Between-hospital variation in mortality and survival after glioblastoma surgery in the Dutch Quality Registry for Neuro Surgery

Purpose: Standards for surgical decisions are unavailable, hence treatment decisions can be personalized, but also introduce variation in treatment and outcome. National registrations seek to monitor healthcare quality. The goal of the study is to measure between-hospital variation in risk-standardized survival outcome after glioblastoma surgery and to explore the association between survival and hospital characteristics in conjunction with patient-related risk factors. Methods: Data of 2,409 adults with first-time glioblastoma surgery at 14 hospitals were obtained from a comprehensive, prospective population-based Quality Registry Neuro Surgery in The Netherlands between 2011 and 2014. We compared the observed survival with patient-specific risk-standardized expected early (30-day) mortality and late (2-year) survival, based on age, performance, and treatment year. We analyzed funnel plots, logistic regression and proportional hazards models. Results: Overall 30-day mortality was 5.2% and overall 2-year survival was 13.5%. Median survival varied between 4.8 and 14.9 months among hospitals, and biopsy percentages ranged between 16

Prognostic significance and mechanism of Treg infiltration in human brain tumors.

Contains fulltext : 89613.pdf (publisher's version ) (Closed access)Regulatory T cells (Tregs) accumulate in tumors and can contribute to the dismal immune responses observed in these tumors. We reported that the percentage of tumor infiltrating Tregs is strongly correlated with the WHO grade of the brain tumor. We now report on the clinical follow-up of this patient cohort (n=83). Subgroup analyses in patients with glioblastomas (n=29) showed a moderate, not significant, inverted association between Tregs and survival. We further show that Tregs in glioblastomas, in contrast to other tumor infiltrating effector lymphocytes, highly express the CCR4 chemokine receptor. Moreover, the CCR4 ligand CCL22 is secreted by glioblastomas and may explain the specific Treg accumulation seen in these tumors

In vivo 13C magnetic resonance spectroscopy of a human brain tumor after application of 13C-1-enriched glucose.

Contains fulltext : 88101.pdf (publisher's version ) (Closed access)OBJECTIVES: As a unique tool to assess metabolic fluxes noninvasively, (13)C magnetic resonance spectroscopy (MRS) could help to characterize and understand malignancy in human tumors. However, its low sensitivity has hampered applications in patients. The aim of this study was to demonstrate that with sensitivity-optimized localized (13)C MRS and intravenous infusion of [1-(13)C]glucose under euglycemia, it is possible to assess the dynamic conversion of glucose into its metabolic products in vivo in human glioma tissue. MATERIALS AND METHODS: Measurements were done at 3 T with a broadband single RF channel and a quadrature (13)C surface coil inserted in a (1)H volume coil. A (1)H/(13)C polarization transfer sequence was applied, modified for localized acquisition, alternatively in two (50 ml) voxels, one encompassing the tumor and the other normal brain tissue. RESULTS: After about 20 min of [1-(13)C]glucose infusion, a [3-(13)C]lactate signal appeared among several resonances of metabolic products of glucose in MR spectra of the tumor voxel. The resonance of [3-(13)C]lactate was absent in MR spectra from contralateral tissue. In addition, the intensity of [1-(13)C]glucose signals in the tumor area was about 50% higher than that in normal tissue, likely reflecting more glucose in extracellular space due to a defective blood-brain barrier. The signal intensity for metabolites produced in or via the tricarboxylic acid (TCA) cycle was lower in the tumor than in the contralateral area, albeit that the ratios of isotopomer signals were comparable. CONCLUSION: With an improved (13)C MRS approach, the uptake of glucose and its conversion into metabolites such as lactate can be monitored noninvasively in vivo in human brain tumors. This opens the way to assessing metabolic activity in human tumor tissue.01 juni 201

Observer variability of reference tissue selection for relativecerebral blood volume measurements in glioma patients

