Assessment of very early response evaluation with 18F-FDG-PET/CT predicts survival in erlotinib treated NSCLC patients-A comparison of methods.

We evaluated whether changes in 18F-Fluoro-D-Glucose (18F-FDG)-uptake evaluated early during erlotinib treatment predict survival in non-small cell lung cancer (NSCLC) patients. Positron emission tomography (PET)/CT scans from 56 NSCLC patients before and after 7-10 days of erlotinib treatment were analyzed with four different methods: Visual evaluation and percentage change in lean body mass corrected standardized uptake values (SULs): SULpeak, SULmax and total lesion glycolysis (TLG). The semi-quantitative parameters abilities to predict progression free survival (PFS) and overall survival (OS) were compared and we found that percentage change in SULpeak, SULmax and TLG all correlated with PFS and OS with the strongest correlation found for TLG (R=0.51, P < 0.001). The highest area under the curve (AUC) for predicting OS was for TLG (0.70 (0.56-0.85)) with a sensitivity of 0.68 and a specificity of 079. All methods except visual evaluation, SULpeak at 15% and 30%, and TLG at 40% cut-off separates the survival curves for the response categories for PFS. For OS, visual evaluation and SULmax did not, whereas TLG at 4 different cut-off levels and SULpeak at the three lowest cut-off levels did. IN CONCLUSION: Early change in 18F-FDG-uptake during erlotinib correlated to both PFS and OS. TLG, as suggested by PERCIST 1.0, shows the strongest correlation to survival, whereas visual evaluation seems to be less sensitive at this very early time-point, but lower cut-off levels for discriminating between response categories seem to be relevant as we find that 20-25% change for both response and progression is optimal.

18F-FDG PET/CT for Very Early Response Evaluation Predicts CT Response in Erlotinib-Treated Non-Small Cell Lung Cancer Patients: A Comparison of Assessment Methods.

The purpose of this study was to determine which method for early response evaluation with 18F-FDG PET/CT performed most optimally for the prediction of response on a later CT scan in erlotinib-treated non-small cell lung cancer patients. Methods:18F-FDG PET/CT scans were obtained before and after 7-10 d of erlotinib treatment in 50 non-small cell lung cancer patients. The scans were evaluated using a qualitative approach and various semiquantitative methods including percentage change in SUVs, lean body mass-corrected (SUL) SULpeak, SULmax, and total lesion glycolysis (TLG). The PET parameters and their corresponding response categories were compared with the percentage change in the sum of the longest diameter in target lesions and the resulting response categories from a CT scan obtained after 9-11 wk of erlotinib treatment using receiver-operating-characteristic analysis, linear regression, and quadratic-weighted κ. Results: TLG delineation according to the PERCIST showed the strongest correlation to sum of the longest diameter (R = 0.564, P < 0.001), compared with SULmax (R = 0.298, P = 0.039) and SULpeak (R = 0.402, P = 0.005). For predicting progression on CT, receiver-operating-characteristic analysis showed area under the curves between 0.79 and 0.92, with the highest area under the curve of 0.92 (95% confidence interval [CI], 0.84-1.00) found for TLG (PERCIST). Furthermore, the use of a cutoff of 25% change in TLG (PERCIST) for both partial metabolic response and progressive metabolic disease, which is the best predictor of the CT response categories, showed a κ-value of 0.53 (95% CI, 0.31-0.75). This method identifies 41% of the later progressive diseases on CT, with no false-positives. Visual evaluation correctly categorized 50%, with a κ-value of 0.47 (95% CI, 0.24-0.70). Conclusion: TLG (PERCIST) was the optimal predictor of response on later CT scans, outperforming both SULpeak and SULmax The use of TLG (PERCIST) with a 25% cutoff after 1-2 wk of treatment allows us to safely identify 41% of the patients who will not benefit from erlotinib and stop the treatment at this time.

Noninvasive Detection of Cardiac Allograft Vasculopathy by Stress Exercise Echocardiographic Assessment of Myocardial Deformation.

