The proteomic response in glioblastoma in young patients.

Increasing age is an important prognostic variable in glioblastoma (GBM). We have defined the proteomic response in GBM samples from 7 young patients (mean age 36 years) compared to peritumoural-control samples from 10 young patients (mean age 32 years). 2-Dimensional-gel-electrophoresis, image analysis, and protein identification (LC/MS) were performed. 68 proteins were significantly altered in young GBM samples with 29 proteins upregulated and 39 proteins downregulated. Over 50 proteins are described as altered in GBM for the first time. In a parallel analysis in old GBM (mean age 67 years), an excellent correlation could be demonstrated between the proteomic profile in young GBM and that in old GBM patients (r(2) = 0.95) with only 5 proteins altered significantly (p < 0.01). The proteomic response in young GBM patients highlighted alterations in protein-protein interactions in the immunoproteosome, NFkB signalling, and mitochondrial function and the same systems participated in the responses in old GBM patients.

Interactions among mitochondrial proteins altered in glioblastoma.

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥ 2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein-protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology.

Overcoming fear and anxiety during awake resection of brain tumours: family support can be pivotal to a successful outcome.

Patient anxiety and fear about an awake craniotomy can affect the patient's choice about having an operation despite comprehensive pre-operative counselling. We report three cases in which a family member came into theatre during the procedure to support the patient during surgery. All three cases, which involved intra-operative cortical and subcortical stimulations and intra-operative patient testing, were successfully completed with major tumour resections and no post-operative complications. We suggest that family support should be considered in patients who have extreme fear and anxiety about awake surgery.

Using general practitioners with an extended role in spinal practice for the initial assessment of patients referred to spinal surgeons: preliminary experience and challenges.

AIM: To describe experience using general practitioners (GPs), with an extended role (GPwER) in spinal medicine, to expedite assessment, triage, and management of patients referred from primary care for specialist spinal surgical opinion. BACKGROUND: Low back and neck pain are common conditions in primary care. Indiscriminate or inappropriate referral to a spinal surgeon contributes to long waiting times. Previous attempts at triaging patients who really require a surgical opinion have used practice nurses, physiotherapists, clinical algorithms, and interdisciplinary screening clinics. METHODS: Within the setting of an independent spinal care centre, we have used GPs specially trained in spinal practice to expedite the assessment and triage of new referrals between 2015 and 2021. We reviewed feedback from a Patient Satisfaction Questionnaire and the postgraduate backgrounds, training, practice with regard to triage of new referrals, and experiences of the GPs who were recruited. FINDINGS: Six GPwER had a mean of 26 years of postgraduate experience before appointment (range 10-44 years). The first four GPwER, appointed between 2015 and 2018, underwent an ad hoc in-house, interdisciplinary training programme and saw 2994 new patients between 2016 and 2020. After GPwER, assessment in only 18.9% (range 12.6 to 22.7%) of these patients was a spinal surgical opinion deemed necessary. Waiting times to see the spinal surgeon remained at 6-8 weeks despite a three-fold annual increase (from 340 to 1058) in new referrals. A Patient Satisfaction Questionnaire revealed high levels of satisfaction with the performances of the GPwER across seven dimensions. A dedicated training programme was designed in 2020, and the last two appointees underwent 20 h of clinical teaching prior to practice. Initial experience using GPwER, here termed 'Spinal Clinicians', suggests they are efficient at screening for patients needing spinal surgical referral. Establishing a recognised training programme, assessment, and certification for these practitioners are the next challenges.

Imaging incidence and type in primary care patients with low back pain: a cross-sectional study on new referrals to an Australian specialist spinal surgical centre.

