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1.
Phys Med Biol ; 64(17): 175002, 2019 08 28.
Article in English | MEDLINE | ID: mdl-31344691

ABSTRACT

This study aims at assessing whether EANM harmonisation strategy combined with EQ·PET methodology could be successfully applied to harmonize brain 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) images. The NEMA NU 2 body phantom was prepared according to the EANM guidelines with an [18F]FDG solution. Raw PET phantom data were reconstructed with three different reconstruction protocols frequently used in clinical PET brain imaging: ([Formula: see text]) Ordered subset expectation maximization (OSEM) 3D with time of flight (TOF), 2 iterations and 21 subsets; ([Formula: see text]) OSEM 3D with TOF, 6 iterations and 21 subsets; and ([Formula: see text]) OSEM 3D with TOF, point spread function (PSF), and 8 iterations and 21 subsets. EQ·PET filters were computed as the Gaussian smoothing that best independently aligned the recovery coefficients (RCs) of reconstructions [Formula: see text] and [Formula: see text] with the RCs of the reference reconstruction, [Formula: see text]. The performance of the EQ·PET filter to reduce variations in quantification due to differences in reconstruction was investigated using clinical PET brain images of 35 early-onset Alzheimer's disease (EOAD) patients. Qualitative assessments and multiple quantitative metrics on the cortical surface at different scale levels with or without partial volume effect correction were evaluated on the [18F]FDG brain data before and after application of the EQ·PET filter. The EQ·PET methodology succeeded in finding the optimal smoothing that minimised root-mean-square error (RMSE) calculated using human brain [18F]FDG-PET datasets of EOAD patients, providing harmonized comparisons in the neurological context. Performance was superior for TOF than for TOF + PSF reconstructions. Results showed the capability of the EQ·PET methodology to minimize reconstruction-induced variabilities between brain [18F]FDG-PET images. However, moderate variabilities remained after harmonizing PSF reconstructions with standard non-PSF OSEM reconstructions, suggesting that precautions should be taken when using PSF modelling.


Subject(s)
Brain/diagnostic imaging , Image Processing, Computer-Assisted/methods , Positron-Emission Tomography/methods , Fluorodeoxyglucose F18 , Humans , Image Processing, Computer-Assisted/standards , Phantoms, Imaging , Positron-Emission Tomography/standards , Radiopharmaceuticals
2.
Brain Stimul ; 12(3): 794-796, 2019.
Article in English | MEDLINE | ID: mdl-30772276

ABSTRACT

INTRODUCTION: Psychogenic non-epileptic seizures (PNES) are paroxysms of either altered subjective or objective manifestations that may mimic epileptic seizures (ES), without abnormal neuronal epileptiform activity. In this report, we present the case of a 39-year-old woman with PNES and functional movement disorders, who was successfully treated with neuro-guided transcranial direct current stimulation (tDCS). METHODS: We used a PET-guided tDCS approach, as a hypometabolism of the frontal region was revealed by FDG TEP scan. TDCs was performed 5 days/week, 2 times/day, during 3 weeks. All clinical manifestations were reported in a seizure diary. We also assessed dissociation, depression, alexithymia, psychotraumatic scales, and involuntary movements. RESULTS: The treatment was followed by a decrease of both psychogenic involuntary movements and PNES at 5 weeks. At the same time, PTSD symptoms, dissociative symptoms, depression and alexithymia improved. CONCLUSION: PET-scan and tDCS seems to be promising tools for the evaluation and treatment of PNES in clinical practice, and may have a specific role on dissociative symptoms.


Subject(s)
Seizures/therapy , Transcranial Direct Current Stimulation/methods , Adult , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Humans , Positron-Emission Tomography/methods
3.
Clin Nucl Med ; 44(2): 127-129, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30516676

ABSTRACT

We report the case of a 31-year-old woman with left foot bones located epithelioid hemangioendothelioma. It is a rare type of vascular tumor, locally aggressive with metastatic potential. It was revealed by a chronic isolated left foot pain. Conventional imaging showed multiple osteolytic lesions of the bones, appearing aggressive. Both bone scintigraphy and F-FDG PET showed an increased uptake of these lesions and confirmed the limited extent to distal extremity of the left lower limb. Final diagnosis was given on a surgical biopsy. Patient was treated by hyperthermic chemotherapy using isolated limb perfusion.


