Glioblastoma in the oldest old: Clinical characteristics, therapy, and outcome in patients aged 80 years and older.

Background: Incidence rates of glioblastoma in very old patients are rising. The standard of care for this cohort is only partially defined and survival remains poor. The aims of this study were to reveal current practice of tumor-specific therapy and supportive care, and to identify predictors for survival in this cohort. Methods: Patients aged 80 years or older at the time of glioblastoma diagnosis were retrospectively identified in 6 clinical centers in Switzerland and France. Demographics, clinical parameters, and survival outcomes were annotated from patient charts. Cox proportional hazards modeling was performed to identify parameters associated with survival. Results: Of 107 patients, 45 were diagnosed by biopsy, 30 underwent subtotal resection, and 25 had gross total resection. In 7 patients, the extent of resection was not specified. Postoperatively, 34 patients did not receive further tumor-specific treatment. Twelve patients received radiotherapy with concomitant temozolomide, but only 2 patients had maintenance temozolomide therapy. Fourteen patients received temozolomide alone, 35 patients received radiotherapy alone, 1 patient received bevacizumab, and 1 took part in a clinical trial. Median progression-free survival (PFS) was 3.3 months and median overall survival (OS) was 4.2 months. Among patients who received any postoperative treatment, median PFS was 3.9 months and median OS was 7.2 months. Karnofsky performance status (KPS) ≥70%, gross total resection, and combination therapy were associated with better outcomes. The median time spent hospitalized was 30 days, accounting for 23% of the median OS. End-of-life care was mostly provided by nursing homes (n = 20; 32%) and palliative care wards (n = 16; 26%). Conclusions: In this cohort of very old patients diagnosed with glioblastoma, a large proportion was treated with best supportive care. Treatment beyond surgery and, in particular, combined modality treatment were associated with longer OS and may be considered for selected patients even at higher ages.

Symptom Burden in Glioblastoma: A Prospective Pilot Study from Diagnosis to First Progression.

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.

Fitness-to-drive for glioblastoma patients: Guidance from the Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM).

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).

Long-term apparent diffusion coefficient value changes in patients undergoing radiosurgical treatment of meningiomas.

PURPOSE: 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. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

MRI and 18FET-PET Predict Survival Benefit from Bevacizumab Plus Radiotherapy in Patients with Isocitrate Dehydrogenase Wild-type Glioblastoma: Results from the Randomized ARTE 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 contemporary perspective on the diagnosis and treatment of diffuse gliomas in adults.

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.

Impact of treatment decision algorithms on treatment costs in recurrent glioblastoma: a health economic study.

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.

Complementary and alternative medicine use by glioma patients in Switzerland.

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.

Spinal Metastases of Supratentorial Glioblastoma with Primitive Neuronal Component.

BACKGROUND: Glioblastoma multiforme with a primitive neuronal component is a rare entity, with few cases reported in the literature. CASE DESCRIPTION: A patient who had a supratentorial glioblastoma multiforme with a primitive neuronal component developed spinal metastasis during the disease course. With his history of leukemia during childhood, he was likely exposed to therapeutic ionizing brain radiation, which could have increased the risk of developing brain cancer in adulthood. CONCLUSIONS: The range of incidence rates of dissemination in the literature is 2%-4%, typically in cases of cerebellar glioblastoma multiforme, but as high as 25% in autopsy series. Our case highlights several other topics in the literature, such as immunohistochemical patterns that differ between the primary tumor and spinal metastases and dissemination locations, typically leptomeningeal or ventricular invasion.

Interictal epileptogenic zone localization in patients with focal epilepsy using electric source imaging and directed functional connectivity from low-density EEG.

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 < 0.05) concordance with the presumed EZ than patients with with ETLE. The brain volume accepted for concordance was significantly larger in TLE. SIGNIFICANCE: ESI and DFC derived from low-density EEG can reliably estimate the EZ from interictal spikes. Connectivity measures were not superior to ESI for EZ localization during interictal spikes, but the current validation of the localization of connectivity measure is promising for other applications.

Response assessment of meningioma: 1D, 2D, and volumetric criteria for treatment response and tumor progression.

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<0.01). Setting a volume change threshold above 40% did not correlate with survival. The interobserver agreement of 1D, 2D, and volume criteria is only moderate (kappa = 0.49, 0.46, 0.52, respectively). None of the criteria based on tumor size reduction were associated with OS (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.

Longitudinal Imaging of Tumor Volume, Diffusivity, and Perfusion After Preoperative Endovascular Embolization in Supratentorial Hemispheric Meningiomas.

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.

Epileptic Activity Increases Cerebral Amino Acid Transport Assessed by 18F-Fluoroethyl-l-Tyrosine Amino Acid PET: A Potential Brain Tumor Mimic.

O-(2-18F-fluoroethyl)-l-tyrosine (18F-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 18F-FET PET imaging is currently unknown. The aim of this retrospective analysis was to investigate the brain amino acid metabolism during epileptic seizures by 18F-FET PET and to elucidate the pathophysiologic background. METHODS: Ten patients with 11 episodes of serial seizures or status epilepticus, who underwent MRI and 18F-FET PET, were studied. The main diagnosis was glioma World Health Organization grade II-IV (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 18F-FET uptake, which was reversible in follow-up studies or negative shortly before and without any histologic or clinical signs of tumor recurrence. 18F-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 18F-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 18F-FET uptake pattern. Such periictal pseudoprogression represents a potential pitfall of 18F-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.

[Meningioma: management of the most common brain tumour]. / Das Meningeom: Management des häufigsten hirneigenen Tumors.

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.

Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas.

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.

Kinetics of tumor size and peritumoral brain edema before, during, and after systemic therapy in recurrent WHO grade II or III meningioma.

BACKGROUND: The efficacy of systemic antineoplastic therapy on recurrent World Health Organization (WHO) grades II and III meningiomas is unclear. METHODS: We performed a retrospective multicenter analysis of serial cranial MRI in patients with recurrent WHO II and III meningiomas treated with antineoplastic systemic therapies. Growth rates for tumor volume and diameter, as well as change rates for edema size, were calculated for all lesions. RESULTS: We identified a total of 34 patients (23 atypical, 11 anaplastic meningiomas) with a total of 57 meningioma lesions who had been treated at 6 European institutions. Systemic therapies included bevacizumab, cytotoxic chemotherapy, somatostatin analogues, and tyrosine kinase inhibitors. Overall, tumor growth rates decreased during systemic therapy by 51% for tumor diameter and 14% for tumor volume growth rates compared with the period before initiation of systemic therapy. The most pronounced decrease in meningioma growth rates during systemic therapy was evident in patients treated with bevacizumab, with a reduction of 80% in diameter and 59% in volume growth. Furthermore, a decrease in size of peritumoral edema after initiation of systemic therapy was exclusively observed in patients treated with bevacizumab (-107%). CONCLUSIONS: Our data indicate that systemic therapy may inhibit growth of recurrent WHO grades II and III meningiomas to some extent. In our small cohort, bevacizumab had the most pronounced inhibitory effect on tumor growth, as well as some anti-edematous activity. Prospective studies are needed to better define the role of medical therapies in this tumor type.

[Neurological complications in cancer patients]. / Neurologische Komplikationen bei onkologischen Patienten.

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.

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.

Clinical management and outcome of histologically verified adult brainstem gliomas in Switzerland: a retrospective analysis of 21 patients.

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.

Differentiation between calcification and hemorrhage in brain tumors using susceptibility-weighted imaging: a pilot study.

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.