Introduction Low back pain (LBP) is common and a significant cause of morbidity. Many patients receive inappropriate imaging for LBP in primary care. Aim To explore the incidence and type of spinal imaging conducted for LBP patients referred from general practice for specialist surgical opinion, and evaluate whether imaging conformed to clinical guidelines. Methods Audit of a sequential cohort (n = 100) of new LBP patients referred from primary care for specialist opinion at a suburban Australian capital city independent Spinal Centre. Results In the 6 months before referral, 90% (95% CI 83-95%) of patients underwent spinal imaging. Imaging was performed in 95% of those who did and 79% of those who did not meet guidelines for radiological investigation. 35% of patients were inappropriately imaged and 3% inappropriately not imaged. Spinal computed tomography (CT) imaging was used in 52% of patients, magnetic resonance imaging (MRI) in 42% and image-guided lumbar spinal interventional procedures in 28%. Discussion Most patients with LBP referred for surgical opinion have diagnostic radiological investigations whether or not it is indicated by clinical guidelines. The more frequent use of spinal CT compared to MRI may be due to idiosyncrasies of the Australian Medicare Benefits Schedule (MBS) rebate system. The findings of this pilot study provide support for the changes recommended by the 2016 MBS Review Taskforce on LBP that permit GP access to subsidised lumbar MRI, while constraining access to lumbar CT, and provide novel data about spinal imaging and practice in this cohort of patients.

Surgical decompression for cerebral oedema in acute ischaemic stroke.

BACKGROUND: Large cerebral infarction has a high case fatality. Despite the use of conventional medical treatments such as hyperventilation, mannitol, diuretics, corticosteroids and barbiturates, the outcome of this condition remains poor. Decompressive surgery to relieve intracranial pressure is performed in some cases, although evidence of any clinical benefits has not been available until recently. This is an update of a Cochrane review first published in 2002. OBJECTIVES: To examine the effects of decompressive surgery in patients with massive acute ischaemic stroke complicated with cerebral oedema, and to judge whether decompressive surgery is effective in improving survival or survival free of severe disability. SEARCH METHODS: We searched the Cochrane Stroke Group's Trials Register (last searched October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 7), MEDLINE (1966 to October 2010), EMBASE (1980 to October 2010) and Science Citation Index (October 2010). We also searched the reference lists of all relevant articles. SELECTION CRITERIA: Randomised controlled studies of decompressive surgery plus medical treatment versus medical treatment alone in patients with clinically and radiologically confirmed cerebral infarcts complicated with cerebral oedema. DATA COLLECTION AND ANALYSIS: One author assessed the titles and retrieved the relevant studies. The same author extracted data, with discussion among all authors for clarification. Outcomes were death at the end of follow-up, death or disability defined as the modified Rankin Scale (mRS) > 3 at the end of follow-up, death or severe disability defined as mRS > 4 at 12 months and disability defined as mRS 4 or 5 at 12 months. The results are given using the Peto odds ratio (Peto OR) with 95% confidence intervals (CIs). MAIN RESULTS: We included three trials in this review, involving 134 patients who were 60 years of age or younger. The time window for the intervention was 30 hours from stroke onset in two studies and 96 hours in one study. All trials were stopped early. Surgical decompression reduced the risk of death at the end of follow-up (OR 0.19, 95% CI 0.09 to 0.37) and the risk of death or disability defined as mRS > 4 at 12 months (OR 0.26, 95% CI 0.13 to 0.51). Death or disability defined as mRS > 3 at the end of follow-up was no different between the treatment arms (OR 0.56, 95% CI 0.27 to 1.15). AUTHORS' CONCLUSIONS: Surgical decompression lowers the risk of death and death or severe disability defined as mRS > 4 in selected patients 60 years of age or younger with a massive hemispheric infarction and oedema. Optimum criteria for patient selection and for timing of decompressive surgery are yet to be defined. Since survival may be at the expense of substantial disability, surgery should be the treatment of choice only when it can be assumed, based on their preferences, that it is in the best interest of patients. Since all the trials were stopped early, an overestimation of the effect size cannot be excluded.

Preoperative quality of life in patients with degenerative spinal disorders: many are worse than patients with brain tumours and cancer.

