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Background: Glioblastoma is the most common malignant primary brain tumour in adults and driven by various genomic alterations. Next generation sequencing (NGS) provides timely information about the genetic landscape of tumours and might detect targetable mutations. To date, differences exist in the application and NGS assays used as it remains unclear to what extent these variants may affect clinical decision making. In this survey-based study, we investigated the use of NGS in adult patients with glioblastoma in Switzerland. Methods: All eight primary care centres for Neuro-Oncology in Switzerland participated in this survey. The NGS assays used as well as the criteria for the application of NGS in newly diagnosed glioblastoma were investigated. Decision trees were analysed for consensus and discrepancies using the objective consensus methodology. Results: Seven out of eight centres perform NGS in patients with newly diagnosed glioblastoma using custom made or commercially available assays. The criteria most relevant to decision making were age, suitability of standard treatment and fitness. NGS is most often used in fitter patients under the age of 60 years who are not suitable for standard therapy, while it is rarely performed in patients in poor general health. Conclusion: NGS is frequently applied in glioblastomas in adults in Neuro-Oncology centres in Switzerland despite seldom changing the course of treatment to date. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article reviews possible clinical applications of positron emission tomography (PET) in patients with CNS lymphomas. PET allows quantitative assessment of brain tumor pathophysiology and biochemistry in vivo. Therefore, it provides different information about tumors when compared to histological or neuroradiological methods. In a diagnostic setting, PET cannot differentiate between primary lymphomas of the CNS, brain secondaries, or malignant gliomas, since various brain tumors share biochemical alterations. In HIV patients with contrast-enhancing brain tumors, however, data from the literature suggest that PET with the tracer F-18 fluoro-deoxyglucose may help to discriminate neoplastic (CNS lymphoma) from inflammatory (e.g. toxoplasmosis) lesions. Assuming that tumor biochemistry is highly abnormal in the most malignant parts of tumors, PET may also assist in defining targets for stereotactic biopsy. With regard to treatment evaluation, the prediction of individual treatment response is among the most challenging clinical applications of PET. On the one hand, this could be achieved on the basis of measures like tumor perfusion, oxygen consumption, or hypoxia. On the other hand, PET tracer methods may allow to quantify the expression of gene products following gene therapy. However, in CNS lymphoma patients these topics have yet not been addressed with PET. [ABSTRACT FROM AUTHOR]

Rubidium influx and Na - K-cotransport have been investigated in erythrocytes of mild essential hypertensives and normotensives devoid of familial hypertension. For measurement of cotransport Na-loaded/K-depleted erythrocytes were used while rubidium influx (with and without ouabain) was determined under physiological conditions. Both transport systems were linear in time, the interassay variances in a range of about 10%. The patients with essential hypertension exhibited a decreased rubidium influx compared to the normotensive controls. Ouabain-sensitive fluxes were not significantly different between the two groups, whereas ouabain-resistent rubidium influx was diminished in the group of the patients. Na - K-cotransport was also found to be decreased in essential hypertension. There was no correlation between cotransport and Rb-influx. The results indicate changes in cation fluxes in erythrocytes of essential hypertensives, the Na - K-cotransport being rather more altered than rubidium influx. It is speculated that hypertensive persons with reduced rubidium flux rates may represent a subpopulation of essential hypertension and that their high blood pressure may be additionally influenced by exogeneous factors e.g. enhanced sodium uptake. [ABSTRACT FROM AUTHOR]

Most mechanisms of drugs which are used in brain tumor chemotherapy are well characterized: alkylation of DNA components (nitrosoureas), binding with tubulin protein resulting in metaphase arrest (vincristine), chromatid breaks and chromosome translocations (procarbazine), or inhibition of ribonucleotide reductase (hydroxyurea) [1]. These drugs exert their effects mainly during certain cell cycle phases of proliferating cells, particularly when DNA is synthesized. From this it can be assumed that the efficacy of these drugs depends on the fraction of proliferating cells. Thus it would be of great importance to estimate the proliferation rate of brain tumors which could guide chemotherapy in individual patients. Positron emission tomography (PET) measures quantitatively the in vivo tissue uptake of tracer substances. In tumors, the uptake appears to be altered in a characteristic way determined by biochemical properties of tumor tissue. Some aspects of brain tumor metabolism which are theoretically related to proliferation have been investigated with PET. In the following, the literature is reviewed with regard to: 1) tracer substances whose uptake has been thought to reflect tumor malignancy (C-methionine,F-fluoro-deoxyglucose), and 2) tracers which theoretically could reflect mechanisms specifically related to DNA synthesis (C-putrescine, ligands for peripheral benzodiazepine receptors). [ABSTRACT FROM AUTHOR]

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We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron emission tomography (PET), 18 F-fluorodeoxyglucose (FDG),11 C-methionine (MET), and 82Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of the dynamic PET data revealed values for tumor plasma volume, blood-brain barrier transport rate constants and tracer distribution volume in the range of glioblastomas and meningiomas, or higher. Likewise, the steady-state accumulation of MET and FDG was increased. With regard to the known vascular composition of JPA, our data suggest that increased transport and distribution considerably contribute to the high net tracer uptake observed in this tumor. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a case of a 70-year-old man with recurrent tumour-like intracerebral masses, diagnosed as tumefactive demyelination (TD).

The age distribution and incidence of loss of heterozygosity (LOH) of 1p and 19q was analyzed in 85 oligodendroglial tumors WHO II and III. The peak of tumor manifestation was in the age group of 35 to 55 years. There was no association between age at diagnosis and LOH incidence. We conclude that the prognostic effect of age on survival is not mediated by LOH 1p/19q. [ABSTRACT FROM AUTHOR]

A 65-year-old female presented with Bannwarth's syndrome. Symptoms initially responded to antibiotics but soon progressed despite further adequate antibiotic treatment. Consistently absent antibody titres to Borrelia burgdorferi, repeated CSF examinations combined with an extensive search for tumour, revealed leukaemic meningitis secondary to uterine centrocytic-centroblastic lymphoma. The diagnostic steps required to elucidate the aetiology of meningopolyradiculitis, especially when chronic and progressive, are described. [ABSTRACT FROM AUTHOR]