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Objective: Gliosarcoma (GSC) is a rare histological variant of glioblastoma (GBM). Due to limited evidence regarding clinical, genetic and radiographic characteristics of GSC, this study aimed to analyze independent outcome predictors of GSC, and to address the differences between GSC and GBM concerning the baseline characteristics and patients' survival., Methods: Patients treated between 2001 and 2018 for the diagnosis of GBM and GSC were included in this study. Patients' records were reviewed for demographic, clinical, genetic and radiographic characteristics. Univariate, multivariate and propensity score matched analyses were performed., Results: In the GSC sub-cohort (N = 56), patients' age, preoperative clinical status, midline tumor location and tumor size were found to be independently associated with overall survival. As compared to GBM individuals (N = 1249), a temporal location (p = 0.002), presence of eccentric tumor cysts (p < 0.001), a higher ratio of TP53 staining (p = 0.002) and a lower ratio of GFAP staining (p = 0.005) were characteristic for GSC. The diagnosis of GSC was associated with a poorer survival (p = 0.002) independently of the patients' age, sex, clinical status and extent of resection, However, this association was no more significant, when enhancing the multivariate analysis with molecular-genetic characteristics (IDH1 mutation and MGMT promotor methylation status)., Discussion: Certain radiographic and molecular-genetic patterns present the distinct characteristics of GSC. There is an association between the diagnosis of GSC and a poorer outcome. This difference might be linked to different genetic alterations in GBM and GSC. Prospective studies are needed to further elucidate the characteristics of GSC and develop targeted treatment approaches for this rare variant., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an increasingly recognized neuroinflammatory syndrome that predominantly affects the pontine and cerebellar brain structures. Characteristically, patients will develop glucocorticoid-responsive brainstem disorders, demonstrate pontocerebellar contrast enhancement on magnetic resonance imaging (MRI), and exhibit an angiocentric, lymphocytic infiltrate in brain biopsies. We have presented and discussed 2 novel and challenging cases of CLIPPERS syndrome to highlight the clinical and radiological diversity of the syndrome., Case Description: The first case was of a 66-year-old male patient who had presented with dizziness, headaches, gait disturbances, mild cognitive impairment, and visual field loss to the left side. MRI revealed 1 cerebellar and 2 occipital contrast-enhancing lesions that were suspicious for intracerebral metastases. The second case was of a 53-year-old male patient who had presented with temporal lobe epilepsy, anomic aphasia, and mild cognitive impairment. MRI demonstrated 4 contrast-enhancing lesions in the pons, temporal lobe, and thalamus that were suspicious for intracerebral lymphoma. Because of the radiological presentation, neoplastic disease was the most plausible diagnosis for both patients. However, repeated biopsies ruled out tumor manifestation, and the findings were finally consistent with CLIPPERS syndrome. The significant and long-lasting response to immunosuppressive treatment confirmed the diagnosis., Conclusions: In both cases, the characteristics of CLIPPERS syndrome imitated malignant tumor growth. This scenario can be challenging to clinicians and necessitates inclusion of this neuroinflammatory syndrome in the differential diagnosis of neuro-oncological disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite recent improvements in treatment of glioblastoma (GBM), some patients still have a short survival. We sought to develop a new risk score for preoperative assessment of short-term survival (STS) (<6 months) in patients with GBM., Methods: All adult patients who underwent surgical resection of GBM between 2004 and 2014 were included (N = 379). Demographic and clinical parameters, which were available at admission, were assessed. Variables were evaluated in univariate and multivariate analyses. The score was validated in a separate cohort of patients with GBM who underwent surgical resection between 2015 and 2018., Results: The following independent predictors of STS were integrated into a new score: body height (<169 cm, 1 point), arterial hypertension (1 point), age (≤54 years, 0 points; 55-74 years, 1 points; ≥75 years, 2 points), and poor clinical status (Karnofsky performance scale [KPS] score: ≤60%, 2 points; 70%-80%, 1 point; ≥90%, 0 points). The new risk score, SHORT (Small body height, Hypertension, Older age, Reduced KPS score, short-Term survival), ranged from 0 to 6 points and showed good accuracy of risk estimation for STS in GBM (area under the curve: 0.715). STS rates were 9.7%, 23.1%, and 70% in patients with GBM scoring <2 points, 2-4 points, and >4 points (P < 0.0001). The score was successfully validated (area under the curve: 0.770)., Conclusions: This study presents the SHORT score for preoperative assessment of STS risk in patients with GBM. This risk score needs external validation in larger patient cohorts from other institutions. Our score might be a tool to facilitate treatment decisions in patients with GBM before surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: There is an urgent need for more effective therapies for glioblastoma. Data from a previous unrandomised phase 2 trial suggested that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMT promoter. In the CeTeG/NOA-09 trial, we aimed to further investigate the effect of lomustine-temozolomide therapy in the setting of a randomised phase 3 trial., Methods: In this open-label, randomised, phase 3 trial, we enrolled patients from 17 German university hospitals who were aged 18-70 years, with newly diagnosed glioblastoma with methylated MGMT promoter, and a Karnofsky Performance Score of 70% and higher. Patients were randomly assigned (1:1) with a predefined SAS-generated randomisation list to standard temozolomide chemoradiotherapy (75 mg/m 2 per day concomitant to radiotherapy [59-60 Gy] followed by six courses of temozolomide 150-200 mg/m 2 per day on the first 5 days of the 4-week course) or to up to six courses of lomustine (100 mg/m 2 on day 1) plus temozolomide (100-200 mg/m 2 per day on days 2-6 of the 6-week course) in addition to radiotherapy (59-60 Gy). Because of the different schedules, patients and physicians were not masked to treatment groups. The primary endpoint was overall survival in the modified intention-to-treat population, comprising all randomly assigned patients who started their allocated chemotherapy. The prespecified test for overall survival differences was a log-rank test stratified for centre and recursive partitioning analysis class. The trial is registered with ClinicalTrials.gov, number NCT01149109., Findings: Between June 17, 2011, and April 8, 2014, 141 patients were randomly assigned to the treatment groups; 129 patients (63 in the temozolomide and 66 in the lomustine-temozolomide group) constituted the modified intention-to-treat population. Median overall survival was improved from 31·4 months (95% CI 27·7-47·1) with temozolomide to 48·1 months (32·6 months-not assessable) with lomustine-temozolomide (hazard ratio [HR] 0·60, 95% CI 0·35-1·03; p=0·0492 for log-rank analysis). A significant overall survival difference between groups was also found in a secondary analysis of the intention-to-treat population (n=141, HR 0·60, 95% CI 0·35-1·03; p=0·0432 for log-rank analysis). Adverse events of grade 3 or higher were observed in 32 (51%) of 63 patients in the temozolomide group and 39 (59%) of 66 patients in the lomustine-temozolomide group. There were no treatment-related deaths., Interpretation: Our results suggest that lomustine-temozolomide chemotherapy might improve survival compared with temozolomide standard therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. The findings should be interpreted with caution, owing to the small size of the trial., Funding: German Federal Ministry of Education and Research., (Copyright © 2019 Elsevier Ltd. All rights reserved.)