Subject(s)
Fluorodeoxyglucose F18 , Foot Bones/diagnostic imaging , Hemangioendothelioma, Epithelioid/diagnostic imaging , Positron-Emission Tomography , Adult , Female , Hemangioendothelioma, Epithelioid/pathology , Humans
4.
Clin Nucl Med ; 44(2): 133-136, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30516677

ABSTRACT

A 57-year-old man was referred to our institution for F-fluorocholine PET/CT to characterize a pulmonary nodule in a context of hepatocellular carcinoma. F-FDG PET/CT did not show any uptake of the pulmonary nodule. F-fluorocholine PET/CT showed high uptake of the pulmonary nodule, confirming its metastatic origin. Furthermore, liver early dynamic acquisitions allowed better visualization of the hepatocellular carcinoma during the "arterial phase" than at equilibrium.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Choline/analogs & derivatives , Hepatic Artery/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography , Biological Transport , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Choline/metabolism , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Male , Middle Aged
5.
Eur Radiol ; 28(12): 5100-5110, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29846802

ABSTRACT

OBJECTIVES: To evaluate the concordance between DECT perfusion and ventilation/perfusion (V/Q) scintigraphy in diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Eighty patients underwent V/Q scintigraphy and DECT perfusion on a 2nd- and 3rd-generation dual-source CT system. The imaging criteria for diagnosing CTEPH relied on at least one segmental triangular perfusion defect on DECT perfusion studies and V/Q mismatch on scintigraphy examinations. RESULTS: Based on multidisciplinary expert decisions that did not include DECT perfusion, 36 patients were diagnosed with CTEPH and 44 patients with other aetiologies of PH. On DECT perfusion studies, there were 35 true positives, 6 false positives and 1 false negative (sensitivity 0.97, specificity 0.86, PPV 0.85, NPV 0.97). On V/Q scans, there were 35 true positives and 1 false negative (sensitivity 0.97, specificity 1, PPV 1, NPV 0.98). There was excellent agreement between CT perfusion and scintigraphy in diagnosing CTEPH (kappa value 0.80). Combined information from DECT perfusion and CT angiographic images enabled correct reclassification of the 6 false positives and the unique false negative case of DECT perfusion. CONCLUSION: There is excellent agreement between DECT perfusion and V/Q scintigraphy in diagnosing CTEPH. The diagnostic accuracy of DECT perfusion is reinforced by the morpho-functional analysis of data sets. KEY POINTS: • Chronic thromboembolic pulmonary hypertension (CTEPH) is potentially curable by surgery. • The triage of patients with pulmonary hypertension currently relies on scintigraphy. • Dual-energy CT (DECT) can provide standard diagnostic information and lung perfusion from a single acquisition. • There is excellent agreement between DECT perfusion and scintigraphy in separating CTEPH and non-CTEPH patients.


Subject(s)
Hypertension, Pulmonary/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Tomography, X-Ray Computed/methods , Ventilation-Perfusion Scan/methods , Adult , Aged , Aged, 80 and over , Chronic Disease , Computed Tomography Angiography/methods , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Perfusion Imaging/methods , Reproducibility of Results , Sensitivity and Specificity , Ventilation-Perfusion Ratio , Young Adult
6.
Eur J Cancer ; 96: 64-72, 2018 06.
Article in English | MEDLINE | ID: mdl-29677642

ABSTRACT

BACKGROUND: In 30% of patients with brain metastasis (BM), neurological symptoms are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). Here, we define the diagnostic value of 18F-fluordesoxyglucose positron emission tomography (FDG-PET/CT) in the workup of BM-CUPS. METHODS: We screened 565 patients operated for BM at the University Hospital Zurich and identified 64 patients with BM-CUPS with data on both FDG-PET/CT and contrast-enhanced chest/abdomen computed tomography (CT) available at BM diagnosis. A cohort of 125 patients with BM-CUPS from Lille and Vienna was used for validation. RESULTS: FDG-PET/CT was not superior to chest/abdomen CT in localising the primary lesion in the discovery cohort, presumably because most primary tumours were lung cancers. However, FDG-PET/CT identified additional lesions suspicious of extracranial metastases in 27 of 64 patients (42%). The inclusion of FDG-PET/CT findings shifted the graded prognostic assessment (GPA) score from 3 with CT alone to 2.5 for PET/CT (p = 3.8 × 10-5, Wilcoxon's test), resulting in a predicted survival of 5.3 versus 3.8 months (p = 6.1 × 10-5; Wilcoxon's test). All observations were confirmed in the validation cohort. CONCLUSIONS: Lung cancers are the most common primary tumour in BM-CUPS; accordingly, CT alone shows similar overall sensitivity for detecting the primary tumour as FDG-PET/CT. Yet, FDG-PET/CT improves the accuracy of staging by detecting more metastases, reflected by decreased GPA scores and decreased predicted survival. Therefore, randomised trials on patients with BM should standardise methods of staging, notably when stratifying for GPA.


