CA9, CYFIP2 and LGALS3BP-A Novel Biomarker Panel to Aid Prognostication in Glioma.

Brain cancer is a devastating and life-changing disease. Biomarkers are becoming increasingly important in addressing clinical issues, including in monitoring tumour progression and assessing survival and treatment response. The goal of this study was to identify prognostic biomarkers associated with glioma progression.

PSMA Expression Correlates with Improved Overall Survival and VEGF Expression in Glioblastoma.

Background: Glioblastomas are the most common and fatal primary brain malignancy in adults. There is a growing interest in identifying the molecular mechanisms of these tumors to develop novel treatments. Glioblastoma neo-angiogenesis is driven by VEGF, and another potential molecule linked to angiogenesis is PSMA.

Implications of Concurrent and Mutations on Survival in Glioma-A Case Report and Systematic Review.

Both (isocitrate dehydrogenase 1) and (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular metabolic processes. Here we describe a case of a patient with an IDH-mutant astrocytoma, in which both and mutations were detected within the same tumour. The patient remains disease-free, nine and a half years after her initial diagnosis.

The use of Sonidegib in the adjuvant and advanced phases of Sonic Hedge Hog Mutant Medulloblastomas.

Medulloblastomas are rare embryonal primary brain tumours originating in the cerebellum. Most medulloblastomas arising in adults are associated with mutations in the Sonic Hedge Hog (SHH) pathway. Patient 1 was prescribed Sonidegib for recurrent metastatic SHH mutated medulloblastoma multiple lines of treatment.

Differential effects of radiation fractionation regimens on glioblastoma.

Background: Radiotherapy (RT) is a mainstay of treatment for patients with glioblastoma (GB). Early clinical trials show that short course hypofractionation showed no survival benefit compared to conventional regimens with or without temozolomide chemotherapy (TMZ) but reduces the number of doses required. Concerns around delayed neurological deficits and reduced cognition from short course hypofractionated RT remain a concern.

Redo craniotomy or bevacizumab for symptomatic steroid-refractory true or pseudoprogression following IMRT for glioblastoma.

Background: There is minimal evidence to support decision making for symptomatic steroid-refractory pseudoprogression or true progression occurring after intensity-modulated radiation therapy (IMRT) for glioblastoma (GBM). This study audited the survival outcome of patients managed with redo craniotomy (RedoSx) or bevacizumab (BEV) for steroid-refractory mass effect after IMRT for GBM.

Methods: Patients with GBM managed between 2008 and 2019 with the EORTC-NCIC Protocol were entered into a prospective database.

Are In Vitro Human Blood-Brain-Tumor-Barriers Suitable Replacements for In Vivo Models of Brain Permeability for Novel Therapeutics?

Background: High grade gliomas (HGG) are incapacitating and prematurely fatal diseases. To overcome the poor prognosis, novel therapies must overcome the selective and restricted permeability of the blood-brain barrier (BBB). This study critically evaluated whether in vitro human normal BBB and tumor BBB (BBTB) are suitable alternatives to "gold standard" in vivo models to determine brain permeability.

Temporal and spatial modulation of the tumor and systemic immune response in the murine Gl261 glioma model.

Glioblastoma, the most aggressive form of glioma, has a 5-year survival rate of <5%. While radiation and immunotherapies are routinely studied in the murine Gl261 glioma model, little is known about its inherent immune response. This study quantifies the temporal and spatial localization of immune cell populations and mediators during glioma development.

Sub-acute Toxicity in Non-cancerous Tissue and Immune-Related Adverse Events of a Novel Combination Therapy for Cancer.

Brain, lung, and colon tissue experience deleterious immune-related adverse events when immune-oncological agents or radiation are administered. However, there is a paucity of information regarding whether the addition of radiation to immuno-oncological regimens exacerbates the tissue inflammatory response. We used a murine model to evaluate sub-acute tissue damage and the systemic immune response in C57Bl/6 mice when administered systemic anti-programmed cell death protein 1 (αPD-1) immunotherapy alone or in combination with stereotactic fractionated 10 gray/5 X-ray radiation to normal brain, lung or colon tissue.

FET PET in the evaluation of indeterminate brain lesions on MRI: Differentiating glioma from other non-neoplastic causes - A pilot study.

We aimed to determine the utility of FET PET in the management of indeterminate CNS lesions found on MRI. We performed a retrospective analysis of patients with FET PET at a single tertiary institution from 2011 to 2015. FET PET images were processed using usual methods and measurements taken including SUVmax, TBRmax, and analysis of dynamic series where available (Kipeak, Vdpeak, as well as tumor:background ratio for these variables).

Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment.

