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Purpose:To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma.Patients and Methods:Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm.Results:Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89–0.99] and for higher ADC (HR 0.18; CI, 0.05–0.66). Higher 18FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P = 0.09). High 18FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16–30.8).Conclusions:Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.

Note S1, Figure S1-S4, Table S1-S3

Introduction: The evaluation of symptom burden, performance status, and neurological function is still challenging in glioblastoma (GBM) patients. Patients may suffer from a wide spectrum of neurological symptoms like cognitive deficits, aphasia, or hemiparesis, which interfere to report to comprehensive questionnaires. However, an integrated and reliable neuro-oncological assessment is the key in the clinical management and in the evaluation of treatment benefits for GBM patients. Methods: We implemented an easy-to-use clinical toolkit for the prospective assessment and follow-up evaluation of GBM patients using the Karnofsky performance status (KPS), the National Institute of Health Stroke Scale (NIH-SS), and simple scores for the evaluation of key symptoms like fatigue, depression, and headache. Results: We prospectively followed 50 patients. The composite score (headache, depression, and fatigue), fatigue alone, the NIHSS, and the KPS were suitable biomarkers to evaluate symptom burden in GBM patients and indicate clinical disease progression. Discussion/Conclusion: The proposed clinical toolkit seems feasible in routine clinical practice and reflects changes in symptom burden in different stages of the postsurgical course of GBM patients in this monocentric clinical pilot trial.

Purpose: To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. Patients and Methods: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. Results: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89–0.99] and for higher ADC (HR 0.18; CI, 0.05–0.66). Higher 18FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P = 0.09). High 18FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16–30.8). Conclusions: Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.

A noninvasive method to predict the progress or treatment response of meningiomas is desirable to improve the tumor management. Studies showed that apparent diffusion coefficient (ADC) pretreatment values can predict treatment response in brain tumors. The aim of this study was to analyze changes of intratumoral ADC values in patients with meningiomas undergoing conservative or radiosurgery. MR images of 51 patients with diagnose of meningiomas were retrospectively reviewed. Twenty-five patients undergoing conservative or radiosurgery treatment, respectively, were included in the study. The follow-up data ranged between 1 and 10 years. Based on ROI analysis, the mean ADC values, ADC10%min, and ADC90%max were evaluated at different time points during follow-up. Baseline ADC values in between both groups were similar. The ADCmean values, ADC10%min, and ADC90%max within the different groups did not show any significant changes during the follow-up times in the untreated (ADCmean over 10 years period: 0.87 ± 0.05 × 10−3 mm2/s) and radiosurgically treated (ADCmean over 4 years period: 1.02 ± 0.12 × 10−3 mm2/s) group. However, statistically significant difference was observed when comparing the ADCmean and ADC90%max values of untreated with radiosurgically treated (p < 0.0001) meningiomas. Also, ADC10%min revealed statistically significant difference between the untreated and the radiosurgery group (p < 0.05). ADC values in conservatively managed meningiomas remain stable during the follow-up. However, meningiomas undergoing radiosurgery reveal significant change of the mean ADC values over time, suggesting that ADC may reflect a change in the biological behavior of the tumor. These observations might suggest the value of ADC changes as an indicator of treatment response.

Un patient de 73 ans se presente aux urgences initialement en raison «d’acces de faiblesse» recidivants et de signes presyncopaux. Il declare ne pas avoir ete victime de chutes.

Ein 73-jahriger Patient prasentierte sich initial aufgrund rezidivierender «Schwacheanfalle» und prasynkopaler Zustandsbilder auf der Notfallstation. Sturz­ereignisse wurden verneint.

OBJECTIVE The management of brain tumour patients who would like to resume driving is complex, and needs multidisciplinary input and a consensus among treating physicians. The Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM) aim to provide guidance on how to assess “fitness-to-drive” of glioblastoma patients and to harmonise the relevant procedures in Switzerland. METHODS At several meetings, Swiss neuro-oncologists discussed common practices on how to advise patients with a stable, i.e., non-progressive, glioblastoma, who wish to resume driving after the initial standard tumour treatment. All participants of the SwissNOS meetings were invited twice to return a questionnaire (modified Delphi process) on specific tools/procedures they commonly use to assess “fitness-to-drive” of their patients. Answers were analysed to formulate a tentative consensus for a structured and reasonable approach. RESULTS Consensus on minimum requirements for a “fitness-to-drive”programme for glioblastoma patients could be reached among Swiss neuro-oncologists. The recommendations were based on existing guidelines and expert opinions regarding patients with seizures, visual disturbances, cognitive impairment or focal deficits for safe driving. At this point in time, the Swiss neuro-oncologists agreed on the following requirements for glioblastoma patients after the initial standard therapy and without a seizure for at least 12 months: (1) stable cranial magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria, to be repeated every 3 months; (2) thorough medical history, including current or new medication, a comprehensive neurological examination at baseline (T0) and every 3 months thereafter, optionally an electrocencephalogram (EEG) at baseline; (3) ophthalmological examination including visual acuity and intact visual fields; and (4) optional neuropsychological assessment with a focus on safe driving. Test results have to be compatible with safe driving at any time-point. Patients should be informed about test results and optionally sign a document. CONCLUSIONS We propose regular thorough clinical neurological examination and brain MRI, optional EEG, neuropsychological and visual assessments to confirm “fitness-to-drive” for glioblastoma patients after initial tumour-directed therapy. The proposed “fitness-to-drive” assessments for glioblastoma patients serves as the basis for a prospective Swiss Pilot Project GLIODRIVE (BASEC ProjectID 2020-00365) to test feasibility, adherence and safety in a structured manner for patients who wish to resume driving. Research will focus on confirming the usefulness of the proposed tools in predicting “fitness-to-drive” and match results with events obtained from the road traffic registry (Strassenverkehrsamt).