Subject(s)
Brain Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18/administration & dosage , Neoplasms, Unknown Primary/diagnostic imaging , Radiopharmaceuticals/administration & dosage , Adult , Aged , Aged, 80 and over , Austria , Brain Neoplasms/mortality , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Female , France , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasms, Unknown Primary/mortality , Neoplasms, Unknown Primary/pathology , Neoplasms, Unknown Primary/therapy , Positron Emission Tomography Computed Tomography , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Switzerland
7.
Neurobiol Aging ; 59: 184-196, 2017 11.
Article in English | MEDLINE | ID: mdl-28882421

ABSTRACT

Until now, hypometabolic patterns and their correlations with neuropsychological performance have not been assessed as a function of the various presentations of sporadic early-onset Alzheimer's disease (EOAD). Here, we processed and analyzed the patients' metabolic maps at the vertex and voxel levels by using a nonparametric, permutation method that also regressed out the effects of cortical thickness and gray matter volume, respectively. The hypometabolism patterns in several areas of the brain were significantly correlated with the clinical manifestations. These areas included the paralimbic regions for typical presentations of sporadic EOAD. For atypical presentations, the hypometabolic regions included Broca's and Wernicke's areas and the pulvinar in language forms, bilateral primary and higher processing visual regions (with right predominance) in visuospatial forms, and the bilateral prefrontal cortex in executive forms. Similar hypometabolism patterns were also observed in a correlation analysis of the 18F-FDG PET data versus domain-specific, neuropsychological test scores. These heterogeneities might reflect different underlying pathophysiological processes in particular clinical presentations of sporadic EOAD and should be taken into account in future longitudinal and therapeutic studies.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Cognition , Positron-Emission Tomography , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Atrophy , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Female , Fluorodeoxyglucose F18 , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Male , Middle Aged , Neuropsychological Tests , Organ Size , Radiopharmaceuticals
8.
Int J Cardiol ; 245: 190-195, 2017 Oct 15.
Article in English | MEDLINE | ID: mdl-28768580

ABSTRACT

BACKGROUND: Right ventricular (RV) systolic function is a powerful prognostic factor in patients with systolic heart failure. The accurate estimation of RV function remains difficult. The aim of the study was to determine the diagnostic accuracy of 2D-speckle tracking RV strain in patients with systolic heart failure, analyzing both free and posterolateral walls. METHODS: Seventy-six patients with dilated cardiopathy (left ventricular end-diastolic volume≥75ml/m2) and left ventricular ejection fraction≤45% had an analysis of the RV strain. Feasibility, reproducibility and diagnostic accuracy of RV strain were analyzed and compared to other echocardiographic parameters of RV function. RV dysfunction was defined as a RV ejection fraction≤40% measured by radionuclide angiography. RESULTS: RV strain feasibility was 93.9% for the free-wall and 79.8% for the posterolateral wall. RV strain reproducibility was good (intra-observer and inter-observer bias and limits of agreement of 0.16±1.2% [-2.2-2.5] and 0.84±2.4 [-5.5-3.8], respectively). Patients with left heart failure have a RV systolic dysfunction that can be unmasked by advanced echocardiographic imaging: mean RV strain was -21±5.7% in patients without RV dysfunction and -15.8±5.1% in patients with RV dysfunction (p=0.0001). Mean RV strain showed the highest diagnostic accuracy to predict depressed RVEF (area under the curve (AUC) 0.75) with moderate sensitivity (60.5%) but high specificity (87.5%) using a cutoff value of -16%. CONCLUSIONS: RV strain seems to be a promising and more efficient measure than previous RV echocardiographic parameters for the diagnosis of RV systolic dysfunction.