BACKGROUND: The aim of this study was to evaluate the value of noninvasive assessment of cardiac allograft vasculopathy (CAV) in heart-transplanted patients by exercise stress myocardial deformation and coronary flow reserve (CFR) assessment. METHODS: Fifty-eight heart-transplanted patients underwent semisupine exercise echocardiography with assessment of left ventricular (LV) longitudinal myocardial deformation. CAV was assessed by coronary angiography and noninvasive CFR by (15)O-H2O positron emission tomographic imaging and Doppler echocardiography. Patients were divided into three groups on the basis of angiographic CAV: no CAV (n = 21), mild CAV (n = 19), and severe CAV (n = 18). RESULTS: Patients with severe CAV had significantly lower LV global longitudinal strain (GLS) at rest (no CAV, -16 ± 2%; mild CAV, -15 ± 2%; severe CAV, -12 ± 4%; P < .001), failed to increase LV GLS during exercise (no CAV, -5.7 ± 2.0%; mild CAV, -3.3 ± 2.9%; severe CAV, -0.2 ± 2.8%; P < .0001), and had significantly lower echocardiographic coronary flow velocity reserve (CFVR) (no CAV, 3.2 ± 0.4; mild CAV, 2.7 ± 0.7; severe CAV, 1.8 ± 0.5; P < .0001) and PET CFR (no CAV, 3.4 ± 0.9; mild CAV, 3.1 ± 0.9; severe CAV, 1.9 ± 0.8; P < .0001). Furthermore, patients with mild CAV had significantly lower exercise LV GLS and echocardiographic CFVR than patients with no CAV. Exercise LV GLS, echocardiographic CFVR, and PET CFR were significantly correlated with the presence of severe CAV in a logistic regression model (LV GLS odds ratio, 0.71; 95% CI, 0.60-0.84; P < .0001; echocardiographic CFVR odds ratio: 0.06; 95% CI, 0.01-0.23; PET CFR odds ratio, 0.17; 95% CI, 0.07-0.46). This relation remained significant after adjustment for symptoms and time since transplantation. CONCLUSIONS: Noninvasive assessment of LV longitudinal myocardial deformation during exercise is feasible and strongly associated with the presence and degree of CAV. Exercise stress myocardial deformation analysis, echocardiographic CFVR, or PET CFR may serve as a noninvasive model for the detection of CAV.

2nd Combined Working Group and Management Committee Meeting of Urine and Kidney Proteomics COST Action 29-30 March 2009, Nafplio, Greece.

EuroKUP (Urine and Kidney Proteomics; www.eurokup.org) is a COST (European Cooperation in the field of Scientific and Technical research: www.cost.esf.org Action fostering a multi-disciplinary network of investigators from 25 countries and focusing on facilitating translational proteomic research in kidney diseases. Four Working Groups focusing respectively on defining clinically important research questions in kidney diseases, kidney tissue proteomics, urine proteomics and bioinformatics have been generated. The EuroKUP members had their second combined Working Group and Management Committee (MC) meeting in Nafplio, Greece from March 29 to 30, 2009. This report summarizes the main presentations, discussions and agreed action points during this meeting. These refer to the design of collaborative projects and clinical center networks for specific kidney diseases; establishment of guidelines for kidney tissue proteomics analysis by laser-based imaging- and laser capture microdissection-MS; development and characterization of a "standard" urine specimen to be used for assessment of platform capability and data comparability in clinical proteomics applications; definition of statistical requirements in biomarker discovery studies; and development of a specialized kidney and urine ontology. Various training activities are planned involving training schools on laser capture microdissection- and imaging-MS, workshops on ontologies as well as short-term travel grants for junior investigators.

How accurate is dynamic contrast-enhanced MRI in the assessment of renal glomerular filtration rate? A critical appraisal.

PURPOSE: To evaluate the current literature to see if the published results of MRI-glomerular filtration rate (GFR) stand up to the claim that MRI-GFR may be used in clinical practice. Claims in the current literature that Gadolinium (Gd) DTPA dynamic contrast enhanced (DCE) MRI clearance provides a reliable estimate of glomerular filtration are an overoptimistic interpretation of the results obtained. Before calculating absolute GFR from Gd-enhanced MRI, numerous variables must be considered. MATERIALS AND METHODS: We examine the methodology in the published studies on absolute quantification of MRI-GFR. The techniques evaluated included the dose and volume of Gd-DTPA used, the speed of injection, acquisition sequences, orientation of the subject, re-processing, conversion of signal to concentration and the model used for analysis of the data as well as the MRI platform. RESULTS: Claims in the current literature that using DCE MRI "Gd DTPA clearance provides a good estimate of glomerular filtration" are not supported by the data presented and a more accurate conclusion should be that "no MRI approach used provides a wholly satisfactory measure of renal GFR function." CONCLUSION: This study suggests that DCE MRI-GFR results are not yet able to be used as a routine clinical or research tool. The published literature does not show what change in DCE MRI-GFR is clinically significant, nor do the results in the literature allow a single DCE MRI-GFR measurement to be correlated directly with a multiple blood sampling technique.