Background and purpose Susceptibility-weighted magnetic resonance imaging (SWI) yields information regarding tumor biology (e.g., hemorrhage) of growing gliomas. SWI changes can also be observed as a consequence of treatment, for example radiation therapy. The aim of our study was to investigate how susceptibility changes occur during the time course after completion of standard treatment in newly diagnosed glioblastoma (GBM). Methods Eighteen GBM patients were retrospectively analyzed. After completion of therapy, imaging was performed every 3 months. MRI was analyzed at the following time points: after the third and sixth cycle of adjuvant temozolomide chemotherapy, thereafter in 3 month intervals and at recurrence. The number of SWI positive tumor pixels was quantified and compared with progression as defined by the RANO criteria on T2- and contrast-enhanced T1-weighted MRI sequences (T1-CE). Results The MRI interval between completion of the sixth chemotherapy cycle and last MRI before progression was 390 ± 292 days. Between the last MRI before progression and at progression a significant increase in SWI positive tumor pixels was observed (P = .012), whereas tumor size remained unchanged (RANO T2: P = .385; RANO T1-CE: P = .165). The number of SWI positive pixels remained unchanged between last MRI before progression until progression (P = .149), whereas RANO T2 and T1-CE showed tumor progression (interval 128 ± 69 days). Conclusions SWI positive pixel count increases significantly prior to changes in tumor size (RANO). Our findings may be explained by microbleeds compatible with stimulation of angiogenesis and possibly serve as an early biomarker of tumor progression.

Gliomas are intrinsic brain tumours, which are classified by the World Health Organization (WHO) into different grades of malignancy, with glioblastoma being the most frequent and most malignant subtype (WHO grade IV). Mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are frequent in lower (WHO II/III) grade tumours but typically absent in classical glioblastoma. IDH mutations are associated with a better prognosis compared with IDH wild-type tumours of the same WHO grade. Following detection of a tumour mass by imaging, maximum safe surgery as feasible is commonly performed to reduce mass effect and to obtain tissue allowing histopathological diagnosis and molecular assessment. Radiotherapy has been the mainstay in the treatment of diffuse gliomas for several decades. It provides improved local control, but is not curative. Furthermore, several randomised trials have shown that the addition of alkylating chemotherapy, either temozolomide or nitrosourea-based regimens, to radiotherapy results in prolonged survival. Tumour-treating fields (TTFields) have emerged as an additional treatment option in combination with maintenance temozolomide treatment for patients with newly diagnosed glioblastoma. Treatment at recurrence is less standardised and depends on the patient’s performance status, symptom burden and prior treatments. Bevacizumab prolongs progression-free survival in newly diagnosed and recurrent glioblastoma, but does not impact overall survival. However, in Switzerland and some other countries, it is still considered a valuable treatment option to reduce clinical symptom burden. Given the generally poor outcome for these patients, various novel treatment approaches are currently being explored within clinical trials including immunotherapeutic strategies such as immune checkpoint inhibition and the brain-penetrant proteasome inhibitor marizomib.

To explore a prognostic or predictive role of MRI and O-(2-Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in thisOverall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cmLarge pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent

AIMS Recurrent glioblastoma (GBM) is a disease with poor prognosis. Although several therapeutic approaches such as chemotherapy, irradiation or surgery have been investigated, there is no established standard therapy. A recent survey among Swiss neuro-oncology centres has shown considerable controversy in the treatment recommendations for any specific scenario of recurrent GBM. In view of the cost differences of the available treatment alternatives, the aim of our study was assess the financial impact of different institutional therapeutic strategies for recurrent GBM in Switzerland. METHODS We created a decision analytic model for each of the eight centres participating in the initial study with a centre-specific treatment algorithm to evaluate the average treatment cost per patient. The probability of decision criteria was varied by univariate and probabilistic sensitivity analysis over a wide range to account for the high level of uncertainty. Treatment costs were calculated from the perspective of the Swiss healthcare payer. RESULTS Mean treatment costs per patient calculated on the basis of the institutional treatment algorithms ranged from CHF 13,748 to CHF 22,072 depending on the probability of individual decision criteria. The most influential decision factors for the mean treatment costs were the probability of fit patients and the proportion of patients with resectable tumour recurrences. There was a significant correlation between the complexity of treatment algorithms in a centre and the resulting mean treatment costs. CONCLUSIONS Institutional treatment algorithms can be used to estimate the average treatment costs per patient, which are, however, highly sensitive to probability changes of individual decision criteria. Our study demonstrates a high variability in treatment costs for recurrent GBM among eight Swiss neuro-oncology centres based on individual institutional treatment algorithms.

Background The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT → TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population. Patients and methods ARTE was a 2 : 1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg×14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years. The primary objective was to obtain evidence for prolongation of median OS by the addition of bevacizumab to RT. Response was assessed by RANO criteria. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Exploratory studies included molecular subtyping by 450k whole methylome and gene expression analyses. Results Median PFS was longer in arm A than in arm B (7.6 and 4.8 months, P = 0.003), but OS was similar (12.1 and 12.2 months, P = 0.77). Clinical deterioration was delayed and more patients came off steroids in arm A. Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase (RTK) I methylation subtype (HR 0.25, P = 0.014) and proneural gene expression (HR 0.29, P = 0.025). In a Cox model of OS controlling for established prognostic factors, associations with more favorable outcome were identified for age

Background During the course of disease, most glioma patients learn that there is no cure for their tumor. It is therefore not uncommon for patients or caregivers to seek complementary and alternative medicine (CAM) treatments. Patterns of CAM use vary across the globe, but little is known about the type of, and motivation for, CAM use in most countries. Methods Here we conducted a cross-sectional survey of CAM use in patients harboring gliomas of World Health Organization (WHO) grades II to IV at 3 specialized neuro-oncology centers in Switzerland. Results Of 208 patients who returned the survey, approximately half reported having used or using CAM. CAM use was associated with younger age. Patients suffering from WHO grade II gliomas were less likely to indicate CAM use. The leading motivation for CAM use was to contribute actively to the treatment of the disease. CAM use was commonly not counseled or supervised by a health care professional. Cost and issues of reimbursement were not an important factor in the decision against or for CAM use. Conclusions Physicians caring for glioma patients should be aware of and explore CAM use to better understand patients’ attitudes toward their disease, to provide counseling, and to identify potential interactions of CAM with standard treatments for gliomas.

