Invloed van groeisnelheid op de effectiviteit van Gamma Knife-behandeling van vestibulair schwannomen

Deze studie is gericht op het bepalen van de invloed van de groeisnelheid van vestibulair schwannomen (VS) op de effectiviteit van een Gamma Knife (GK)-behandeling. Goal: This study focused on determining the influence of the growth rate of vestibular schwannoma (VS) on the effectiveness of a Gamma Knife (GK) treatment.\u3cbr/\u3eMethods: All patients treated with GK after a wait-and-scan policy were included. MRI scans before and after treatment were volumetrically assessed and the pre-treatment volume doubling time (VDT) was calculated. Statistical analyses were applied to analyse the influence.\u3cbr/\u3eResults: The resulting patient cohort contained 311 patients with a median follow-up of 60 months, including 35 patients for which the treatment was not effective. Kaplan-Meier analyses resulted in significant differences between slow- and fast-growing VS in the 5- and 10-year success percentages (log-rank, p=0.001): 97.3% and 86.0% for the slow-growing tumors and 85.5% and 67.6% for the fast-growing tumors, respectively. Influence of the VDT on the treatment result was also determined in a Cox regression. The resulting model showed a significant (p=0.045), but small effect of the VDT on the hazard ratios. \u3cbr/\u3eConclusions: By employing our unique, large database with long follow-up times, we were able to show the influence of the growth rate of VS on the GK treatment results.\u3cbr/\u3

Treatment delineation impact on Gamma Knife radiosurgical response of vestibular schwannoma

Prognostic factors of tumor control after Gamma Knife radiosurgery for vestibular schwannomas (VS) are largely unknown. This paper attempts to establish an explanation for tumor response by exploring the possible relation between the accuracy of tumor delineation by physicians and the tumor response derived from an imaging database. This relationship has not yet been reported. To this end, we measure the differences between the treatment delineation and a delineation by the specialist using the following metrics: tumor volumes, number of slices, slice area and slice similarity. By observing data from 40 patients, comprising of 20 successfully and 20 unsuccessfully treated patients, we find that there is no evidence that a less accurate delineation leads to a higher failure rate. The results even show the opposite: the delineation of the successful group is less accurate than the delineation of the unsuccessful group, when the treatment delineation is\u3cbr/\u3ecompared to a retrospectively created delineation by a VS specialist. This suggests that, within the limitation of this research and experiment so far, the more difficult it is to delineate the tumor during treatment planning, the more likely it is to achieve treatment success

Dose distribution as outcome predictor for Gamma Knife radiosurgery on vestibular schwannoma

Vestibular schwannomas are benign brain tumors that can be treated radiosurgically with the Gamma Knife in order to stop tumor progression. However, in some cases tumor progression is not stopped and treatment is deemed a failure. At present, the reason for these failed treatments is unknown. Clinical factors and MRI characteristics have been considered as prognostic factors. Another confounder in the success of treatment is the treatment planning itself. It is thought to be very uniformly planned, even though dose distributions among treatment plans are highly inhomogeneous. This paper explores the predictive value of these dose distributions for the treatment outcome. We compute homogeneity indices (HI) and three-dimensional histogram-of-oriented gradients (3D-HOG) and employ support vector machine (SVM) paired with principal component analysis (PCA) for classification. In a clinical dataset, consisting of 20 tumors that showed treatment failure and 20 tumors showing treatment success, we discover that the correlation of the HI values with the treatment outcome presents no statistical evidence of an association (52:5% accuracy employing linear SVM and no statistical significant difference with t-tests), whereas the 3D-HOG features concerning the dose distribution do present correlations to the treatment outcome, suggesting the influence of the treatment on the outcome itself (77:5% accuracy employing linear SVM and PCA). These findings can provide a basis for refining towards personalized treatments and prediction of treatment efficiency. However, larger datasets are needed for more extensive analysis

Prediction of transient tumor enlargement using MRI tumor texture after radiosurgery on vestibular schwannoma