BACKGROUND: This study compared prospectively the quality of life (QoL), function and mood of patients about to undergo surgery for either an intracranial supratentorial tumour or a spinal degenerative condition. The QoL scores were also compared to that of cohorts with a range of extracranial cancers. MATERIAL AND METHODS: The study took place in a Scottish NHS Neurosurgical Unit. Patients were assessed on the day prior to surgery for their QoL (European Organisation for Research and Treatment of Cancer (EORTC)-QLQ C30), mood status (Hospital Anxiety and Depression Score), Performance status (Karnosky Score, timed 10-m walk) and disability (Barthel Disability Index). All tests were performed by a single trained psychologist. RESULTS: Between 2007 and 2009, 101 patients with intracranial tumours, 75 age- and gender-matched patients with degenerative spinal disorders and 80 healthy adults were evaluated. There was no difference in the mood or disability scores between the two patient cohorts, but mood was significantly worse than a matched healthy cohort. The spinal cohort had significantly worse scores on the Karnovsky Scale, timed 10-m walk and for Global Health than those of the brain tumour cohort. They also had worse mean scores on all five functional scales, as well as six of the nine symptom/single-item scales, of the EORTC QLQ C30. SUMMARY: Patients with degenerative spinal disorders awaiting surgery on the NHS have significantly impaired QoL in multiple domains as well as other functional and mood disorders. Not only are their scores worse than a brain tumour cohort but they are also worse than many cancer cohorts described in the literature using the EORTC QLQ C30. These findings suggest that preoperative care, assessment and management of NHS patients with degenerative spinal disorders could be improved and that the EORTC QLQ C30 may be a useful tool for audit purposes in this cohort.

NICE guidance on the use of carmustine wafers in high grade gliomas: a national study on variation in practice.

BACKGROUND: Multidisciplinary team (MDT) working in oncology aims to improve outcomes for patients with cancer. One role is to ensure the implementation of best practice and National Institute for Health and Clinical Excellence (NICE) guidance. In this study, we have assessed the role of MDT in implementing the TA121 appraisal of the use of carmustine wafers in high grade gliomas. METHODS: 296 patients with high-grade glioma suitable for maximal resection were recruited from 17 Neurosurgical Centres. The number of patients treated with carmustine wafers and reasons for not using this were recorded. Complications at 48 hours post-operatively and at 6 weeks post-radiotherapy were recorded. RESULTS: 94/296 (32%) of suitable patients received carmustine wafers. In 55% of cases carmustine was not used due to either surgeon preference or a lack of an MDT decision. There was no increased complication rate with carmustine use at either 48 hours post-surgery or at 6 weeks post radiotherapy. Use of carmustine wafers did not decrease access to and use of chemoradiotherapy. CONCLUSIONS: One third of patients suitable for carmustine wafers received them. Their use was neither associated with more frequent complications, nor decreased use of chemoradiotherapy. Implementation of NICE TA121 Guidance is extremely variable in different MDTs across the United Kingdom.

Clinical utility and reproducibility of surface electromyography in individuals with chronic low back pain: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Chronic low back pain (CLBP) is one of the most common disorders presenting in primary healthcare. Kinematic studies of low lumbar pelvic mobility allied with surface electromyography (sEMG) may assist in the assessment and management of CLBP. However, the applicability in the use of sEMG in the clinical setting remains uncertain. In this protocol, we aim to review the clinical utility and reproducibility of the sEMG component of these kinematic studies in patients with CLBP. METHODS AND ANALYSIS: This protocol was informed by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) and results will be reported in line with the PRISMA. Searches will be conducted on PubMed, Scopus, Web of Science, Embase, CINAHL and Google Scholar databases, along with a comprehensive review of grey literature. Two reviewers will conduct the searches and independently screen them, according to title and abstract. Two independent reviewers will then assess the full-text versions of those selected articles and assess the risk of bias using the defined protocol inclusion criteria. The risk of bias within the studies included will be assessed via the Quality Assessment of Diagnostic Accuracy Studies tool, V.2 and the Grading of Recommendations Assessment, Development and Evaluation guidelines will be used to assess certainty of evidence for recommendations based on the risk of bias findings. Meta-analysis will be conducted where appropriate on groups of studies with low heterogeneity. In instances of higher heterogeneity, meta-synthesis will instead be completed, comparing results in terms of increased or decreased clinical utility and/or reproducibility of sEMG. ETHICS AND DISSEMINATION: Ethics approval was not required for this research. It is anticipated that the results will influence the use, interpretation and further development of sEMG in management and assessment of these patients. PROSPERO REGISTRATION NUMBER: CRD42021273936.