Zusammenfassung. Meningeome sind die häufigsten hirneigenen Tumoren und haben eine medizinische Relevanz in der Hausarztmedizin. Diese Tumoren sind überwiegend gutartig (WHO-Grad I) und können entweder beobachtet oder operiert werden. Bei einer kompletten Tumorentfernung ist das Rückfallrisiko gering. Höher-gradige Meningeome (WHO-Grad II/III) bedürfen meist einer multimodalen Therapie mit Operation und Strahlentherapie, auch wenn hierzu keine kontrollierten Studien vorliegen. Das Rezidivrisiko dieser Meningeome ist wesentlich höher, sodass engmaschiger mittels kranialer Magnetresonanztomografie nachuntersucht werden muss, um Rezidive früh zu entdecken. Neue Systemtherapien mit gezieltem Wirkmechanismus («targeted drugs») erweitern das therapeutische Spektrum und kommen zum Einsatz, wenn die lokalen Therapieverfahren versagen (z.B. Bevacizumab, Sunitinib). Bei Meningeomen aller WHO-Grade empfiehlt sich die Festlegung einer therapeutischen Strategie im Rahmen eines interdisziplinären Tumorboards.

2520 Background: Bevacizumab failed to demonstrate overall survival benefit despite markedly prolonged progression-free survival in glioblastoma patients. Reasons for this divergence may include suboptimal patient selection and delayed diagnosis of progression on MRI scans under bevacizumab. Imaging analyses of retrospective and uncontrolled clinical trial cohorts suggest MRI diffusion mapping as a predictor of benefit from bevacizumab. Moreover, amino acid PET has been proposed by the RANO working group for the differentiation of tumor versus edema or gliosis based on proof-of-principle studies demonstrating earlier detection of progression with PET compared to MRI. Methods: ARTE (NCT01443676) was a 2:1 randomized, multi-center, open-label trial of hypofractionated radiotherapy in combination with intravenous bevacizumab every 2 weeks (BEV/RT) versus RT alone in patients with newly diagnosed glioblastoma aged 65 years or older. Patients with histologically and molecularly confirmed IDH wildtype glioblastoma aged 65 years or older were analyzed. MRI was available from 67 and serial 18FET PET from 30 patients in this post hoc analysis. 18FET PET intensity ratios and herein reported MRI parameters including tumor volumetric analyses and ADC were analyzed blinded for outcome and study arm. Results: Demographic, clinical and molecular parameters were balanced between treatment arms. Overall survival benefit from bevacizumab was observed for larger contrast-enhancing tumor volumes (hazard ratio [HR] per cm3 0.94, 95% CI 0.89-0.99, p = 0.032) and higher ADC (HR 0.18, 95% CI 0.05-0.66, p = 0.025) on pre-treatment MRI. Response in the BEV/RT arm by the standard MRI-based RANO criteria was associated with overall survival by trend (HR 0.56, 95% CI 0.30-1.10, time-dependent p = 0.094). In a multivariate model controlling for established risk factors, 18FET tumor-to-brain uptake ratios (TBR) of non-contrast-enhancing tumor portions predicted inferior overall survival specifically in the BEV/RT arm (HR [per 0.1 18FET TBR] 1.50, 95% CI 1.05-2.13, time-dependent p = 0.025). Controlling for 18FET TBR at first follow-up identified benefit from BEV/RT by trend (HR 0.41, 95% CI 0.16-1.07, p = 0.069). Conclusions: Large contrast-enhancing tumor mass and high ADC identify patients with overall survival benefit from bevacizumab. Under bevacizumab, non-contrast enhancing tumor portions can be adequately monitored by amino acid PET.

BACKGROUND: Patients suffering from brain tumors, as other cancer patients, may rely on additional support of complementary and alternative medicine (CAM) treatment during the course of disease. However, the assessment and documentation of CAM is not necessarily part of the clinical routine in oncological consultations. Moreover, CAM comprises different agents and treatments that may vary depending on the country the patient lives. Overall, there is a lack of information on type and motivation for CAM use in glioma patients in Switzerland. MATERIAL AND METHODS: A multi-center cross-sectional survey analysis of CAM use in glioma patients was conducted in 3 specialized Neuro-Oncology Centers in Switzerland from 2012–2015. On the occasion of a regular consultation, a questionnaire including multiple choice questions as well as open response questions was provided to patients suffering from a glioma WHO II-IV. RESULTS: Overall, 208 patients completed the survey. Approximately half of the patients (n=101 patients, 49 %) reported the use of CAM during the course of the disease. Patients reported the wish to contribute actively to the cancer treatment as the most important motivation for CAM use. CAM user were most likely younger patients, usually using CAM without medical supervision and without necessarily being reimbursed by the insurance company. CAM use was distributed amongst WHO grades and both genders. CONCLUSIONS: In this multi-center survey analysis conducted in Switzerland, almost half of the glioma patients reported to have used CAM during the course of the disease. This demand should be addressed by the treating physicians. An accurate documentation and counseling could improve patient care, by avoiding potential interactions with the standard treatment and by incorporation of patients’ needs into therapy. Funded by the Swiss Brain Tumor Foundation