OBJECTIVES: To assess observer variability of different reference tissues used for relative CBV (rCBV) measurements in DSC-MRI of glioma patients. METHODS: In this retrospective study, three observers measured rCBV in DSC-MR images of 44 glioma patients on two occasions. rCBV is calculated by the CBV in the tumour hotspot/the CBV of a reference tissue at the contralateral side for normalization. One observer annotated the tumour hotspot that was kept constant for all measurements. All observers annotated eight reference tissues of normal white and grey matter. Observer variability was evaluated using the intraclass correlation coefficient (ICC), coefficient of variation (CV) and Bland-Altman analyses. RESULTS: For intra-observer, the ICC ranged from 0.50-0.97 (fair-excellent) for all reference tissues. The CV ranged from 5.1-22.1 % for all reference tissues and observers. For inter-observer, the ICC for all pairwise observer combinations ranged from 0.44-0.92 (poor-excellent). The CV ranged from 8.1-31.1 %. Centrum semiovale was the only reference tissue that showed excellent intra- and inter-observer agreement (ICC>0.85) and lowest CVs (<12.5 %). Bland-Altman analyses showed that mean differences for centrum semiovale were close to zero. CONCLUSION: Selecting contralateral centrum semiovale as reference tissue for rCBV provides the lowest observer variability. KEY POINTS: * Reference tissue selection for rCBV measurements adds variability to rCBV measurements. * rCBV measurements vary depending on the choice of reference tissue. * Observer variability of reference tissue selection varies between poor and excellent. * Centrum semiovale as reference tissue for rCBV provides the lowest observer variability

3'-Deoxy-3'-18F-Fluorothymidine PET-Derived Proliferative Volume Predicts Overall Survival in High-Grade Glioma Patients

Item does not contain fulltext3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a radiopharmaceutical depicting tumor cell proliferation with PET. In malignancies of the lung, breast, head and neck, digestive tract, brain, and other organs, quantitative assessment of (18)F-FLT targeting has been shown to correlate with the proliferation marker Ki-67 and with clinical outcome measures such as time to progression and overall survival (OS). The aim of this study was to assess various PET segmentation methods to estimate the proliferative volume (PV) and their prognostic value for OS in patients with suspected high-grade glioma. METHODS: Twenty-six consecutive patients underwent preoperative (18)F-FLT PET/CT and T1-weighted MRI of the brain after contrast application. The maximum standardized uptake value (SUV(max)) of all tumors was calculated, and 3 different segmentation methods for estimating the PV were used: the 50% isocontour of the SUV(max) signal for the PV(50%), the signal-to-background ratio (SBR) for an adaptive threshold delineation (PV(SBR)) method, and the iterative background-subtracted relative threshold level (RTL) method to estimate the PV(RTL). The prognostic value of the SUV(max) and the different PVs for OS were assessed. RESULTS: Twenty-two patients had glioblastoma multiforme, 2 had anaplastic oligodendroglioma, 1 had anaplastic ependymoma, and 1 had anaplastic astrocytoma. The median OS was 397 d (95% confidence interval, 204-577); 19 patients died during the follow-up period. The PV(SBR) showed a significantly (P = 0.002) better association with OS than did SUV(max), PV(RTL), and PV(50%). Receiver-operating-characteristic analysis resulted in a threshold volume for the PV(SBR) of 11.4 cm(3), with a sensitivity and specificity of 70% and 83%, respectively, for the prediction of OS. Kaplan-Meier analyses showed a significant discrimination between short and long OS (P = 0.024, log rank) for this threshold. CONCLUSION: The PV as determined by (18)F-FLT PET is associated with OS in high-grade malignant gliomas. The SBR method yielded the best results to predict short and long OS

Between-hospital variation in mortality and survival after glioblastoma surgery in the Dutch Quality Registry for Neuro Surgery

Scientific Assessment and Innovation in Neurosurgical Treatment Strategie