\u3cp\u3ePurpose: Vestibular schwannomas (VSs) are uncommon benign brain tumors, generally treated using Gamma Knife radiosurgery (GKRS). However, due to the possible adverse effect of transient tumor enlargement (TTE), large VS tumors are often surgically removed instead of treated radiosurgically. Since microsurgery is highly invasive and results in a significant increased risk of complications, GKRS is generally preferred. Therefore, prediction of TTE for large VS tumors can improve overall VS treatment and enable physicians to select the most optimal treatment strategy on an individual basis. Currently, there are no clinical factors known to be predictive for TTE. In this research, we aim at predicting TTE following GKRS using texture features extracted from MRI scans. Methods: We analyzed clinical data of patients with VSs treated at our Gamma Knife center. The data was collected prospectively and included patient- and treatment-related characteristics and MRI scans obtained at day of treatment and at follow-up visits, 6, 12, 24 and 36 months after treatment. The correlations of the patient- and treatment-related characteristics to TTE were investigated using statistical tests. From the treatment scans, we extracted the following MRI image features: first-order statistics, Minkowski functionals (MFs), and three-dimensional gray-level co-occurrence matrices (GLCMs). These features were applied in a machine learning environment for classification of TTE, using support vector machines. Results: In a clinical data set, containing 61 patients presenting obvious non-TTE and 38 patients presenting obvious TTE, we determined that patient- and treatment-related characteristics do not show any correlation to TTE. Furthermore, first-order statistical MRI features and MFs did not significantly show prognostic values using support vector machine classification. However, utilizing a set of 4 GLCM features, we achieved a sensitivity of 0.82 and a specificity of 0.69, showing their prognostic value of TTE. Moreover, these results increased for larger tumor volumes obtaining a sensitivity of 0.77 and a specificity of 0.89 for tumors larger than 6 cm \u3csup\u3e3\u3c/sup\u3e. Conclusions: The results found in this research clearly show that MRI tumor texture provides information that can be employed for predicting TTE. This can form a basis for individual VS treatment selection, further improving overall treatment results. Particularly in patients with large VSs, where the phenomenon of TTE is most relevant and our predictive model performs best, these findings can be implemented in a clinical workflow such that for each patient, the most optimal treatment strategy can be determined. \u3c/p\u3

Temporal evolution of NMDA-induced excitoxicity in the neonatal rat brain as measured with 1H Nuclear Magnetic Resonance Imaging

The aim of this study is to characterize the evolution of excitotoxic damage in neonatal rat brain by diffusion-weighted and T2-weighted magnetic resonance imaging. Results are compared with histological findings. Magnetic resonance imaging was performed at various times (15 min, 24 h, 3 days and 5 days) after intrastriatal microinjection of N-methyl-d-aspartate (NMDA) at postnatal day 8. The transverse relaxation time (T2) and apparent diffusion coefficient of water were determined. The results show an acute reduction of the apparent diffusion coefficient, reflected by an ipsilateral hyperintensity in the diffusion-weighted images, within 15 min after intrastriatal NMDA injection. At this time no changes in the T2-weighted images were apparent. The volume of the hyperintensity was relatively large with a radius of approximately 2 mm and coincided with histological signs of pronounced karyo-dendritic swelling. Subcutaneous administration of MK-801 25 min after the intracerebral NMDA injection readily reversed the hyperintensity and resulted in complete protection as verified by histology. Areas with increased T2 values were observed 1 day after NMDA microinjection and corresponded to regions with obvious cell necrosis. Five days after NMDA injection the lesion was evident using both diffusion- and T2-weighted images and coincided with an overt lesion comprising areas of cell loss and dilatation of the ipsilateral ventricle. In conclusion, this study illustrates the possibility of using diffusion-weighted imaging as a tool to monitor efficacy of treatment strategies at an early stage of excitotoxic injury

Correlation between pre-treatment growth rate and tumor control of vestibular schwannomas after gamma knife radiosurgery in the dutch database