Summary Objective Electrical source imaging (ESI) is used increasingly to estimate the epileptogenic zone (EZ) in patients with epilepsy. Directed functional connectivity (DFC) coupled to ESI helps to better characterize epileptic networks, but studies on interictal activity have relied on high‐density recordings. We investigated the accuracy of ESI and DFC for localizing the EZ, based on low‐density clinical electroencephalography (EEG). Methods We selected patients with the following: (a) focal epilepsy, (b) interictal spikes on standard EEG, (c) either a focal structural lesion concordant with the electroclinical semiology or good postoperative outcome. In 34 patients (20 temporal lobe epilepsy [TLE], 14 extra‐TLE [ETLE]), we marked interictal spikes and estimated the cortical activity during each spike in 82 cortical regions using a patient‐specific head model and distributed linear inverse solution. DFC between brain regions was computed using Granger‐causal modeling followed by network topologic measures. The concordance with the presumed EZ at the sublobar level was computed using the epileptogenic lesion or the resected area in postoperative seizure‐free patients. Results ESI, summed outflow, and efficiency were concordant with the presumed EZ in 76% of the patients, whereas the clustering coefficient and betweenness centrality were concordant in 70% of patients. There was no significant difference between ESI and connectivity measures. In all measures, patients with TLE had a significantly higher (P

International audience; Background: Meningiomas are the most common primary brain tumors in adults. Due to their variable growth rates and irregular tumor shapes, response assessment in clinical trials remains challenging and no standard criteria have been defined. We evaluated 1D, 2D, and volume imaging criteria to assess whether a volumetric approach might be a superior surrogate for overall survival (OS).Methods: In this retrospective multicenter study, we evaluated the clinical and imaging data of 93 patients with recurrent meningiomas treated with pharmacotherapy. One-dimensional (1D), 2D, and volumetric measurements of enhancing tumor on pre- and post-treatment MRI were compared at 6 and 12 months after treatment initiation. Cox proportional hazards models were used to examine the relationship between each imaging criterion and OS.Results: The median age of the patient cohort is 51 years (range 12-88), with 14 World Health Organization (WHO) grade I, 53 WHO grade II, and 26 WHO grade III meningiomas. Volumetric increase of 40% and unidimensional increase by 10 mm at 6 months and 12 months provided the strongest association with overall survival (HR = 2.58 and 3.24 respectively, p 0.09).Conclusion: Compared with 1D (Response Evaluation Criteria In Solid Tumors 1.1) and 2D (Response Assessment in Neuro-Oncology) approaches, volumetric criteria for tumor progression has a stronger association with OS, although the differences were only modest. The interobserver variability is moderate for all 3 methods. Further validation of these findings in an independent patient cohort is needed.

Hemorrhage is common in brain tumors. Due to characteristic magnetic field changes induced by hemosiderin it can be detected using susceptibility weighted MRI (SWI). Its relevance to clinical syndromes is unclear. Here we investigated the patterns of intra-tumoral SWI positivity (SWI(pos)) as a surrogate for hemosiderin with regard to the prevalence of epilepsy. We report on 105 patients with newly diagnosed supra-tentorial gliomas and brain metastasis. The following parameters were recorded from pre-operative MRI: (1) SWI(pos) defined as dot-like or fine linear signal changes; (2) allocation of SWI(pos) to tumor compartments (contrast enhancement, central hypointensity, non-enhancing area outside contrast-enhancement); (3) allocation of SWI(pos) to include the cortex, or SWI(pos) in subcortical tumor parts only; (4) tumor size on T2 weighted and gadolinium-enhanced T1 images. 80 tumors (76 %) showed SWI(pos) (4/14 diffuse astrocytoma WHO II, 5/9 anaplastic astrocytoma WHO III, 41/46 glioblastoma WHO IV, 30/36 metastasis). The presence of SWI(pos) depended on tumor size but not on patient's age, medication with antiplatelet drugs or anticoagulation. Seizures occurred in 60 % of patients. Cortical SWI(pos) significantly correlated with seizures in brain metastasis (p = 0.044), and as a trend in glioblastoma (p = 0.062). Cortical SWI(pos) may confer a risk for seizures in patients with newly diagnosed brain metastasis and glioblastoma. Whether development of cortical SWI(pos) induced by treatment or by the natural course of tumors also leads to the new onset of seizures has to be addressed in longitudinal studies in larger patient cohorts.

Objective To describe longitudinal image changes in supratentorial hemispheric meningiomas based on magnetic resonance imaging after preoperative embolization using calibrated microspheres. Methods A total of 14 patients with symptomatic supratentorial meningiomas were included in a prospective, mono-centric, mono-arm study. Magnetic resonance imaging changes on diffusion-weighted imaging, dynamic contrast susceptibility–perfusion-weighted imaging, susceptibility-weighted imaging, and magnetization-prepared rapid acquisition gradient-echo sequence T1-weighted postcontrast sequences 6 and 48 hours after embolization were evaluated and correlated with angiographic and clinical data. Results The mean age of the patients was 63 ± 12.7 years with an equal female/male ratio. Twelve meningiomas were World Health Organization grade I and II tumors. After embolization, baseline apparent diffusion coefficient (901 ± 166 mm2/s) decreased significantly within 6 hours (696 ± 115 mm2/s, P = 0.0008) as well within 48 hours (752 ± 134 mm2/s; P = 0.0147). Baseline mean ratio of relative cerebral blood volume (rCBV)tumor/rCBVwhite matter (3.67 ± 1.83) and relative cerebral blood flow (rCBF)tumor/rCBFwhite matter (2.89 ± 1.57) significantly decreased after embolization within 6 hours (rCBVtumor/rCBVwhite matter of 1.45 ± 0.9; P = 0.0007, rCBF of 1.16 ± 0.68; P = 0.0029) and 48 hours (rCBV of 1.50 ± 1.07; P = 0.0009, rCBFtumor/rCBFwhite matter of 1.19 ± 0.8; P = 0.003). The viable enhanced baseline mean tumor volume (54.3 ± 34.9 mm3) was sustainably and significantly diminished within 6 hours (26.6 ± 20.8 mm3; P = 0.02) and 48 hours (29.7 ± 22.5 mm3; P = 0.035) after embolization. There was a good correlation between angiographic devascularization rate and the embolized tumor volume at 6 hours (r = 0.7; P = 0.03) and 48 hours (r = 0.78; P = 0.041). Conclusions Preoperative meningioma embolization with calibrated microspheres is safe and effectively induces a significant and sustainable tissue transformation over 48 hours.