Network generation enhances interpretation of proteomic data from induced apoptosis.

Thirteen proteins (identified with 2-D gels and MALDI-TOF MS) are significantly altered during staurosporine-induced apoptosis in SH-SY5Y cells. To gain further insight into the integrated cellular response to apoptosis, we have investigated whether a network can be generated of direct and indirect interactions between these 13 proteins. A network that contains 12 out of the 13 proteins was generated using Ingenuity Pathway Analysis (IPA) and this network is dominated (89%) by direct protein-protein interactions. This network scored 34 with IPA. Bootstrapping 1000 random lists of 13 proteins suggested that the frequency of this score occurring by chance was 1 in 500. We examined whether subsets of proteins such as HSPs, which were elevated after staurosporine, had a disproportionate impact on the network generated. There was no evidence that any subset of 8 from the 13 proteins contributed disproportionately to the network. Network generation, using IPA, identified common features (such as endoplasmic reticular stress protein interactions) in apoptotic studies from different laboratories. The generation of protein interaction networks clearly enhances the interpretation of proteomic data, but only when interpreted cautiously, particularly in respect of statistical analyses.

Pretreatment tumoural perfusion correlates with an imaging-based response to dexamethasone in patients with glioblastoma multiforme.

Imaging-based markers of treatment response are increasingly being used in studies of brain-tumour therapies, for evaluating novel treatments and further understanding of existing therapies. An ultimate goal of these studies is to identify pre- or early-stage treatment imaging biomarkers that enable prediction of subsequent treatment response. We hypothesised that pretreatment MRI-based measurements of tumoural perfusion may provide a suitable imaging-based biomarker for prediction of subsequent treatment response and evaluated this in a group of nine high-grade glioma patients undergoing dexamethasone treatment. A strong positive correlation was observed between tumoural blood flow (R(2)=0.90, p<0.001) and tumoural blood volume (R(2)=0.76, p=0.002), and subsequent treatment response as measured by alterations in tumour leakage properties. These preliminary results indicate that measurements of tumoural perfusion may provide useful imaging biomarkers for predicting treatment response to dexamethasone and would therefore also be worth evaluating in newer emerging therapies.

Assessment of physiological parameters within glioblastomas in awake patients: a prospective clinical study.

OBJECT: Multiparametric brain monitoring probes now make it possible to measure cerebral physiology. This prospective clinical study was designed to evaluate the pathophysiological environment of tumoural and peritumoural tissue O(2), CO(2), pH, HCO(3)- and temperature of awake patients with glioblastoma. METHODS: A Neurotrend multiparametric sensor was placed using intraoperative image guidance into glioblastoma after biopsy under general anesthetic. Postoperative monitoring was then performed in awake patients. RESULTS: Twelve patients were recruited and monitoring was performed, and well tolerated in 9 for up to 22 hrs. Mean glioblastoma tumour values were: tissue oxygen pressure (PtiO(2)) 21.0 mmHg, standard deviation +/- 7.9; PtiCO(2) 60.2 +/- 17.2 mmHg; temperature 36.9 +/- 0.4 degrees C, pH 7.08 + 0.2; and HCO(3) 17.1 +/- 3.7. Mean peritumoural brain values in 5 patients were PtiO(2) 29.1 +/- 27.6 mmHg; PtiCO(2) 48.6 +/- 7.0 mmg; temperature 36.4 +/- 0.6 degrees C; pH 7.20 +/- 0.09 and HCO(3) 19.1 +/- 3.5. There were trends for the PtiO(2) to decrease with increasing brain depth. As glioblastoma PtiCO(2) levels decreased, pH increased. There were no relationships between either tumoural PtiO(2) and pH, or PtiO(2) and PtiCO(2), however there were large intra- and inter-tumoural variation in monitoring values. There were technical problems in some patients with the Neurotrend sensor that limited its application, and that compromised aspects of data collection and interpretation, particularly of PtiO(2). CONCLUSION: This study has shown that this novel approach to monitoring glioma pathophysiology is feasible and well tolerated by patients. The data, much of which is novel, contributes to the knowledge of glioblastoma pathophysiology. However, further study and clinical exploitation awaits the development of a more reliable multiparametric sensor.