Subject(s)
Echocardiography/methods , Heart Failure, Systolic/diagnostic imaging , Heart Failure, Systolic/physiopathology , Radionuclide Angiography/methods , Ventricular Function, Right/physiology , Adult , Female , Humans , Male , Middle Aged , Stroke Volume/physiology , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/physiopathology
9.
Clin Nucl Med ; 42(2): 112-113, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27879491

ABSTRACT

A 58-year-old paraplegic patient was prescribed F-FDG for persistent inflammatory syndrome after aortic surgery for dissection. The examination was performed on a Siemens mCT Flow PET/CT and shows a moderate prostate uptake, related to prostatitis on self-catheterization and a focal renal cortical hypermetabolism of the left medial midpole of a horseshoe kidney, which corresponds to renal parenchyma on the CT, and suggests pyelonephritis, confirmed by Tc-DMSA SPECT/CT.


Subject(s)
Fused Kidney/diagnostic imaging , Positron Emission Tomography Computed Tomography , Pyelonephritis/diagnostic imaging , Fluorodeoxyglucose F18 , Fused Kidney/complications , Humans , Male , Middle Aged , Pyelonephritis/complications , Radiopharmaceuticals , Single Photon Emission Computed Tomography Computed Tomography , Technetium Tc 99m Dimercaptosuccinic Acid
11.
Brain ; 138(Pt 5): 1271-83, 2015 May.
Article in English | MEDLINE | ID: mdl-25805645

ABSTRACT

After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders.


Subject(s)
Dopamine Plasma Membrane Transport Proteins/genetics , Genetic Predisposition to Disease/genetics , Parkinson Disease/genetics , Polymorphism, Genetic/genetics , Aged , Catechol O-Methyltransferase , Dopamine/metabolism , Double-Blind Method , Genotype , Humans , Levodopa/therapeutic use , Middle Aged , Parkinson Disease/drug therapy
12.
Eur J Radiol ; 84(1): 163-171, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25439009

ABSTRACT

BACKGROUND: Because of growing body of interest on the association between fibrosing idiopathic interstitial pneumonias (f-IIP) and ischaemic heart disease, we initiated this prospective study to evaluate the prevalence of asymptomatic coronary artery disease (CAD) in patients with f-IIP. METHODS: Forty-two patients with f-IIP underwent noninvasive screening for CAD that included (a) a chest CT examination enabling calculation of the coronary artery calcium (CAC) score, then depiction of coronary artery stenosis; and (b) stress myocardial perfusion scintigraphy (MPS). Patients with significant coronary abnormalities, defined by a CAC score >400 or coronary artery stenosis >50% at CT and/or perfusion defect >5% at MPS, were referred to the cardiologist. Coronary angiography was indicated in presence of a perfusion defect >10% at MPS or significant left main or proximal left anterior descending stenosis whatever MPS findings. RESULTS: Combining CT and MPS, significant abnormalities were detected in 32/42 patients (76%). The cardiologist: (a) did not consider further investigation in 21 patients (CT abnormalities but no ischaemia at MPS: 12/21; false-positive findings at MPS: 3/21; poor respiratory condition: 6/21); (b) proceeded to coronary angiography in 11 patients which confirmed significant stenoses in 5 patients (5/42; 12%). In the worst-case-scenario (i.e., inclusion of 6 patients with significant coronary artery abnormalities who were not investigated due to poor respiratory condition), the prevalence of CAD reached 26% (11/42). CONCLUSION: In the studied population of patients with f-IIP, asymptomatic CAD ranged between 12% and 26%.


Subject(s)
Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Idiopathic Interstitial Pneumonias/epidemiology , Aged , Comorbidity , Coronary Angiography/methods , Coronary Stenosis/complications , Coronary Stenosis/diagnostic imaging , Female , Humans , Male , Prevalence , Prospective Studies , Tomography, X-Ray Computed/methods
13.
Nucl Med Commun ; 35(9): 908-15, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24785008

