Inter-observer reproducibility of quantitative dynamic susceptibility contrast and diffusion MRI parameters in histogram analysis of gliomas

Background Dynamic-susceptibility contrast and diffusion-weighted imaging are promising techniques in diagnosing glioma grade. Purpose To compare the inter-observer reproducibility of multiple dynamic-susceptibility contrast and diffusion-weighted imaging parameters and to assess their potential in differentiating low- and high-grade gliomas. Material and Methods Thirty patients (16 men; mean age = 40.6 years) with low-grade (n = 13) and high-grade (n = 17) gliomas and known pathology, scanned with dynamic-susceptibility contrast and diffusion-weighted imaging were included retrospectively between March 2006 and March 2014. Three observers used three different methods to define the regions of interest: (i) circles at maximum perfusion and minimum apparent diffusion coefficient; (ii) freeform 2D encompassing the tumor at largest cross-section only; (iii) freeform 3D on all cross-sections. The dynamic-susceptibility contrast curve was analyzed voxelwise: maximum contrast enhancement; time-to-peak; wash-in rate; wash-out rate; and relative cerebral blood volume. The mean was calculated for all regions of interest. For 2D and 3D methods, histogram analysis yielded additional statistics: the minimum and maximum 5% and 10% pixel values of the tumor (min5%, min10%, max5%, max10%). Intraclass correlations coefficients (ICC) were calculated between observers. Low- and high-grade tumors were compared with independent t-tests or Mann-Whitney tests. Results ICCs were highest for 3D freeform (ICC = 0.836-0.986) followed by 2D freeform (ICC = 0.854-0.974) and circular regions of interest (0.141-0.641). High ICC and significant discrimination between low- and high-grade gliomas was found for the following optimized parameters: apparent diffusion coefficient (P <0.001; ICC = 0.641; mean; circle); time-to-peak (P = 0.015; ICC = 0.986; mean; 3D); wash-in rate (P = 0.004; ICC = 0.826; min10%; 3D); wash-out rate (P <0.001; ICC = 0.860; min10%; 2D); and relative cerebral blood volume (

Functional MRI for Treatment Evaluation in Patients with Head and Neck Squamous Cell Carcinoma:A Review of the Literature from a Radiologist Perspective

Purpose of review: To show the role of functional MRI in patients treated for head and neck squamous cell carcinoma. Recent findings: MRI is commonly used for treatment evaluation in patients with head and neck tumors. However, anatomical MRI has its limits in differentiating between post-treatment effects and tumor recurrence. Recent studies showed promising results of functional MRI for response evaluation. Summary: This review analyzes possibilities and limitations of functional MRI sequences separately to obtain insight in the post-therapy setting. Diffusion, perfusion and spectroscopy show promise, especially when utilized complimentary to each other. These functional MRI sequences aid in the early detection which might improve survival by increasing effectiveness of salvage therapy. Future multicenter longitudinal prospective studies are needed to provide standardized guidelines for the use of functional MRI in daily clinical practice

Cerebral vasculitis, a diagnostic labyrinth

A diagnosis of cerebral vasculitis is frequently considered in patients with new or progressive neurological symptoms for which there is no other explanation. A clinician considering a diagnosis of cerebral vasculitis should be well aware of alternative diagnoses, since these are generally more common. Several consecutive examinations are required for diagnosing cerebral vasculitis, because there is no diagnostic procedure that is highly sensitive as well as highly specific. The added value of the different procedures may depend on the type of blood vessels involved. Standard MRI examinations are sensitive but not specific. Special MRI techniques now make it also possible to make images of the vessel wall itself. Catheter angiography remains important, especially when noninvasive angiographic techniques do not reveal any abnormalities. Brain biopsy can provide proof of cerebral vasculitis and also serves to exclude mimicking conditions.</p

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with head and neck tumors, a systematic review and meta-analysis