While treatment with surgery, radiotherapy and/or chemotherapy may prolong life for patients with glioblastoma, recurrence is inevitable. What is still being discovered is how much these treatments and recurrence of disease affect the molecular profiles of these tumors and how these tumors adapt to withstand these treatment pressures. Understanding such changes will uncover pathways used by the tumor to evade destruction and will elucidate new targets for treatment development.

Utilizing 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) to define suspected nonenhancing tumor for radiation therapy planning of glioblastoma.

Aim: The authors sought to evaluate the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and the presence of suspected nonenhancing tumors compared with standard magnetic resonance imaging (MRI).

Methods And Materials: Patients with GBM and contrast-enhanced MRI scans showing regions suspicious of nonenhancing tumor underwent postoperative FET-PET before commencing radiation therapy. Two clinical target volumes (CTVs) were created using pre- and postoperative MRI: MRI fluid-attenuated inversion recovery (FLAIR) sequences (CTV) and MRI contrast sequences with an expansion on the surgical cavity (CTV).

Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine.

Galunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor, blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g.

Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma.

Heterogeneity is a hallmark of glioblastoma with intratumoral heterogeneity contributing to variability in responses and resistance to standard treatments. Promoter methylation status of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is the most important clinical biomarker in glioblastoma, predicting for therapeutic response. However, it does not always correlate with response.

A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma.

Background: The combination of galunisertib, a transforming growth factor (TGF)-β receptor (R)1 kinase inhibitor, and lomustine was found to have antitumor activity in murine models of glioblastoma.

Methods: Galunisertib (300 mg/day) was given orally 14 days on/14 days off (intermittent dosing). Lomustine was given as approved.

Small increases in enhancement on MRI may predict survival post radiotherapy in patients with glioblastoma.

To assess impact of volumetric changes in tumour volume post chemoradiotherapy in glioblastoma. Patients managed with chemoradiotherapy between 2008 and 2011 were included. Patients with incomplete MRI sets were excluded.

Large volume re-irradiation with bevacizumab is a feasible salvage option for patients with refractory high-grade glioma.

Background: Clinical studies of re-irradiation (ReRT) for relapsed high-grade glioma (HGG) have generally reported the use of small volume ReRT techniques such as stereotactic radiosurgery in selected patients with isolated focal relapse. This study reports the outcome with large-volume ReRT to manage the more common mescenario of extensive diffuse relapse of HGG.

Methods: All HGG patients managed with an overlapping second course of radiation therapy (RT) for refractory progression of HGG between October 2009 and April 2013 were included.

Molecular heterogeneity in glioblastoma: potential clinical implications.

Glioblastomas, (grade 4 astrocytomas), are aggressive primary brain tumors characterized by histopathological heterogeneity. High-resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers.

Predictors of distress and poorer quality of life in High Grade Glioma patients.

Objective: To determine High Grade Glioma (HGG) patients' levels of distress and QOL during combined chemoradiotherapy, explore predictors of distress and QOL and prioritize patients' supportive care needs.

Methods: Patients diagnosed with HGG who were referred for combined chemoradiotherapy were recruited. Participants completed demographics and questionnaires assessing distress, function, and supportive care needs.

Correlation of MicroRNA 132 Up-regulation with an Unfavorable Clinical Outcome in Patients with Primary Glioblastoma Multiforme Treated with Radiotherapy Plus Concomitant and Adjuvant Temozolomide Chemotherapy.

Background: MicroRNA 132 (miR-132) is dysregulated in a range of human malignancies; however, its role in glioma has not been reported. The aim of this study was to profile miR-132 expression in a cohort of patients with primary glioblastoma multiforme (GBM) treated with the Stupp regimen and to correlate microRNA levels with patient outcome.

Methods: miR-132 levels relative to RNU44 were assessed by quantitative reverse transcription-polymerase chain reaction in 43 GBMs and normal brain tissue.

Expanding the spectrum of IDH1 mutations in gliomas.

Mutations in isocitrate dehydrogenase -1 or -2 (IDH1 or IDH2) are found in the majority of WHO grade II and III diffuse gliomas and secondary glioblastomas. IDH mutation screening is rapidly becoming part of the routine pathological work up of human brain tumors, providing both diagnostic and prognostic information. Here, we characterize four rare and novel IDH1 mutations identified in surgical human glioma samples: two instances of an IDH1 p.

The impact of molecular and clinical factors on patient outcome in oligodendroglioma from 20 years' experience at a single centre.

The increased chemosensitivity of oligodendroglial tumours has been associated with loss of heterozygosity (LOH) of the p arm of chromosome 1 and the q arm of chromosome 19 (LOH 1p/19q). Other clinical and molecular factors have also been identified as being prognostic and predictive of treatment outcome. We reviewed 105 patients with oligodendroglioma treated at a single centre over 20 years.