The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT→TMZ) prolonged progression-free survival (PFS), but not overall survival (OS) in patients with newly diagnosed glioblastoma in two double-blind phase III trials. Elderly and frail patients are underrepresented in most clinical trials, but early reports of bevacizumab in glioblastoma suggested preferential benefit in this population. ARTE was a 2:1 randomized, multi-center, open-label trial of hypofractionated RT (40 Gy in 15 fractions) in combination with bevacizumab (10 mg/kg x 14 days) (arm A, N=50) versus RT alone (arm B, N=25) in patients with newly diagnosed glioblastoma aged >65 years. The primary endpoint was median OS. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Response was assessed by RANO criteria. Exploratory studies included 18F-fluoro-ethyltyrosine positron emission tomography (FET-PET, N=34), as well as whole methylome (N=57) and nanostring gene expression (N=54) analyses. Median PFS was longer in arm A versus arm B (7.6 vs. 4.8 months, p=0.003), but OS was similar (12.1 vs 12.2 months, p=0.8). Clinical deterioration was delayed and more patients came off steroids in arm A versus arm B. Longer PFS in arm A versus arm B was confined to the receptor tyrosine kinase (RTK) I methylation subtype and to the proneural gene expression subtype, but was not observed for patients with RTK II, classical or mesenchymal subtype glioblastoma. Applying a Cox model to OS that controlled for established prognostic factors, we detected an association with age and KPS. Exploration of imaging predictors of OS in this model identified the presence of non-enhancing tumor detected by FET-PET (HR 0.31, p=0.02) as an important prognostic factor. Efficacy outcomes and exploratory analyses of ARTE do not support the notion that bevacizumab generally prolongs survival in elderly glioblastoma patients. However, novel molecular and imaging biomarkers may identify patients with preferential benefit from bevacizumab.

Positron emission tomography (PET) with radiolabelled amino acids provides information on the behaviour of gliomas with and without blood–brain barrier (BBB) disruption. This is of importance in several clinical conditions and significantly complements findings which remain unresolved by standard MRI alone. In low-grade gliomas, amino acid PET allows early response assessment during chemotherapy which can be used to individually tailor chemotherapy duration. In high-grade gliomas, it enables the differentiation of treatment-related changes from tumor progression during cytotoxic therapy, and to identify treatment failure early during anti-angiogenic therapies. Previous studies indicate that these informations have impact on cost-effectiveness. As most of the current data are obtained from smaller retrospective studies, prospective validation is required.

Introduction: The prognosis of glioblastoma (GBM) has been improved by new surgical techniques, optimized radiation and systemic therapy regimen. It becomes all the more important to define surrogate markers for assessment of treatment response and tumor progression. Response Assessment in Neurooncology (RANO) criteria in GBM rely on the measurement of perpendicular tumor diameters on contrast-enhanced T1-MRI. Microbleeds represent a hallmark of GBM and can be detected by ­susceptibility-weighted MRI (SWI-MRI). The limitations of the RANO criteria led us to investigate whether SWI-MRI can be used to assist in early detection of GBM progression. Materials and Methods: We retrospectively analysed patients with newly diagnosed GBM treated with surgery, concomitant radiation therapy with temozolomide-chemotherapy (TMZ-CT) and adjuvant TMZ-CT. We included only patients who remained stable after completion of the 6 cycles of adjuvant TMZ-CT but progressed thereafter. MRI scans of 5 different points in time were analysed: pre-operatively, after the 3rd and 6th cycle of TMZ-CT, last MRI before progression and at progression (RANO). The number of SWI positive tumor pixels was measured by region-of-interest analysis, and was compared between the different time points and with contrast-enhanced T1-MRI. Results: 18 patients were enrolled. The progress of SWI positivity during the course of the disease of each patient was analysed. Statistical analysis demonstrated no significant change between the 3rd and 6th TMZ-CT cycle. However, we found a significant difference (p

OBJECTIVE. Our aim was to develop a robust method to differentiate calcification from hemorrhage in gliomas. Histopathologic examination was performed to validate hemorrhage and calcification. CONCLUSION. Phase images from eleven patients with glioma yielded statistically significant phase-shift values for calcification and hemorrhage compared with normal brain, whereas CT showed substantial overlap of Hounsfield units. Phase image analysis correctly differentiated between intratumoral calcification and hemorrhage in 86% of cases.

Low-grade gliomas (LGGs) may harbor malignant foci, which are characterized by increased tumor cellularity and angiogenesis. We used diffusion-weighted MR imaging (apparent diffusion coefficient [ADC]) and PET with the amino acid O-(2-(18)F-fluorethyl)-L-tyrosine ((18)F-FET) to search for focal changes of diffusion (ADC) and amino acid uptake and to investigate whether focal changes in these parameters colocalize within LGGs.We retrospectively selected 18 patients with nonenhancing LGG. All patients had undergone (18)F-FET PET and MR imaging for preoperative evaluation or for therapy monitoring in recurrent or progressive LGG. Region-of-interest analysis was performed to compare (18)F-FET uptake and ADC values in areas with focal intratumoral maximum metabolic activity and diffusion restriction and between tumor and normal brain. (18)F-FET uptake was normalized to the mean cerebellar uptake (ratio). ADC values were also compared with the (18)F-FET uptake on a voxel-by-voxel basis across the whole tumor.The mean focal maximum (mean ± SD, 1.69 ± 0.85) and global (18)F-FET uptake in tumors (1.14 ± 0.41) exceeded that of normal cortex (0.85 ± 0.09) and cerebrospinal fluid (0.82 ± 0.20). ADC values in the area with most restricted diffusion (1.07 ± 0.22 × 10(-3) mm(2)/s) and in the whole tumor (1.38 ± 0.27 × 10(-3) mm(2)/s) were in the range between normal cortex (0.73 ± 0.06 × 10(-3) mm(2)/s) and cerebrospinal fluid (2.84 ± 0.09 × 10(-3) mm(2)/s). (18)F-FET uptake did not correlate with corresponding (colocalizing) ADC values, either in the area with focal maximum metabolic activity or in the area with most restricted diffusion or in the whole tumor.There is no congruency between (18)F-FET uptake and diffusivity in nonenhancing LGG. Diffusion restriction in these tumors most likely represents changes in brain and tumor cell densities as well as alteration of water distribution and is probably not directly correlated with the density of tumor cells.

