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Background. Patients with recurrent high-grade glioma (HGG) have a poor prognosis and there is no defined standard of care. High levels of vascular endothelial growth factor (VEGF) expressed in HGG make the anti-VEGF monoclonal antibody bevacizumab (BEV) of particular interest. Patients and methods. In an ongoing registry data were collected from patients who have received BEV for the treatment of recurrent HGG. The primary objective was the identification of any clinical benefit as assessed by change in Karnofsky Performance Score (KPS), decreased steroid use and duration of treatment. Results. Two hundred and twenty-five patients with HGG were included (176 glioblastoma; 49 anaplastic glioma; median age 52 years). KPS improved in 10% of patients and remained stable in 68%. Steroids were stopped in 37.6% of patients. Median duration of treatment was 5.5 months; 19.1% of patients were treated for more than 12 months. Median overall survival from beginning of BEV treatment was 8.5 months. At the time of analysis, 169 patients (75.1%) had died and 56 patients (24.9%) were alive. Only 21 patients (9.3%) discontinued treatment due to toxicity. Conclusions. Our data reveal valuable palliation with preservation of KPS and an option for steroid withdrawal in patients treated with BEV, supporting the role of this therapy in late-stage disease. [ABSTRACT FROM AUTHOR]

The article offers information on a study conducted to analyze whether antiepilectic drugs (AEDs) have affect on serum levels of vitamin B12 and folate. The study included patients who suffered from epilepsy of the Department for Epileptology of the University Hospital Bonn in Germany. It mentions that the study conducted in Germany concluded that AEDS other than benzodiazepines and levetiracetam are associated with lower serum levels.

Background: Gadolinium-based contrast agents (GBCAs) are widely used to enhance tissue contrast during MRI scans and play a crucial role in the management of patients with cancer. However, studies have shown gadolinium deposition in the brain after repeated GBCA administration with yet unknown clinical significance. We aimed to assess the feasibility and diagnostic value of synthetic post-contrast T1-weighted MRI generated from pre-contrast MRI sequences through deep convolutional neural networks (dCNN) for tumour response assessment in neuro-oncology., Methods: In this multicentre, retrospective cohort study, we used MRI examinations to train and validate a dCNN for synthesising post-contrast T1-weighted sequences from pre-contrast T1-weighted, T2-weighted, and fluid-attenuated inversion recovery sequences. We used MRI scans with availability of these sequences from 775 patients with glioblastoma treated at Heidelberg University Hospital, Heidelberg, Germany (775 MRI examinations); 260 patients who participated in the phase 2 CORE trial (1083 MRI examinations, 59 institutions); and 505 patients who participated in the phase 3 CENTRIC trial (3147 MRI examinations, 149 institutions). Separate training runs to rank the importance of individual sequences and (for a subset) diffusion-weighted imaging were conducted. Independent testing was performed on MRI data from the phase 2 and phase 3 EORTC-26101 trial (521 patients, 1924 MRI examinations, 32 institutions). The similarity between synthetic and true contrast enhancement on post-contrast T1-weighted MRI was quantified using the structural similarity index measure (SSIM). Automated tumour segmentation and volumetric tumour response assessment based on synthetic versus true post-contrast T1-weighted sequences was performed in the EORTC-26101 trial and agreement was assessed with Kaplan-Meier plots., Findings: The median SSIM score for predicting contrast enhancement on synthetic post-contrast T1-weighted sequences in the EORTC-26101 test set was 0·818 (95% CI 0·817-0·820). Segmentation of the contrast-enhancing tumour from synthetic post-contrast T1-weighted sequences yielded a median tumour volume of 6·31 cm 3 (5·60 to 7·14), thereby underestimating the true tumour volume by a median of -0·48 cm 3 (-0·37 to -0·76) with the concordance correlation coefficient suggesting a strong linear association between tumour volumes derived from synthetic versus true post-contrast T1-weighted sequences (0·782, 0·751-0·807, p<0·0001). Volumetric tumour response assessment in the EORTC-26101 trial showed a median time to progression of 4·2 months (95% CI 4·1-5·2) with synthetic post-contrast T1-weighted and 4·3 months (4·1-5·5) with true post-contrast T1-weighted sequences (p=0·33). The strength of the association between the time to progression as a surrogate endpoint for predicting the patients' overall survival in the EORTC-26101 cohort was similar when derived from synthetic post-contrast T1-weighted sequences (hazard ratio of 1·749, 95% CI 1·282-2·387, p=0·0004) and model C-index (0·667, 0·622-0·708) versus true post-contrast T1-weighted MRI (1·799, 95% CI 1·314-2·464, p=0·0003) and model C-index (0·673, 95% CI 0·626-0·711)., Interpretation: Generating synthetic post-contrast T1-weighted MRI from pre-contrast MRI using dCNN is feasible and quantification of the contrast-enhancing tumour burden from synthetic post-contrast T1-weighted MRI allows assessment of the patient's response to treatment with no significant difference by comparison with true post-contrast T1-weighted sequences with administration of GBCAs. This finding could guide the application of dCNN in radiology to potentially reduce the necessity of GBCA administration., Funding: Deutsche Forschungsgemeinschaft., Competing Interests: Declaration of interests SH reports grants from the German Research Council and Dietmar-Hopp Foundation, outside of the submitted work. JD reports grants from ViewRay, the Clinical Research Institute, Accuray, RaySearch Laboratories, Vision RT, Merck, Astellas Pharma, AstraZeneca, Siemens Healthcare, Solution Akademie, Egomed, Quintiles, Pharmaceutical Research Association, Boehringer Ingelheim, PTW-Freiburg, and Nanobiotix, outside of the submitted work. MP reports non-financial support from Pfizer, and grants and personal fees from Bayer, outside of the submitted work. MP also has a licensed patent for IDH1 vaccines, a patent H3 vaccine pending, and a patent AHR inhibitor with royalties paid to Bayer. AI reports grants and travel funding from Carthera; research grants from Transgene, Sanofi, Air Liquide, and Nutritheragene; travel funding from Leo Pharma; and is on the advisory board for Novocure and Leo Pharma, outside the submitted work. MjvdB reports personal fees from Roche, Cellgene, Bristol Myers Squibb, Agios, Merck Sharpe & Dohme, and Boehringer Ingelheim; and grants and personal fees from AbbVie, outside of the submitted work. BN is on the scientific advisory board for Karyopharm and BTG Pharmaceuticals and is on the data safety and monitoring board for the University of Pennsylvania (Philadelphia, PA, USA), outside of the submitted work. J-CT reports personal fees from BrainLab and carThera, outside of the submitted work. WW reports grants from Apogenix, Boehringer Ingelheim, and Pfizer; grants and personal fees from Merck Sharp and Dohme and Roche; and personal fees from Bristol Myers Squibb and Celldex, outside of the submitted work. MB reports personal fees from Boehringer Ingelheim, Merck, Bayer, Teva, B Braun, Springer, and Vascular Dynamics; grants and personal fees from Novartis, Codman, and Guerbet; and grants from Siemens, Hopp Foundation, the German Research Council, the EU, Stryker, and Medtronic, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aim of the Study: Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O 6 -methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma., Methods: MGMT promoter methylation and TERT promoter mutation status were retrospectively assessed in a prospective cohort of patients with IDH-wild-type glioblastoma of the German Glioma Network (GGN) (n = 298) and an independent retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n = 302)., Results: In the GGN cohort, but not in the Düsseldorf/Zurich cohort, TERT promoter mutation was moderately associated with inferior outcomes in patients with MGMT promoter-unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07-2.82; p = 0.026). TERT promoter mutations were not associated with better outcomes in patients with MGMT promoter-methylated tumours in either cohort. The two different TERT promoter hotspot mutations (C228T and C250T) were not linked to distinct outcomes., Conclusions: Analysis of two independent cohorts of patients with glioblastoma did not confirm previous data, suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in patients with IDH-wild-type glioblastoma., Competing Interests: Conflict of interest statement P.R. has received honoraria for advisory board participation and lectures from Bristol-Myers Squibb (BMS), Debiopharm, Medac, Merck, MSD, Novocure, QED and Roche. T.P. has received honoraria for lectures from Chugai, Tokyo, and Mayo Clinic, Rochester. M.S. has received honoraria for consulting from Novocure and Integra. Mi.W. has received research grants from AbbVie, Adastra, Dracen, Merck Sharp & Dohme (MSD), Merck (EMD) and Novocure and honoraria for lectures or advisory board participation or consulting from AbbVie, Basilea, BMS, Celgene, Medac, MSD, Merck (EMD), Nerviano Medical Sciences, Orbus, Roche and Tocagen. G.R. has received honoraria for advisory board participations from AbbVie. The other authors report no disclosures., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The prognosis for glioma remains dismal, and little is known about the final disease phase. To obtain information about this period, we surveyed caregivers of patients who were registered in the German Glioma Network and who died from the disease., Methods: A questionnaire with 15 items, focusing on medical, logistic, and mental health support and symptom control during the final 4 weeks, was sent to caregivers. For some of the questions, a scale from 1 (inadequate) to 10 (excellent) was used., Results: Of 1655 questionnaires, 605 were returned (36.6%) and evaluated. We found that 67.9% of the patients were taken care of at home for the last 4 weeks; 47.7% died at home, 22.6% died in hospitals, and 19.3% died in hospice facilities. Medical support was provided by general practitioners in 72.3% of cases, by physicians affiliated with a nursing home or hospice in 29.9%, and by general oncologists in 17%. Specialized neuro-oncologists were involved in 6%. The caregivers ranked the medical support with a mean of 7.2 (using a 10-point scale), nursing service with 8.1, and mental health support with 5.5. In 22.9% of cases, no support for the caregivers themselves was offered by medical institutions., Conclusions: Although these data reflect the caregivers' subjective views, they are useful in understanding and improving current patterns of care. While patients and their caregivers are supported mainly by neuro-oncologists for most of the disease phase, the end-of-life phase is managed predominantly by general practitioners and specialists in palliative care. Close cooperation between these specialties is necessary to meet the specific needs of glioma patients.