ABSTRACT

INTRODUCTION: The prognostic value of standardized uptake values (SUVs) at initiation of and during chemotherapy remains controversial in lung cancer patients. However, metabolic volume (MV) and total lesion glycolysis (TLG) have shown promise in lung cancer stratification before treatment. Our aim was to define the prognostic value of MV and TLG in a homogenous group of advanced-stage lung cancer patients treated with bevacizumab and paclitaxel. MATERIALS AND METHODS: Fifty (18)F-fluorodeoxyglucose PET-computed tomography examinations were studied. SUV, MV and TLG were measured for each detectable lesion (classified as primary tumour, node or distant metastasis). MV values were added to compute tumour MV (MVt), nodal MV (MVn), metastatic MV (MVm) and whole-body MV (MVwb). TLGt, TLGn, TLGm and TLGwb were computed using the same method. Maximal SUVt, SUVn, SUVm and SUVwb were measured. Patients were stratified according to each parameter. Overall survival was compared between parameter-stratified groups using the log rank test. RESULTS: At initiation of bevacizumab and paclitaxel therapy (n=12), only TLGwb and TLGn had strong prognostic value with hazard ratios (HRs) of 11.8 and 5.6, respectively (P<0.03). During treatment with bevacizumab and paclitaxel (n=38), SUVwb (HR: 4.9), MVwb (HR: 4.9), TLGwb (HR: 8.9), SUVt (HR: 15.1), MVt (HR: 15.6) and TLGt (HR: 15.6) had significant prognostic value (P<0.05). Metastasis measurements showed no significant prognostic value. CONCLUSION: MV and TLG are powerful prognostic factors in advanced-stage lung adenocarcinoma being treated with chemotherapy. Focusing on the intrathoracic primary tumour increases the prognostic value of PET in these patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Fluorodeoxyglucose F18 , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Positron-Emission Tomography/methods , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Female , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Image Interpretation, Computer-Assisted/methods , Lung Neoplasms/metabolism , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis , Male , Middle Aged , Paclitaxel/administration & dosage , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Treatment Outcome , Tumor Burden/drug effects
15.
Ann Surg ; 258(1): 66-76, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23470576

ABSTRACT

OBJECTIVE: To evaluate the role of ¹8F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of tumor response after the completion of neoadjuvant chemoradiation (CRT) in patients with locally advanced resectable esophageal cancer. BACKGROUND: After primary CRT, a noninvasive evaluation of the tumor response could help in the treatment decision to identify patients who may benefit from surgery. Whether FDG-PET provides clinically relevant information remains questionable. METHODS: Operable patients with locally advanced esophageal cancer (clinically staged T3 N0-1 M0) were enrolled in this prospective study. The complete treatment plan included neoadjuvant CRT (cisplatin + 5-fluorouracil/45 Gy) followed 6 to 8 weeks later by a transthoracic en bloc esophagectomy. Morphological evaluation combined with FDG-PET was performed 2 weeks before the start of CRT and 4 to 6 weeks after the completion of CRT. Intratumoral pre- and posttreatment FDG-standardized uptake values (SUV1, SUV2, percentage change) were assessed. These variables were correlated with pathological and morphologic responses and survival. Investigators were blinded to the FDG-PET results unless they revealed metastatic disease. RESULTS: Of 60 total patients, 46 underwent the complete treatment plan (median age: 60.1 years; adenocarcinoma: 25 patients; squamous cell cancer: 21 patients). A major pathological response occurred in 45.7% of patients and was associated with a favorable outcome (P = 0.057). Neoadjuvant CRT led to a significant reduction in intratumoral FDG-uptake (P < 0.001). No significant association was seen between a pathological response (either complete or major) and the FDG-PET results (P > 0.280). The SUV2 value was correlated with a morphological response and the possibility to perform an R0 resection (P < 0.018; receiver operating characteristic curve analysis: SUV2 threshold = 5.5). No significant association was found between metabolic imaging and recurrence or survival. CONCLUSIONS: FDG-PET does not effectively correlate with pathological response and long-term survival in patients with locally advanced esophageal cancer undergoing neoadjuvant CRT followed by surgery. (Registered on the www.e-cancer RECF0350.).


Subject(s)
Chemoradiotherapy , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/therapy , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Radiopharmaceuticals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Data Interpretation, Statistical , Esophageal Neoplasms/pathology , Esophagectomy/methods , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Treatment Outcome
16.
Lung Cancer ; 80(2): 197-202, 2013 May.
Article in English | MEDLINE | ID: mdl-23414642