Meningiomas are the most common primary brain tumours in adults and are therefore relevant for general practitioners. Most meningiomas are benign and neurosurgical resection offers the best chance of cure. However, complete resection is not achievable in many patients. This accounts for a relevant rate of tumour recurrences within 15 years of follow up. In atypical and anaplastic meningiomas of WHO grade II and III time to recurrence is dramatically shorter and these tumours need multimodal treatment strategies including postoperative radiotherapy. Various systemic treatments have occasionally been used as salvage therapy, but were essentially not effective. Only recently, Sunitinib, a small thyrosine kinase inhibitor as well as bevacizumab, a therapeutic antibody, have shown more promising results in highly pretreated, refractory meningioma patients.

O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) PET is a well-established method increasingly used for diagnosis, treatment planning, and monitoring in gliomas. Epileptic activity, frequently occurring in glioma patients, can influence MRI findings. Whether seizures also affect F-18-FET PET imaging is currently unknown. The aim of this retrospective analysis was to investigate the brain amino acid metabolism during epileptic seizures by F-18-FET PET and to elucidate the pathophysiologic background. Methods: Ten patients with 11 episodes of serial seizures or status epilepticus, who underwent MRI and F-18-FET PET, were studied. The main diagnosis was glioma World Health Organization grade II-1V (n = 8); 2 patients suffered from nonneoplastic diseases. Immunohistochemical assessment of LAT1/ LAT2/CD98 amino acid transporters was performed in seizure-affected cortex (n = 2) and compared with glioma tissues (n = 3). Results: All patients exhibited increased seizure-associated strict gyral F-18-FET uptake, which was reversible in follow-up studies or negative shortly before and without any histologic or clinical signs of tumor recurrence. F-18-FET uptake corresponded to structural MRI changes, compatible with cortical vasogenic and cytotoxic edema, partial contrast enhancement, and hyperperfusion. Patients with prolonged postictal symptoms lasting up to 8 wk displayed intensive and widespread 1 lobe) cortical F-18-FET uptake. LAT1/LAT2/CD98 was strongly expressed in neurons and endothelium of seizure-affected brains and less in reactive astrocytosis. Conclusion: Seizure activity, in particular status epilepticus, increases cerebral amino acid transport with a strict gyral F-18-FET uptake pattern. Such periictal pseudoprogression represents a potential pitfall of F-18-FET PET and may mimic brain tumor. Our data also indicate a seizure-induced upregulation of neuronal, endothelial, and less astroglial LAT1/LAT2/CD98 amino acid transporter expression.

Background Patients with WHO grade II glioma may respond to chemotherapy that is currently not standardized regarding timing and treatment duration. Metabolic changes during chemotherapy may precede structural tumor volume reductions. We therefore compared time courses of amino acid PET and MRI responses to temozolomide (TMZ) and assessed whether responses correlated with seizure control and progression-free survival (PFS). Methods PET and MRI were performed before and during TMZ chemotherapy. Tumor volumes were calculated using regions-of-interest analysis. Amino acid uptake was also quantified as metabolically active tumor volume and tumor-to-cerebellum uptake ratio. Results One hundred twenty-five PET and 125 MRI scans from 33 patients were analyzed. Twenty-five patients showed metabolic responses that exhibited an exponential time course with a 25% reduction of the active volume on average after 2.3 months. MRI responses followed a linear course with a 25% reduction after 16.8 months. Reduction of metabolically active tumor volumes, but not reduction of PET uptake ratios or MRI tumor volumes, correlated with improved seizure control following chemotherapy (P = .012). Receiver-operating-characteristic curve analysis showed that a decrease of the active tumor volume of ≥80.5% predicts a PFS of ≥60 months (P = .018) and a decrease of ≥64.5% a PFS of ≥48 months (P = .037). Conclusions Amino acid PET is superior to MRI for evaluating TMZ responses in WHO grade II glioma patients. The response delay between both imaging modalities favors amino acid PET for individually tailoring the duration of chemotherapy. Additional studies should investigate whether this personalized approach is appropriate with regard to outcome.

Despite moderate improvements in outcome of glioblastoma after first-line treatment with chemoradiation recent clinical trials failed to improve the prognosis of recurrent glioblastoma. In the absence of a standard of care we aimed to investigate institutional treatment strategies to identify similarities and differences in the pattern of care for recurrent glioblastoma. We investigated re-treatment criteria and therapeutic pathways for recurrent glioblastoma of eight neuro-oncology centres in Switzerland having an established multidisciplinary tumour-board conference. Decision algorithms, differences and consensus were analysed using the objective consensus methodology. A total of 16 different treatment recommendations were identified based on combinations of eight different decision criteria. The set of criteria implemented as well as the set of treatments offered was different in each centre. For specific situations, up to 6 different treatment recommendations were provided by the eight centres. The only wide-range consensus identified was to offer best supportive care to unfit patients. A majority recommendation was identified for non-operable large early recurrence with unmethylated MGMT promoter status in the fit patients: here bevacizumab was offered. In fit patients with late recurrent non-operable MGMT promoter methylated glioblastoma temozolomide was recommended by most. No other majority recommendations were present. In the absence of strong evidence we identified few consensus recommendations in the treatment of recurrent glioblastoma. This contrasts the limited availability of single drugs and treatment modalities. Clinical situations of greatest heterogeneity may be suitable to be addressed in clinical trials and second opinion referrals are likely to yield diverging recommendations.