Carbamazepine (CBZ), caffeine and cetirizine were monitored by enzyme-linked immunosorbent assays (ELISAs) in surface and wastewaters from Berlin, Germany. This fast and cost-efficient method enabled to assess the spatial and temporal variation of these anthropogenic markers in a high-throughput screening. CBZ and cetirizine were detected by the same antibody, which selectively discriminates between both compounds depending on the pH value used in the incubation step. To our best knowledge, this is the first dual-analyte immunoassay working with a single antibody. The frequent sampling with 487 samples being processed allowed for the repeated detection of unusually high concentrations of CBZ and caffeine. ELISA results correlate well with the ones obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Caffeine concentrations found in surface waters were elevated by combined sewer overflows after stormwater events. During the hay fever season, the concentrations of the antihistamine drug cetirizine increased in both surface and wastewaters. Caffeine was almost completely removed during wastewater treatment, while CBZ and cetirizine were found to be more persistent. The maximum concentrations of caffeine, CBZ and cetirizine found in influent wastewater by LC-MS/MS were 470, 5.0 and 0.49 μg L(-1), while in effluent wastewater the concentrations were 0.22, 4.5 and 0.51 μg L(-1), respectively. For surface waters, concentrations up to 3.3, 4.5 and 0.72 μg L(-1) were found, respectively., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Functional genetic polymorphisms involved in folate and methionine metabolism play an important role in both DNA synthesis and methylation, and affect the risk of various malignancies including lymphoproliferative disorders such as systemic non-Hodgkin's lymphoma. In a retrospective analysis of 185 immunocompetent patients with primary central nervous system lymphoma (PCNSL) and 212 population controls we therefore investigated eight genetic polymorphisms affecting methionine metabolism for potential association with the development of PCNSL. We observed underrepresentation of the G-allele of the methyltetrahydrofolate homocysteine S-methyltransferase (MTR) c.2756A > G (D919G) missense polymorphism among PCNSL patients (P = 0.045; odds ratio (OR) = 0.65; 0.43-0.99). Furthermore, for the methylenetetrahydrofolate reductase (MTHFR) c.1298A > C (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients than among population controls (P = 0.026; OR = 1.57; 1.05-2.34). There were no associations of the other polymorphisms investigated (MTHFR c.677C > T, transcobalamin 2 (Tc2) c.776C > G, cystathionin beta-synthase (CBS) c.844&#95;855ins68, reduced folate carrier-1 (RFC-1) c.80G > A, thymidylate synthase (TYMS) 28-bp repeat, and dihydrofolate reductase (DHFR) c.594 + 59del19 bp) and the presence of PCNSL. This analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL. Our results suggest the hypothesis that folate and methionine metabolism is relevant to susceptibility to PCNSL.

Human leukocyte antigens (HLA) are involved in the regulation of immune response to infection and in malignant transformation. Several HLA alleles are associated with immunological or malignant diseases. The aim of the present study was to evaluate a potential association of HLA class I and II alleles with primary central nervous system lymphoma (PCNSL) in immunocompetent patients. We therefore analyzed particular HLA-A, HLA-B and HLA-DRB1 alleles in 82 PCNSL patients and compared the data to those in 327 population controls. No significant difference between these two groups was found using Pearson's chi(2) test. These data do not support the hypothesis that HLA alleles play a major role in the pathogenesis of PCNSL.