Background Novel advanced MRI techniques are investigated in patients treated for head and neck tumors as conventional anatomical MRI is unreliable to differentiate tumor from treatment related imaging changes. Purpose As the diagnostic accuracy of MRI techniques to detect tumor residual or recurrence during or after treatment is variable reported in the literature, we performed a systematic metaanalysis. Data sources Pubmed, EMBASE and Web of Science were searched from their first record to September 23 th 2014. Study selection Studies reporting diagnostic accuracy of anatomical, ADC, perfusion or spectroscopy to identify tumor response confirmed by histology or follow-up in treated patients for head and neck tumors were selected by two authors independently. Data analysis Two authors independently performed data extraction including true positives, false positives, true negatives, false negatives and general study characteristics. Meta-analysis was performed using bivariate random effect models when >= 5 studies per test were included. Data synthesis We identified 16 relevant studies with anatomical MRI and ADC. No perfusion or spectroscopy studies were identified. Pooled analysis of anatomical MRI of the primary site (11 studies, N = 854) displayed a sensitivity of 84% (95% CI 72-92) and specificity of 82% (71-89). ADC of the primary site (6 studies, N = 287) showed a pooled sensitivity of 89% (74 - 96) and specificity of 86% (69 - 94). Limitations Main limitation are the low, but comparable quality of the included studies and the variability between the studies. Conclusions The higher diagnostic accuracy of ADC values over anatomical MRI for the primary tumor location emphases the relevance to include DWI with ADC for response evaluation of treated head and neck tumor patients

Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type glioblastoma

PURPOSE: (11)C-Methionine ((11)C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for survival correlation in patients with IDH wild type glioblastomas. METHODS: Thirteen IDH wild type glioblastoma patients underwent preoperative (11)C-MET PET. Both SUV-based parameters and volume-based parameters were calculated for each lesion. Kaplan-Meier curves with log-rank testing and Cox regression analysis were used for correlation between PET parameters and overall survival. RESULTS: Median overall survival for the entire cohort was 393 days. MTV (HR 1.136, p = 0.007) and TLMM (HR 1.022, p = 0.030) were inversely correlated with overall survival. SUV-based (11)C-MET PET parameters did not show a correlation with survival. In a paired analysis with other clinical parameters including age and radiotherapy dose, MTV and TLMM were found to be independent factors. CONCLUSIONS: MTV and TLMM, and not SUV, significantly correlate with overall survival in patients with IDH wild type glioblastomas. The incorporation of volume-based (11)C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population

Influence of MRI Follow-Up on Treatment Decisions during Standard Concomitant and Adjuvant Chemotherapy in Patients with Glioblastoma:Is Less More?

MRI is the gold standard for treatment response assessments for glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, a reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy at 2-3 month intervals actually benefits patients and how it influences clinical decision making about the continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans post-chemoradiotherapy (post-CCRT), after three cycles of adjuvant chemotherapy [TMZ3/6], and after the completion of treatment [TMZ6/6]), and of unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in an early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p &lt; 0.001). Perfusion MRI caused less diagnostic uncertainty ( p = 0.021) but did not influence treatment consequences ( p = 0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach. </p

Diagnostic accuracy of positron emission tomography tracers for the differentiation of tumor progression from treatment-related changes in high-grade glioma:a systematic review and meta-analysis

Background: Post-treatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent response assessment in neuro-oncology (RANO) recommendations PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and meta-analysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: Pubmed, Web of Science and Embase were searched systematically. Study selection, data extraction and quality assessment were performed independently by two authors. Meta-analysis was performed using a bivariate random effects model when ≥ 5 studies were included. Results: 39 studies (11 tracers) were included in the systematic review. 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95%CI 72-92) and 84% (69-93), respectively. 18F-FET (7 studies, 172 lesions) demonstrated a sensitivity of 90% (81-95) and specificity of 85% (71-93). 11C-MET (8 studies, 151 lesions) sensitivity was 93% (80-98) and specificity was 82% (68-91). The number of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93-100% and 0-100% for 18F-FLT, 85-100% and 72-100% for 18F-FDOPA and 100% and 70-88% for 11C-CHO, respectively. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparable higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited, thus 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas

PERFECTRA:A pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs

Objective To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. Methods Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) &lt;2.6, changes in PROMs and radiographic progression. Results A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP &lt;2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. Conclusion Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.</p

PERFECTRA:A pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs

Objective To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. Methods Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) &lt;2.6, changes in PROMs and radiographic progression. Results A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP &lt;2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. Conclusion Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.</p

PERFECTRA:A pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs

Objective To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. Methods Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) &lt;2.6, changes in PROMs and radiographic progression. Results A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP &lt;2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. Conclusion Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.</p