BACKGROUND: Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult brainstem gliomas. METHODS: A retrospective chart review of adults (> age 18 years) was conducted. Brainstem glioma was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. RESULTS: 21 patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 versus 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (3 in each group), radiochemotherapy (2 versus 6), chemotherapy alone (0 versus 2) or no postoperative therapy (3 versus 1). Median PFS (24.1 versus 5.8 months; log-rank, p = 0.009) and mOS (30.5 versus 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. CONCLUSIONS: Histologically verification of adult brainstem glioma is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.

Purpose Positron emission tomography (PET) with radiolabeled amino acids provides information on biopsy target and chemotherapy response in patients with low-grade gliomas (LGG). In this article, we addressed whether PET with F-18 choline (CHO) detects increased metabolism in F-18 fluoroethyltyrosine (FET)-negative LGG patients. Methods Six LGG patients with nongadolinium-enhancing (magnetic resonance) FET-negative LGG were imaged with CHO PET. Regions of interest were positioned over tumor and contralateral brain. Uptake of FET and CHO was quantified as count ratio of tumor to contralateral brain. Results The mean FET uptake ratio for FET-negative LGG was 0.95 ± 0.03 (mean ± standard deviation). Five tumors did not show increased uptake ratios for CHO (0.96 ± 0.12). Slightly increased CHO uptake was found in 1 patient (1.24), which, however, was not associated with tumor visualization. Conclusions Amino acid and choline uptake appear to behave similar in nongadolinium-enhancing LGG. For clinical purposes, CHO PET is not superior to FET PET.

2014 Background: The addition of bevacizumab (BEV) to first-line temozolomide chemoradiotherapy prolonged progression-free survival (PFS), but not overall survival (OS) in newly diagnosed glioblastoma in two phase III trials. Elderly and frail patients are underrepresented in most clinical trials, but early uncontrolled reports of BEV treatment of glioblastoma suggested preferential benefit in this patient population. Methods: ARTE was a 2:1 randomized, multi-center, open-label trial of hypofractionated radiotherapy (RT) in combination with intravenous BEV every 2 weeks (Arm A, N = 50) versus RT alone (Arm B, N = 25) in patients with newly diagnosed glioblastoma aged 65 years or older. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Response was assessed using Response Assessment in Neuro-Oncology (RANO) criteria. Exploratory imaging studies included apparent diffusion coefficient (ADC) mapping and 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET). Results: Established prognostic factors including age, Karnofsky performance score (KPS), O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation and steroid intake at study entry were balanced between arms. Median PFS was longer in Arm A vs. Arm B (7.6 vs. 4.8 months, p = 0.003), but OS was similar (12.1 vs 12.2 months, p = 0.8). Prior to progression, no differences in QoL were noted, but clinical deterioration was deferred in Arm A vs. Arm B. In a Cox model that controlled for established prognostic factors, an association with prolonged PFS was detected for Arm A versus Arm B (hazard ratio [HR] 0.36, p = 0.001) and for KPS 90-100% versus 60-80% (HR 0.50, p = 0.02). Applying a similar Cox model to OS detected an association with age 65-69 vs 70+ (HR 0.52, p = 0.02) and KPS 90-100% versus 60-80% (HR 0.53, p = 0.03). Exploration of imaging predictors of OS for Arm A identified response by RANO (HR 0.52, p = 0.02), but detected no prognostic role for T2, ADC or FET signal intensity. Conclusions: Efficacy outcomes and exploratory imaging analyses of the ARTE trial do not support the notion that benefit from BEV is more pronounced in elderly glioblastoma patients. Clinical trial information: NCT01443676.

Introduction: Meningiomas may be highly vascularized and therefore respond to antiangiogenic treatment such as bevacizumab (Bev). Here we report on the time course of diffusivity as surrogate of tumor cell density and ischemic tissue changes in a patient with multiple intra- and extracranial meningiomas WHO grade III. Tumors initially responded to Bev, but were refractory at second Bev exposure. Materials and Methods: A 73 years old patient was studied at the time of 7th tumor recurrence. Size and diffusivity (apparent diffusion coefficient, ADC) of six meningiomas were quantified using ROI analysis on gadolinium-enhanced T1-weighted and corresponding diffusion weighted MRI. Bev treatment was delivered every two weeks with a dose of 10 mg/kg per infusion. Results: Mean tumor size increased 3.5-fold during spontaneous growth over 3.5 months, which was paralleled by an ADC decrease from 750 ± 214 to 644 ± 83*10-6mm2/s (mean±SD). The first Bev treatment period led to a response of all six meningiomas and induced a peak tumor size decrease of 70% at seven months. During that period ADC values increased 1.4-fold reaching a maximum already at 2 months. After seven months Bev had to be discontinued due to limb edema and proteinuria. Without Bev tumor size again increased 2.7-fold over seven months. Therefore Bev treatment was resumed, however, during the second treatment period of 4 months tumor size further increased, but ADC values remained unchanged (mean 1030 ± 321*10-6mm2/s). DISCUSSION: Successful Bev exposure lead to an early ADC increase which may be attributed to ischemic tumor damage and a decrease of tumor cell density. Vice versa, ADC remained unchanged during Bev resistence which indicates that ADC measurement may predict antiangiogenic treatment response or failure. This issue has to be addressed in a larger study. If confirmed ADC may be used to individualize meningioma treatment with Bev.

