Improving the utility of 1 H-MRS for the differentiation of glioma recurrence from radiation necrosis

Abstract

Proton magnetic resonance spectroscopy (¹H-MRS) has shown promise in distinguishing recurrent high-grade glioma from posttreatment radiation effect (PTRE). The purpose of this study was to establish objective ¹H-MRS criteria based on metabolite peak height ratios to distinguish recurrent tumor (RT) from PTRE. A retrospective analysis of magnetic resonance imaging and ¹H-MRS data was performed. Spectral metabolites analyzed included N-acetylaspartate, choline (Cho), creatine (Cr), lactate (Lac), and lipids (Lip). Quantitative ¹H-MRS criteria to differentiate RT from PTRE were identified using 81 biopsy-matched spectral voxels. A receiver operating characteristic curve analysis was conducted for all metabolite ratio combinations with the pathology diagnosis as the classification variable. Forward discriminant analysis was used to identify ratio variables that maximized the correct classification of RT versus PTRE. Our results were applied to 205 records without biopsy-matched voxels to examine the percent agreement between our criteria and the radiologic diagnoses. Five ratios achieved an acceptable balance [area under the curve (AUC) ≥ 0.700] between sensitivity and specificity for distinguishing RT from PTRE, and each ratio defined a criterion for diagnosing RT. The ratios are as follows: Cho/Cr > 1.54 (sensitivity 66%, specificity 79%), Cr/Cho ≤ 0.63 (sensitivity 65%, specificity 79%), Lac/Cho ≤ 2.67 (sensitivity 85%, specificity 58%), Lac/Lip ≤ 1.64 (sensitivity 54%, specificity 95%), and Lip/Lac > 0.58 (sensitivity 56%, specificity 95%). Application of our ratio criteria in prospective studies may offer an alternative to biopsy or visual spectral pattern recognition to distinguish RT from PTRE in patients with gliomas.

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Ischemic stroke and intracranial hemorrhage in patients with recurrent glioblastoma multiforme, treated with bevacizumab

Abstract

Bevacizumab (BVZ), a monoclonal antibody directed against vascular endothelial growth factor (VEGF), has been suspected to increase the incidence of ischemic stroke (IS) and intracranial hemorrhage (ICH) in GBM patients. Intracranial vascular events, such as IS and ICH, were retrospectively analyzed in 364 MRI scans of 82 patients with recurrent GBM (1st/2nd/3rd relapse). Out of these 82 patients, 40 were treated with BVZ (178 scans) in addition to basic treatment, whereas 42 patients matching for age and gender received basic treatment (186 scans). Distribution of typical vascular risk factors between both groups was analyzed retrospectively. In seven out of 82 patients (8%) vascular events were detected in MRI. Four vascular events were recorded in the BVZ-group (3 IS and 1 ICH), and 3 vascular events were found in the Control-group (1 IS and 2 ICH; p > 0.05 between both groups). Likewise, vascular risk factors (arterial hypertension, diabetes mellitus, obesity, former vascular event, hyperlipidemia, tobacco consumption and/or hypercholesterolemia) did not differ significantly between both groups. BVZ treatment does not seem to be associated with an increased risk for vascular events in patients with GBM in recurrence.

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Ethical considerations of neuro-oncology trial design in the era of precision medicine

Abstract

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

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Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells

Abstract

DEP domain containing 1 (DEPDC1) is a novel oncoantigen expressed in cancer cells, which presents oncogenic activity and high immunogenicity. Although DEPDC1 has been predicted to be a useful antigen for the development of a cancer vaccine, its pathophysiological roles in glioma have not been investigated. Here, we analyzed the expression and function of DEPDC1 in malignant glioma. DEPDC1 expression in glioma cell lines, glioma tissues, and brain tumor initiating cells (BTICs) was assessed by western blot and quantitative polymerase chain reaction (PCR). The effect of DEPDC1 downregulation on cell growth and nuclear factor kappa B (NFκB) signaling in glioma cells was investigated. Overall survival was assessed in mouse glioma models using human glioma cells and induced mouse brain tumor stem cells (imBTSCs) to determine the effect of DEPDC1 suppression in vivo. DEPDC1 expression was increased in glioma cell lines, tissues, and BTICs. Suppression of endogenous DEPDC1 expression by small interfering RNA (siRNA) inhibited glioma cell viability and induced apoptosis through NFκB signaling. In mouse glioma models using human glioma cells and imBTSCs, downregulation of DEPDC1 expression prolonged overall survival. These results suggest that DEPDC1 represents a target molecule for the treatment of glioma.

