Evaluation of tumor heterogeneity based on texture parameters has recently attracted much interest in the PET imaging community. However, the impact of reconstruction settings on texture parameters is unclear, especially relating to time-offlight and point-spread function modeling. Their effects on 55 texture features (TFs) and 6 features based on first-order statistics (FOS) were investigated. Standardized uptake value (SUV) measures were also evaluated as peak SUV (SUV peak ), maximum SUV, and mean SUV (SUV mean ). Methods: This study retrospectively recruited 20 patients with lesions in the lung who underwent whole-body 18 F-FDG PET/CT. The coefficient of variation (COV) of each feature across different reconstructions was calculated. Results: SUV peak , SUV mean , 18 TFs, and 1 FOS were the most robust (COV # 5%) whereas skewness, cluster shade, and zone percentage were the least robust (COV . 20%) with respect to reconstruction algorithms using default settings. Heterogeneity parameters had different sensitivities to iteration number. Twenty-four parameters including SUV peak and SUV mean exhibited variation with a COV less than 5%; 28 parameters, including maximum SUV, showed variation with a COV in the range of 5%-10%. In addition, skewness, cluster shade, and zone percentage were the most sensitive to iteration number. In terms of sensitivity to full width at half maximum (FWHM), 15 TFs and 1 FOS had the best performance with a COV less than 5%, whereas SUV peak and SUV mean had a COV between 5% and 10%. Grid size had the largest impact on image features, which was demonstrated by only 11 features, including SUV peak and SUV mean , having a COV less than 10%. Conclusion: Different image features have different sensitivities to reconstruction settings. Iteration number and FWHM of the gaussian filter have a similar impact on the image features. Grid size has a larger impact on the features than iteration number and FWHM. The features that exhibited large variations such as skewness in FOS, cluster shade, and zone percentage should be used with caution. The entropy in FOS, difference entropy, inverse difference normalized, inverse difference moment normalized, low gray-level run emphasis, high gray-level run emphasis, and low gray-level zone emphasis are the most robust features.

No abstract

NCT01184807.

BackgroundRegorafenib, a multi-kinase inhibitor, is used in the treatment of patients with metastatic colorectal cancer refractory to standard therapy. However, this benefit was limited to 1.4 months improvement in overall survival, with more than half of patients experiencing grade 3 to 4 adverse events. We aim to elucidate the pharmacodynamic effects of regorafenib in metastatic colorectal cancer and discover potential biomarkers that may predict clinical benefit.MethodsPatients with metastatic colorectal adenocarcinoma refractory to standard therapy with tumours amenable to biopsy were eligible for the study. Regorafenib was administered orally at 160 mg daily for 3 out of 4 weeks with tumour assessment every 2 cycles. Metabolic response was assessed by FDG PET-CT scans (pre-treatment and day 15); paired tumour biopsies (pre-treatment and day 21 post-treatment) were sampled for immunohistochemistry and proteomic profiling analyses. Plasma circulating cell free DNA was quantified serially before and after treatment.ResultsThere were 2(6%) partial responses out of 35 patients, and 8(23%) patients had stable disease for more than 7 months. Adverse event profile was similar to reported data. Recurrent somatic mutations in K-RAS, PIK3CA and BRAF were detected in plasma circulating cell free DNA in 14 patients; some mutations were not found in archival tumour. Total plasma circulating cell free DNA inversely correlated with progression free survival (PFS), and presence of KRAS mutations associated with shorter PFS. Immunohistochemistry of pre- and post- treatment biopsies showed majority of patients had downregulation of phosphorylated-VEGFR2, podoplanin, phosphorylated-AKT, Ki-67 and upregulation of the MEK-ERK axis, phosphorylated-C-MET, phosphorylated-SRC, phosphorylated-STAT3 and phosphorylated-JUN. Proteomic analysis of fine needle tumour aspirates showed down-regulation of PI3K was associated with longer PFS.ConclusionPlasma circulating cell free DNA may yield potential predictive biomarkers of regorafenib treatment. Downregulation of the PI3K-AKT axis may be an important predictor of clinical benefit.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0405-4) contains supplementary material, which is available to authorized users.

Tc HMPAO) SPECT. STA-MCA bypass surgery was offered to patients with impaired CVR on SPECT. All patients underwent TCD and SPECT at 4 ± 1 months and were followed up for cerebral ischemic events. results A total of 112 patients were included. This total included 73 men, and the mean age of the entire study population was 56 years (range 23-78 years). 99mTc HMPAO SPECT demonstrated impaired CVR in 77 patients (69%). Of these 77 patients, 46 underwent STA-MCA bypass while 31 received best medical treatment. TCD and acetazolamidechallenge 99m Tc HMPAO SPECT repeated at 4 ± 1 months showed significant improvement in the STA-MCA bypass group. During a mean follow-up of 34 months (range 18-39 months), only 6 (13%) of 46 patients in the bypass group developed cerebral ischemic events, as compared with 14 (45%) of 31 patients receiving medical therapy (absolute risk reduction 32%, p = 0.008). coNclusioNs STA-MCA bypass surgery in carefully selected patients with symptomatic severe intracranial stenoocclusive disease of the intracranial ICA or MCA results in significant improvement in hemodynamic parameters and reduction in stroke recurrence.http://thejns.org/doi/abs/10.3171/2014.11.JNS141553KeY words acute ischemic stroke; intracranial atherosclerosis; cerebral vasodilatory reserve; SPECT; external carotid-internal carotid bypass; superficial temporal artery; middle cerebral artery; bypass; vascular disorders 662©AANS, 2015 ec-ic bypass for intracranial stenosis