Recruitment difficulties in brain tumour patients cause participation bias: findings from a neuropsychological study of adult inpatients with supratentorial intracranial tumours.

PURPOSE: Patients who participate in questionnaire surveys, clinical studies and clinical trials can be different from patients who do not participate. The occurrence and direction of this response, participation or ascertainment bias is unpredictable, and can harm the external validity of medical research. METHODS: We compared the characteristics of patients with intracranial tumours who participated in a psychological study of inspection time with the characteristics of patients who did not participate for a number of reasons. RESULTS: Of 178 newly diagnosed adults with intracranial tumours, 136 (76%) were eligible, of whom 76 (56%) participated and 34 (25%) declined. There were no significant differences in terms of age and sex of the patients who participated and those who declined. When the participation group was combined with those who were ineligible and those who declined, the majority of patients in the combined cohort (n = 152) had a WHO grade III or IV glioma (high-grade glioma) (48.0%), and only 13.2% had a WHO grade I or II glioma (low-grade glioma). However, only 38.2% of those who participated had a WHO grade III or IV glioma, and 23.7% had a WHO grade I or II glioma. Comparisons of the participation vs. ineligible and declined groups revealed there was a significant difference (p = 0.002) between the ratio of high-grade to low-grade gliomas in the total and recruited cohorts. Comparisons of only the participation vs. declined groups approached significance (p = 0.051). WHO grade III and IV glioma patients were under-represented, and WHO grade I or II glioma patients were over-represented in the study group. CONCLUSIONS: Noninterventional, non-therapeutic applied neuropsychological studies in neuro-oncology are susceptible to bias since the spectrum of neuropathologies in recruited patients can be significantly different from that of the total cohort. These data could help anticipate recruitment rates for applied neuropsychological studies in clinical neuro-oncology and may help anticipate likely selection biases amongst those who participate.

Quantitative assessment of intracranial tumor response to dexamethasone using diffusion, perfusion and permeability magnetic resonance imaging.

There is increasing interest in obtaining quantitative imaging parameters to aid in the assessment of tumor responses to treatment. In this study, the feasibility of performing integrated diffusion, perfusion and permeability magnetic resonance imaging (MRI) for characterizing responses to dexamethasone in intracranial tumors was assessed. Eight patients with glioblastoma, five with meningioma and three with metastatic carcinoma underwent MRI prior to and 48-72 h following dexamethasone administration. The MRI protocol enabled quantification of the volume transfer constant (K(trans)), extracellular space volume fraction (nu(e)), plasma volume fraction (nu(p)), regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), longitudinal relaxation time (T(1)) and mean diffusivity (D(av)). All subjects successfully completed the imaging protocol for the presteroid and poststeroid scans. Significant reductions were observed after the treatment for K(trans), nu(e) and nu(p) in enhancing tumor as well as for T(1) and D(av) in the edematous brain in glioblastoma; on the other hand, for meningioma, significant differences were seen only in edematous brain T(1) and D(av). No significant difference was observed for any parameter in metastatic carcinoma, most likely due to the small sample size. In addition, no significant difference was observed for enhancing tumor rCBF and rCBV in any of the tumor types, although the general trend was for rCBV to be reduced and for rCBF to be more variable. The yielded parameters provide a wealth of physiologic information and contribute to the understanding of dexamethasone actions on different types of intracranial tumors.

Microsomal prostaglandin E synthase-1 regulates human glioma cell growth via prostaglandin E(2)-dependent activation of type II protein kinase A.