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Professor Enrico Mihich, 1928–2016

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Ischemic stroke and intracranial hemorrhage in patients with recurrent glioblastoma multiforme, treated with bevacizumab

Abstract

Bevacizumab (BVZ), a monoclonal antibody directed against vascular endothelial growth factor (VEGF), has been suspected to increase the incidence of ischemic stroke (IS) and intracranial hemorrhage (ICH) in GBM patients. Intracranial vascular events, such as IS and ICH, were retrospectively analyzed in 364 MRI scans of 82 patients with recurrent GBM (1st/2nd/3rd relapse). Out of these 82 patients, 40 were treated with BVZ (178 scans) in addition to basic treatment, whereas 42 patients matching for age and gender received basic treatment (186 scans). Distribution of typical vascular risk factors between both groups was analyzed retrospectively. In seven out of 82 patients (8%) vascular events were detected in MRI. Four vascular events were recorded in the BVZ-group (3 IS and 1 ICH), and 3 vascular events were found in the Control-group (1 IS and 2 ICH; p > 0.05 between both groups). Likewise, vascular risk factors (arterial hypertension, diabetes mellitus, obesity, former vascular event, hyperlipidemia, tobacco consumption and/or hypercholesterolemia) did not differ significantly between both groups. BVZ treatment does not seem to be associated with an increased risk for vascular events in patients with GBM in recurrence.

from Cancer via ola Kala on Inoreader http://ift.tt/2quWG24
via IFTTT

Improving the utility of 1 H-MRS for the differentiation of glioma recurrence from radiation necrosis

Abstract

Proton magnetic resonance spectroscopy (¹H-MRS) has shown promise in distinguishing recurrent high-grade glioma from posttreatment radiation effect (PTRE). The purpose of this study was to establish objective ¹H-MRS criteria based on metabolite peak height ratios to distinguish recurrent tumor (RT) from PTRE. A retrospective analysis of magnetic resonance imaging and ¹H-MRS data was performed. Spectral metabolites analyzed included N-acetylaspartate, choline (Cho), creatine (Cr), lactate (Lac), and lipids (Lip). Quantitative ¹H-MRS criteria to differentiate RT from PTRE were identified using 81 biopsy-matched spectral voxels. A receiver operating characteristic curve analysis was conducted for all metabolite ratio combinations with the pathology diagnosis as the classification variable. Forward discriminant analysis was used to identify ratio variables that maximized the correct classification of RT versus PTRE. Our results were applied to 205 records without biopsy-matched voxels to examine the percent agreement between our criteria and the radiologic diagnoses. Five ratios achieved an acceptable balance [area under the curve (AUC) ≥ 0.700] between sensitivity and specificity for distinguishing RT from PTRE, and each ratio defined a criterion for diagnosing RT. The ratios are as follows: Cho/Cr > 1.54 (sensitivity 66%, specificity 79%), Cr/Cho ≤ 0.63 (sensitivity 65%, specificity 79%), Lac/Cho ≤ 2.67 (sensitivity 85%, specificity 58%), Lac/Lip ≤ 1.64 (sensitivity 54%, specificity 95%), and Lip/Lac > 0.58 (sensitivity 56%, specificity 95%). Application of our ratio criteria in prospective studies may offer an alternative to biopsy or visual spectral pattern recognition to distinguish RT from PTRE in patients with gliomas.

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via IFTTT