CovidNeuroOnc: A UK multicenter, prospective cohort study of the impact of the COVID-19 pandemic on the neuro-oncology service

BackgroundThe COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumors.MethodsWe performed a multicenter prospective study of all adult patients discussed in weekly neuro-oncology and skull base multidisciplinary team meetings who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumor between 01 April and 31 May 2020. All patients had at least 30-day follow-up data. Descriptive statistical reporting was used.ResultsThere were 1357 referrals for newly diagnosed or recurrent intracranial tumors across 15 neuro-oncology centers. Of centers with all intracranial tumors, a change in initial management was reported in 8.6% of cases (n = 104/1210). Decisions to change the management plan reduced over time from a peak of 19% referrals at the start of the study to 0% by the end of the study period. Changes in management were reported in 16% (n = 75/466) of cases previously recommended for surgery and 28% of cases previously recommended for chemotherapy (n = 20/72). The reported SARS-CoV-2 infection rate was similar in surgical and non-surgical patients (2.6% vs. 2.4%, P > .9).ConclusionsDisruption to neuro-oncology services in the UK caused by the COVID-19 pandemic was most marked in the first month, affecting all diagnoses. Patients considered for chemotherapy were most affected. In those recommended surgical treatment this was successfully completed. Longer-term outcome data will evaluate oncological treatments received by these patients and overall survival

Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE) and the biomarker-surrogacy (BioSurrogate) evaluation schema (BSES)

<p>Abstract</p> <p>Background</p> <p>Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i) formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii) determine what blood pressure reduction would predict a stroke benefit.</p> <p>Methods</p> <p>We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE), below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP), a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3).</p> <p>Results</p> <p>In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and diastolic blood pressure was an A grade surrogate endpoint for stroke prevention. In comparison, using the same stroke data sets, no STEs could be estimated for cardiovascular (CV) mortality or all-cause mortality reduction, although the STE for CV mortality approached 25 mmHg for systolic blood pressure.</p> <p>Conclusions</p> <p>In this report we provide the first surrogate threshold effect (STE) values for systolic and diastolic blood pressure. We suggest the STEs have face and content validity, evidenced by the inclusivity of trial populations, subject populations and pharmacologic intervention populations in their calculation. We propose that the STE and STEP metrics offer another method of evaluating the evidence supporting surrogate endpoints. We demonstrate how surrogacy evaluations are strengthened if formally evaluated within specific-context evaluation frameworks using the Biomarker- Surrogate Evaluation Schema (BSES3), and we discuss the implications of our evaluation of blood pressure on other biomarkers and patient-reported instruments in relation to surrogacy metrics and trial design.</p

Brain Tumors: Planning and Monitoring Therapy with Positron Emission Tomography

The term ‘brain tumor’ encompasses a broad spectrum of individual pathologies, affecting a heterogeneous patient population, with few clear etiological factors and widely varying prognostic implications. These tumors range from localized, potentially curable, benign lesions in childhood to rapidly progressive malignant disease with an increasing prevalence in an ageing population. Most primary brain tumors in adults are inherently infiltrating lesions, giving rise to progressive symptoms for the patient and adding to the difficulty of treating the condition without imposing permanent neurological deficits. Despite improvements in diagnostic techniques and potential therapies, outcomes for these patients have not improved substantially over recent years. In fact, the average “years of life lost” by a patient with a tumor of the central nervous system was more than that for any other cancer in one recent review (Burnet et al. 2005). This highlights the need to optimize current management as well as the necessity for further research and development

Long-term safety of biologics in the treatment of psoriasis

Manisha R Panchal,1 Helen Coope,2 D John McKenna,3 Anton B Alexandroff31Department of Dermatology, Sherwood Forest Hospitals, Kingsmill Hospital, Nottinghamshire, 2Novartis Pharmaceuticals UK Ltd, West Sussex, 3Department of Dermatology, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, UKAbstract: Biologics are novel and important agents in the treatment of severe psoriasis. These agents block specific molecular steps in the inflammatory cascade, thereby reducing activation and proliferation of keratinocytes. Prescreening for biologic agents and careful monitoring of patients is important. There are four biologics currently licensed and used in the treatment of psoriasis in the European Union. This is an evidence-based review examining clinical trials and focusing on the long-term safety data for four biologic agents. Current British Association of Dermatology guidance for the use of biologics in psoriasis and guidelines on the management of psoriasis from the National Institute for Health and Clinical Excellence have been used. Advances on safety information since 2009 in clinical trials are reviewed. The results show that overall there is no statistical significance in the incidence of adverse effects of biologics versus placebo. However, there are serious adverse effects that are reported for biologics that need to be assessed for and addressed promptly. Results of studies discussing major adverse cardiovascular events are also reviewed.Keywords: psoriasis, biologic agents, safety profile, major cardiovascular event

Correlation of pre-operative language fMRI with intra-operative direct cortical stimulation findings in glioma surgery identifies potential false positive fMRI activations with conventional analysis

BACKGROUND: Functional MRI (fMRI) has an increasingly established role in surgical planning for glioma patients. However, the presence of neuro-vascular decoupling in the vicinity of the tumor, along with other tumor specific phenomena, raises at least theoretical concerns of potential inaccuracies. Several studies have attempted to correlate fMRI findings with cortical mapping performed using direct cortical stimulation (DCS). Results with respect to language mapping in particular have not been consistent and have focused upon investigating the sensitivity of fMRI to detect eloquent tissue. The possibility of false positive activations that could lead to regions of tumor being incorrectly labeled as inoperable has not been fully explored, in part due to the challenge of accurately recording DCS findings. METHODS: Ten patients with suspected primary or recurrent low-grade gliomas underwent pre-operative fMRI including 3-4 language paradigms on a Phillips 3T Achieva scanner. Comprehensive neuropsychological assessment was also completed prior to awake craniotomy. fMRI data processed using Phillips proprietary IViewBOLD was made available using the BrainLab VectorVision neuro-navigation system for planning of the craniotomy. The surgeon was blinded to fMRI outcomes for the duration of cortical mapping to minimize bias. DCS was completed using a bipolar stimulator tracked continuously using the BrainLab system networked via the VVLink interface to a research system running 3D Slicer. DCS outcomes were recorded by the surgeon using a panel of footswitches to trigger a custom logging module. fMRI data was re-processed using Statistical Parametric Mapping (SPM) 8 to generate t-statistic maps with a simple threshold of 3 applied analogous to the standard clinical implementation. DCS outcomes within 10mm of a cluster of ≥10 voxels above the threshold were analyzed. RESULTS: A mean of 125.4 [range 64-178] unique DCS outcomes were recorded per subject with 60 [32-100] being at the current level at which a positive outcome was noted. A total of 15 fMRI activation clusters above the threshold level could be evaluated across the 10 patients [0-3 per patient]. 7 activations (46.7%) were confirmed with positive DCS findings (i.e. speech disturbance induced by DCS). However, 8 activations (53.3%) from 4 patients had more than one negative DCS finding and no positive DCS outcomes within a 10mm radius. 10 individual positive DCS outcomes [0-4 per patient] with no corresponding fMRI activation were also noted. CONCLUSION: The presence of fMRI activations that were not confirmed on DCS, the current gold standard for cortical mapping, raises the possibility of false positive fMRI activations. This could unnecessarily restrict tumor resections with a potential negative impact upon outcome and merits further investigation in particular as to the potential benefit of alternate fMRI analysis approaches