%, 36.7–68.5) and substantially less enhancing foci than BMs (44.1%, 28.9–60.6 vs. 75.1%, 68.8–80.5). Unsupervised and supervised analyses showed that GBMs are distinctively different from BMs and that this difference is driven by definition of non-enhancing tumor margin, ependymal extension and features describing laterality. Differentiation of histological subtypes of BMs was driven by the presence of well-defined enhancing and non-enhancing tumor margins and localization in the vision center. SVM models with optimal hyperparameters led to weighted F1-score of 0.865 for differentiation of GBMs from BMs and weighted F1-score of 0.326 for differentiation of BM subtypes.ConclusionVASARI MR imaging features related to definition of non-enhancing margin, ependymal extension, and tumor localization may serve as potential imaging biomarkers to differentiate GBMs from BMs.

Correlation of Ki-67 Index with Volumetric Segmentation and its Value as a Prognostic Marker in Glioblastoma

Previous research has shown a strong correlation between the Ki-67 proliferation index and grade of malignancy in astrocytoma. Ki-67 has also shown encouraging results as a prognostic marker for patients' overall survival (OS). We focus on whether the index is linked to the appearance of glioblastoma on pretreatment magnetic resonance imaging (MRI) or to OS. In our retrospective study, only isocitrate dehydrogenase IDH wild-type glioblastoma was included (n= 152). Ki-67 index was quantified via immunohistochemistry. On all pretreatment MRI, tumor compartments (tumor, necrosis, and edema) were volumetrically assessed. An OS subpopulation was filtered from the total cohort (residual tumor volume ≤2 cm3). In addition, a propensity score matching was executed. All volumetric assessed tumor volumes correlated with each other (P ≤ 0.011), although the Ki-67 index showed no correlation with any of the measured volumes. Concerning the OS, a cutoff value of 20% for the Ki-67 index showed a significant influence on patients' OS in multivariate analysis (P= 0.043). The unique appearance of every glioblastoma on MRI seems to be independent of the Ki-67 index. Furthermore, the Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 20% for Ki-67.

A Multiparametric Model for Mapping Cellularity in Glioblastoma Using Radiographically Localized Biopsies.

The complex MR imaging appearance of glioblastoma is a function of underlying histopathologic heterogeneity. A better understanding of these correlations, particularly the influence of infiltrating glioma cells and vasogenic edema on T2 and diffusivity signal in nonenhancing areas, has important implications in the management of these patients. With localized biopsies, the objective of this study was to generate a model capable of predicting cellularity at each voxel within an entire tumor volume as a function of signal intensity, thus providing a means of quantifying tumor infiltration into surrounding brain tissue. Ninety-one localized biopsies were obtained from 36 patients with glioblastoma. Signal intensities corresponding to these samples were derived from T1-postcontrast subtraction, T2-FLAIR, and ADC sequences by using an automated coregistration algorithm. Cell density was calculated for each specimen by using an automated cell-counting algorithm. Signal intensity was plotted against cell density for each MR image. T2-FLAIR (r = -0.61) and ADC (r = -0.63) sequences were inversely correlated with cell density. T1-postcontrast (r = 0.69) subtraction was directly correlated with cell density. Combining these relationships yielded a multiparametric model with improved correlation (r = 0.74), suggesting that each sequence offers different and complementary information. Using localized biopsies, we have generated a model that illustrates a quantitative and significant relationship between MR signal and cell density. Projecting this relationship over the entire tumor volume allows mapping of the intratumoral heterogeneity in both the contrast-enhancing tumor core and nonenhancing margins of glioblastoma and may be used to guide extended surgical resection, localized biopsies, and radiation field mapping.

Impact of adjuvant anti-VEGF therapy on treatment-related pseudoprogression in patients with newly diagnosed glioblastoma receiving chemoradiation with or without anti-VEGF therapy.

2025 Background: Chemoradiation (CRT) can significantly modify the appearance of glioblastoma (GBM) on MRI, especially within the 3-month window after CRT. Pseudoprogression (PsP) is an increasingly recognized phenomenon in this scenario, and is thought to be secondary to increased permeability of the tumor vessels from irradiation, possibly enhanced by temozolomide (TMZ). We sought to determine if the addition of a VEGF signaling inhibitor (cediranib) during and after CRT had an impact on the frequency of PsP, by comparing two groups of patients with newly diagnosed GBMs. Methods: Two groups of patients enrolled in IRB-approved trials underwent serial MRIs at baseline, weekly during CRT and monthly thereafter. The control group received radiation plus TMZ, while the other group (CED) also received cediranib until progression (which was defined by RANO criteria) or toxicity. Patients that progressed up to 3 months after CRT were considered to have apparent progression (AP) and kept on treatment. Lesions that subsequently stabilized/regressed were classified as PsP, while those that maintained growth despite treatment were classified as true early progression (EP). Results: Forty patients were enrolled in CED and 11 as controls. Ten patients from CED and three controls were excluded due to treatment discontinuation before 3 months (drug-related toxicity and enrollment in post-CRT trials respectively). Three patients in CED (6%) had AP (all confirmed as EP) and no patients fulfilled criteria for PsP. Six patients from control (54%) had AP; 3 (27%) were eventually classified as EP and 3 (27%) as PsP. The frequency of PsP was significantly higher in the control group (p=0.0086). Conclusions: The addition of a VEGF inhibitor as part of adjuvant treatment in this cohort of glioblastoma patients prevented the development of early treatment-related effects (PsP). Suppressing the edema and mass effect that accompanies PsP may improve the tolerability of treatment. Additionally, this effect may be exploited as a strategy to make chemoradiation feasible in patients with large, unresectable tumors and/or poor baseline performance status.

Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria

Tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We generated cell lines from glioblastoma specimens with the goal to obtain model systems for glioma stem cell biology. Unsupervised analysis of the expression profiles of nine cell lines established under neural stem cell conditions yielded two distinct clusters. Four cell lines were characterized by the expression of neurodevelopmental genes. They showed a multipotent differentiation profile along neuronal, astroglial and oligodendroglial lineages, grew spherically in vitro, expressed CD133 and formed highly invasive tumors in vivo. The other five cell lines shared expression signatures enriched for extracellular matrix-related genes, had a more restricted differentiation capacity, contained no or fewer CD133+ cells, grew semiadherent or adherent in vitro and displayed reduced tumorigenicity and invasion in vivo. Our findings show that stable, multipotent glioblastoma cell lines with a full stem-like phenotype express neurodevelopmental genes as a distinctive feature, which may offer therapeutic targeting opportunities. The generation of another distinct cluster of cell lines showing similarly homogeneous profiling but restricted stem cell properties suggests that different phenotypes exist, each of which may lead to the typical appearance of glioblastoma.

Importance of diffusion-weighted imaging in the diagnosis of cystic brain tumors and intracerebral abscesses

Objective It is often difficult to decide whether a cystic brain lesion is a tumor or an abscess by means of conventional MRI techniques. The immediate diagnosis of a brain abscess is important for the patient's outcome. Our goal was to study the ability of diffusion-weighted imaging and calculation of the apparent diffusion coefficient (ADC) to differentiate between these two pathologies. Patients and methods Ten patients (five men, five women) with cystic brain lesions were examined with MRI. The ADC maps were calculated for each subject and the ADC value of each lesion was measured. Histology revealed glioblastoma multiforme in six patients and abscess in four patients. Results All brain abscesses showed markedly hyperintense signal changes on diffusion-weighted imaging, whereas the appearance of glioblastoma varied from slightly hyperintense to hypointense signal conversion. The mean ADC value calculated in the six patients with cystic brain tumor was: 2.05×10-3 mm2/s (1.38-2.88×10-3 mm2/s). The mean ADC value of the four patients with brain abscess was: 0.57×10-3 mm2/s (0.38-0.77×10-3 mm2/s). Conclusion Diffusion-weighted imaging and calculation of ADC maps constitute a helpful tool to differentiate between cystic brain tumors and brain abscesses.

Importance of Diffusion-Weighted Imaging in the Diagnosis of Cystic Brain Tumors and Intracerebral Abscesses

It is often difficult to decide whether a cystic brain lesion is a tumor or an abscess by means of conventional MRI techniques. The immediate diagnosis of a brain abscess is important for the patient's outcome. Our goal was to study the ability of diffusion-weighted imaging and calculation of the apparent diffusion coefficient (ADC) to differentiate between these two pathologies. Ten patients (five men, five women) with cystic brain lesions were examined with MRI. The ADC maps were calculated for each subject and the ADC value of each lesion was measured. Histology revealed glioblastoma multiforme in six patients and abscess in four patients. All brain abscesses showed markedly hyperintense signal changes on diffusion-weighted imaging, whereas the appearance of glioblastoma varied from slightly hyperintense to hypointense signal conversion. The mean ADC value calculated in the six patients with cystic brain tumor was: 2.05 x 10 (-3) mm(2)/s (1.38-2.88 x 10 (-3) mm(2)/s). The mean ADC value of the four patients with brain abscess was: 0.57 x 10 (-3) mm(2)/s (0.38-0.77 x 10 (-3) mm(2)/s). Diffusion-weighted imaging and calculation of ADC maps constitute a helpful tool to differentiate between cystic brain tumors and brain abscesses.

The treatment of adult supratentorial high grade astrocytomas.

From 1 January, 1982 until 31 December, 1987 260 adult patients were referred to the Cancer Control Agency of B.C. with high grade supratentorial astrocytomas. Multifocal disease on presentation was present in 17 cases (6.5%). Their survival is poor and whole brain radiotherapy is required. All other cases had unifocal disease, but eight did not receive radiotherapy. The 235 cases who received radiotherapy were subject to univariate and multivariate analyses according to extent of surgery, age, Kernohan and WHO grading, Karnofsky performance status, whole brain treatment, partial brain treatment, total dose and neuroret. Age is an extremely important predictor of survival (P approximately equal to 0). The pathologic appearance of glioblastoma (WHO grade) as well as the Karnofsky performance status were also important independent factors in predicting survival (P = 0.016, 0.027 respectively) on Cox multivariate analysis. Dose and neurorets were significant factors only in cases where the performance status was not recorded, suggesting that dose was selected according to the patient's condition and age. In this analysis it was found that localized radiation fields may be used rather than whole brain without jeopardizing survival.

Glioblastoma with extracranial metastasis through ventriculopleural shunt. Case report.

✓ Extracranial metastasis of an intracranial glioblastoma through a ventriculopleural shunt to the right thorax is reported in a 22-year-old man following a ventriculopleural shunt and telecobalt therapy. Autopsy 8 months after the shunt showed cerebral tumor involving the ventricular system, and irregularly thickened pleura in the right thorax. The primary intracranial tumor and the tumor located extracranially showed the same morphological appearance of glioblastoma.