Dysregulation of enzymes involved in prostaglandin biosynthesis plays a critical role in influencing the biological behavior and clinical outcome of several tumors. In human gliomas, overexpression of cyclooxygenase-2 has been linked to increased aggressiveness and poor prognosis. In contrast, the role of prostaglandin E synthase in influencing the biological behavior of human gliomas has not been established. We report that constitutive expression of the microsomal prostaglandin E synthase-1 (mPGES-1) is associated with increased prostaglandin E(2) (PGE(2)) production and stimulation of growth in the human astroglioma cell line U87-MG compared with human primary astrocytes. Consistently, pharmacologic and genetic inhibition of mPGES-1 activity and expression blocked the release of PGE(2) from U87-MG cells and decreased their proliferation. Conversely, exogenous PGE(2) partially overcame the antiproliferative effects of mPGES-1 inhibition and stimulated U87-MG cell proliferation in the absence of mPGES-1 inhibitors. The EP2/EP4 subtype PGE(2) receptors, which are linked to stimulation of adenylate cyclase, were expressed in U87-MG cells to a greater extent than in human astrocytes. PGE(2) increased cyclic AMP levels and stimulated protein kinase A (PKA) activity in U87-MG cells. Treatment with a selective type II PKA inhibitor decreased PGE(2)-induced U87-MG cell proliferation, whereas a selective type I PKA inhibitor had no effect. Taken together, these results are consistent with the hypothesis that mPGES-1 plays a critical role in promoting astroglioma cell growth via PGE(2)-dependent activation of type II PKA.

Imaging signatures of meningioma and low-grade glioma: a diffusion tensor, magnetization transfer and quantitative longitudinal relaxation time MRI study.

Differentiation of cerebral tumor pathology currently relies on interpretation of conventional structural MRI and in some cases histology. However, more advanced MRI methods may provide further insight into the organization of cerebral tumors and have the potential to aid diagnosis. The objective of this study was to use multimodal quantitative MRI to measure the imaging signatures of meningioma and low-grade glioma (LGG). Nine adults with meningioma and 11 with LGG were identified, and underwent standard structural, quantitative longitudinal relaxation time (T1) mapping, magnetization transfer and diffusion tensor MRI. Maps of mean (〈D〉), axial (λAX) and radial (λRAD) diffusivity, fractional anisotropy (FA), magnetization transfer ratio (MTR) and T1 were generated on a voxel-by-voxel basis. Using structural and echo-planar T2-weighted MRI, manual region-of-interest segmentation of brain tumor, edema, ipsilateral and contralateral normal-appearing white matter (NAWM) was performed. Differences in imaging signatures between the different tissue types, both absolute mean values and ratios relative to contralateral NAWM, were assessed using t-tests with statistical significance set at p<0.05. For both absolute mean values and ratios relative to contralateral NAWM, there were significant differences in 〈D〉, λAX, λRAD, FA, MTR and T1 between meningioma and LGG tumor tissue, respectively. Only T1 and FA differed significantly between edematous tissue associated with the two tumor types. These results suggest that multimodal MRI biomarkers are significantly different, particularly in tumor tissue, between meningioma and LGG. By using quantitative multimodal MRI it may be possible to identify tumor pathology non-invasively.

Meningiomas.

Meningiomas are by far the most common tumours arising from the meninges. Progressive enlargement of the tumour leads to focal or generalised seizure disorders or neurological deficits caused by compression of adjacent neural tissue. Surgery remains the primary treatment of choice, although the use of fractionated radiotherapy or stereotactic single-dose radiosurgery is increasing for meningiomas that are incompletely excised, surgically inaccessible, or recurrent and either atypical or anaplastic. Although most meningiomas have good long-term prognosis after treatment, there are still controversies over management in a proportion of cases. We review various features of meningioma biology, diagnosis, and treatment and provide an overview of the current rationale and evidence base for the various therapeutic approaches.

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma.

A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to confirm these results. Two hundred forty patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology. Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P

Measurements of water diffusion and T1 values in peritumoural oedematous brain.

Using quantitative MR imaging, values for the mean water diffusivity (), the diffusion anisotropy and the longitudinal relaxation time (T1) were measured for tumour, oedematous and normal brain in a group of treatment-naive patients with high-grade glioma and low-grade meningioma. The mean values of and T1 for enhancing tumour and oedematous brain were significantly higher in high-grade glioma than meningioma, while the diffusion anisotropy was reduced. Values of and T1 were also positively correlated in oedematous brain in both pathologies. There was, however, no clear evidence of similar correlations in apparently normal contralateral white matter. Such results illustrate the potential of MR imaging to improve not only the characterization of brain oedema, but also the monitoring of treatment response.