Introduction: Prognostic factors of tumor control after Gamma Knife Radiosurgery (GKRS) for vestibular schwannoma (VS) are largely unknown. Recently, it has been reported that the growth rate of VS before treatment is indicative of the chance that radiosurgery achieves tumor control. Such findings may have important implications for treatment strategies and may lead to advise for either microsurgery or higher marginal doses for fast growing tumors. However, studies on this important aspect are limited and show conflicting results. Moreover, the available studies are hampered by methodological limitations such as limited patient numbers and followup and two-dimensional assessment of tumor size. The objective of this study is to identify a possible correlation between pre-treatment growth rate and tumor control after GKRS in a large database with sufficient follow-up and volumetric tumor assessments.\u3cbr/\u3eMethods: In the prospectively collected database of the Gamma Knife Center Tilburg, 445 patients with VS, treated between 2002 and 2014, that showed documented growth before treatment and who have had a minimum follow-up of 2 years after treatment, were identified. Tumor volumes before, at and after treatment were assessed. GKRS was performed in a uniform way, with a dose of 12-13Gy prescribed to the isodose line covering 90-99% of the target. Failures were defined as tumor progression on 2 consecutive MRI’s beyond 2 years after GKRS, or as judged by the radiosurgical team. Volume doubling times (VDT) before treatment were correlated with the observed tumor control rates and volumetric responses after treatment. \u3cbr/\u3eResults: Until now 266 of the 445 patients with documented pre-treatment tumor growth have been analyzed. 25 Patients were lost to follow-up. The median follow-up was 4 years. 25 Patients showed a radiological failure. The 5- and 10-year actuarial control rates were 91% and 78% respectively. VDT varied from 3 to 344 months, with a median of 16 months. Using the Mann-Whitney-U test, the VDT of tumors that showed tumor control is significantly higher than those that failed (p=0.01). After stratifying for VDT at the median, slow growing tumors showed a 5- and 10-year actuarial control rate of 97% and 89%, where the fast growing tumors had a 5- and 10-year control rate of 85% and 68% (p=0.009).\u3cbr/\u3eConclusion: This study clearly shows that the pretreatment growth rate correlates with the observed tumor control after GKRS. Fast growing tumors are less likely to show tumor control. This finding might justify alterations in the management of VS

Effect of a web-based audit and feedback intervention with outreach visits on the clinical performance of multidisciplinary teams: a cluster-randomized trial in cardiac rehabilitation

BACKGROUND: The objective of this study was to assess the effect of a web-based audit and feedback (A&amp;F) intervention with outreach visits to support decision-making by multidisciplinary teams.METHODS: We performed a multicentre cluster-randomized trial within the field of comprehensive cardiac rehabilitation (CR) in the Netherlands. Our participants were multidisciplinary teams in Dutch CR centres who were enrolled in the study between July 2012 and December 2013 and received the intervention for at least 1 year. The intervention included web-based A&amp;F with feedback on clinical performance, facilities for goal setting and action planning, and educational outreach visits. Teams were randomized either to receive feedback that was limited to psychosocial rehabilitation (study group A) or to physical rehabilitation (study group B). The main outcome measure was the difference in performance between study groups in 11 care processes and six patient outcomes, measured at patient level. Secondary outcomes included effects on guideline concordance for the four main CR therapies.RESULTS: Data from 18 centres (14,847 patients) were analysed, of which 12 centres (9353 patients) were assigned to group A and six (5494 patients) to group B. During the intervention, a total of 233 quality improvement goals was identified by participating teams, of which 49 (21%) were achieved during the study period. Except for a modest improvement in data completeness (4.5% improvement per year; 95% CI 0.65 to 8.36), we found no effect of our intervention on any of our primary or secondary outcome measures.CONCLUSIONS: Within a multidisciplinary setting, our web-based A&amp;F intervention engaged teams to define local performance improvement goals but failed to support them in actually completing the improvement actions that were needed to achieve those goals. Future research should focus on improving the actionability of feedback on clinical performance and on addressing the socio-technical perspective of the implementation process.TRIAL REGISTRATION: NTR3251.</p