BACKGROUND: Two phase III trials of bevacizumab (BEV) in newly diagnosed glioblastoma demonstrated prolonged progression-free survival (PFS), but failed to prolong overall survival (OS). Retrospective reports and early phase trials of bevacizumab in glioblastoma patients emphasized that benefit was preferentially seen in frail or elderly patients, but such patients are underrepresented in most clinical trials. Here, we report the outcome of an elderly population with newly diagnosed glioblastoma randomized to receive hypofractionated radiotherapy alone or in combination with bevacizumab. METHODS: ARTE (NCT01443676) is a 2-arm, 2:1 randomized, parallel group, explorative, open-label trial of hypofractionated radiotherapy (RT) (15 x 2.66 Gy = 40 Gy) in combination with intravenous BEV every two weeks until progression (BEV+RT) versus RT alone. Major inclusion criteria included age 65 years or older, newly diagnosed glioblastoma, and Karnofsky performance score of 60 or more. An amendment (11/2013) requested demonstrating the absence of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation when it became clear that MGMT promoter methylation predicted larger benefit from temozolomide alone than from radiotherapy alone in patients with glioblastoma aged 65 years or older. Cognitive functioning was monitored by Mini Mental Status Examination and quality of life by utilizing the EORTC QLQ-C30/BN20 modules. Cox proportional hazard models were applied to obtain prognostic factors. Results: Of 75 randomized patients, 50 received BEV+RT and 25 received RT alone. Isocitrate dehydrogenase (IDH)-1 mutation status was uniformly wildtype in all 41 patients with available documentation and MGMT was unmethylated in 55 (76%) of 72 patients with MGMT testing. Established prognostic factors were balanced between both treatment arms, including age, MGMT promoter methylation, Karnofsky performance score, or steroid intake at randomization. Common Terminology Criteria for Adverse Events grade 3 or 4 toxicity was infrequent in both treatment arms. Prior to progression, no differences in cognitive functioning or quality of life were noted between treatment arms. BEV+RT was superior to RT alone for median PFS (7.6 months [95% CI 6.2–9.0] vs. 4.8 months [95% CI 3.0–6.6], P=0.003), but not OS (12.1 months [95% CI 10.2–14.0] vs 12.2 months [95% CI 9.2–15.2], P=0.77). In a Cox model controlling for established prognostic factors to determine predictors of inferior PFS, an association with outcome was detected for BEV+RT versus RT (HR 0.36 [95% CI 0.20–0.65], p=0.001) and for KPS 90–100% versus 60–80% (HR 0.50 [95% CI 0.28–0.89], p=0.018). CONCLUSION: The results of the randomized ARTE trial fail to support the notion that the addition of BEV improves outcome specifically in elderly patients with glioblastomas without MGMT promoter methylation.

Neurological symptoms in cancer patients have a great impact on quality of life and need an interdisciplinary approach. They lead to significant impairment in activities of daily living (gait disorders, dizziness), a loss of patients independency (vegetative disturbances, wheel-chair dependency) and interfere with social activities (ban of driving in case of epilepsy). In this article we describe three main and serious neurological problems in the context of oncological patients. These are chemotherapy-induced polyneuropathy, malignant spinal cord compression and epileptic seizures. Our aim is to increase the awareness of neurological complications in cancer patients to improve patients care.Neurologische Symptome und Komplikationen bei Patienten mit einer onkologischen Erkrankung sind in vielerlei Hinsicht für die interdisziplinäre Betreuung von Bedeutung. Nicht selten führen sie zu einer erheblichen Behinderung in den Alltagsfähigkeiten (Gangstörungen, Schwindel), zu einem Verlust der Patientenautonomie (Blasen-Mastdarmstörungen, Rollstuhlpflichtigkeit) und zu einer Störung des Sozial- und Arbeitslebens (Verlust der Fahreignung bei Epilepsie). In diesem Artikel stellen wir drei klinisch relevante neurologische Komplikationen im Kontext onkologischer Erkrankungen vor. Dieses sind die Chemotherapie-induzierte Polyneuropathie, spinale Kompressionen und epileptische Anfälle. Der vorliegende Übersichtsartikel zielt darauf ab, das Wissen um neurologische Komplikationen bei Krebspatienten zu vertiefen, Komplikationen vorzubeugen, um die Patientenversorgung weiter zu verbessern.Les symptômes neurologiques chez les malades cancéreux ont un grand impact sur la qualité de vie et requièrent une approche multidisciplinaire. Ces symptômes entravent significativement les activités de tous les jours (troubes de la marche, sensations vertigineuses), une perte de l'indépendance (troubles végétatifs, dépendance d'une chaise roulante) et interfèrent avec les activités sociales (conduite d'un véhicule interdite en cas d'épilepsie). Dans cet article seront décrits trois problèmes neurologiques importants et graves rencontrés chez les malades oncologiques. Il s'agit de la polyneuropathie induite par la chimiothérapie, la compression de la moelle épinière par des lésions cancéreuses et les crises épileptiques. Le but est d'améliorer les connaissances des complications neurologiques du cancer et par ce biais la qualité de la prise en charge des malades cancéreux.

Neurologische Symptome und Komplikationen bei Patienten mit einer onkologischen Erkrankung sind in vielerlei Hinsicht für die interdisziplinäre Betreuung von Bedeutung. Nicht selten führen sie zu einer erheblichen Behinderung in den Alltagsfähigkeiten (Gangstörungen, Schwindel), zu einem Verlust der Patientenautonomie (Blasen-Mastdarmstörungen, Rollstuhlpflichtigkeit) und zu einer Störung des Sozial- und Arbeitslebens (Verlust der Fahreignung bei Epilepsie). In diesem Artikel stellen wir drei klinisch relevante neurologische Komplikationen im Kontext onkologischer Erkrankungen vor. Dieses sind die Chemotherapie-induzierte Polyneuropathie, spinale Kompressionen und epileptische Anfälle. Der vorliegende Übersichtsartikel zielt darauf ab, das Wissen um neurologische Komplikationen bei Krebspatienten zu vertiefen, Komplikationen vorzubeugen, um die Patientenversorgung weiter zu verbessern.

Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas (BSGs) remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult BSGs. A retrospective chart review of adults (age >18 years) was conducted. BSG was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. Twenty one patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 vs. 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (three in each group), radiochemotherapy (2 vs. 6), chemotherapy alone (0 vs. 2) or no postoperative therapy (3 vs. 1). Median PFS (24.1 vs. 5.8 months; log-rank, p = 0.009) and mOS (30.5 vs. 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. Histologically verification of adult BSGs is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.

Meningiomas represent the most common primary brain tumor and comprise 3 World Health Organization (WHO) grades, the most frequent being WHO grade I (90 %). Surgery is mandatory to establish the diagnosis and to remove the tumor; however, complete resection can be achieved in only