ABSTRACT

BACKGROUND: Combination of bevacizumab and weekly paclitaxel showed synergitic effects, anti-tumor efficacy and a good toxicity profile for patients with breast cancer but has never been evaluated in non small cell lung cancer (NSCLC). We retrospectively reviewed safety and efficacy of this regimen in metastatic non-squamous NSCLC as fourth-line therapy or beyond. METHODS: Patients were identified from a prospective database. Treatment consisted in paclitaxel 80 mg/m(2) on days 1, 8 and 15 and bevacizumab 15 mg/kg on day 1, every 3 weeks until progression or unacceptable toxicity. RESULTS: Twenty patients were included in this study. Objective response rate at first evaluation was 40% (8/20), confirmed response rate was 15% (3/20) and disease control rate was 75% (15/20). The median progression-free survival and overall survival were 6.4 months (CI95% 4.1-9) and 9.6 months (CI95% 7-19.7). Grade 3-4 adverse events included neutropenia (4/20), onycholysis (2/20) and infection (2/20). One patient died from a bowel perforation and another one died from unknown cause. Prolonged responses were observed in a patient who had received bevacizumab as part of first-line chemotherapy and in another one who harbored an ALK rearrangement. CONCLUSIONS: In our experience, combination of bevacizumab and weekly paclitaxel exhibited acceptable toxicity and had encouraging anti-tumor efficacy as fourth-line treatment or beyond for non-squamous NSCLC patients, supporting further evaluation in larger prospective studies.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Neoplasm Metastasis/drug therapy , Paclitaxel/administration & dosage , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/chemically induced , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Paclitaxel/adverse effects , Prospective Studies
17.
J Neurol Neurosurg Psychiatry ; 84(5): 552-5, 2013 May.
Article in English | MEDLINE | ID: mdl-23077087

ABSTRACT

BACKGROUND: Given that memantine is thought to decrease N-methyl-D-aspartic-acid-related (NMDA) glutamatergic hyperactivity and improve locomotion in rats, we sought to assess the drug's impact on axial symptoms in advanced Parkinson's disease (PD). METHODS: We performed a 90-day, randomised, double-blind, study with two parallel arms: 20 mg/day memantine versus placebo (ClinicalTrials.gov:NCT01108029). The main inclusion criterion was the presence of a severe gait disorder and an abnormal, forward-leaning stance. The following parameters were analysed under standardised conditions before and after acute administration of L-dopa: gait (stride length as primary criterion), the United-Parkinson's-Disease-Rating-Scale (UPDRS) motor score and its axial subscore, the hypertonia and strength of the axial extensors and flexors (isokinetic dynamometer), the Dyskinesia Rating Scale score (DRS) and its axial subscore. RESULTS: Twenty-five patients were included. The memantine and placebo group did not differ significantly in terms of stride length. However, in the memantine group, we observed significantly better results (vs placebo) for the overall UPDRS score (F(1,21)=4.9; p=0.039(-1)) and its axial subscore (F(1,21)=7.2; p=0.014(-1.1)), axial hypertonia, the axial and overall DRS and axial strength. CONCLUSIONS: Memantine treatment was associated with lower axial motor symptom and dyskinesia scores but did not improve gait. These benefits must be confirmed in a broader population of patients.


Subject(s)
Antiparkinson Agents/therapeutic use , Memantine/therapeutic use , Parkinson Disease/drug therapy , Aged , Aged, 80 and over , Antiparkinson Agents/adverse effects , Disability Evaluation , Double-Blind Method , Dyskinesia, Drug-Induced/prevention & control , Female , Gait Disorders, Neurologic/drug therapy , Gait Disorders, Neurologic/etiology , Humans , Levodopa/adverse effects , Levodopa/therapeutic use , Male , Memantine/adverse effects , Middle Aged , Pilot Projects , Sample Size
18.
Lancet Neurol ; 11(7): 589-96, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22658702

ABSTRACT

BACKGROUND: Despite optimum medical management, many patients with Parkinson's disease are incapacitated by gait disorders including freezing of gait. We aimed to assess whether methylphenidate--through its combined action on dopamine and noradrenaline reuptake--would improve gait disorders and freezing of gate in patients with advanced Parkinson's disease without dementia who also received subthalamic nucleus stimulation. METHODS: This multicentre, parallel, double-blind, placebo-controlled, randomised trial was done in 13 movement disorders departments in France between October, 2009, and December, 2011. Eligible patients were younger than 80 years and had Parkinson's disease, severe gait disorders, and freezing of gate despite optimised treatment of motor fluctuations with dopaminergic drugs and subthalamic stimulation. We randomly assigned patients (1:1 with a computer random-number generator in blocks of four) to receive methylphenidate (1 mg/kg per day) or placebo capsules for 90 days. Patients, their carers, study staff, investigators, and data analysts were masked to treatment allocation. To control for confounding effects of levodopa we assessed patients under standardised conditions with an acute levodopa challenge. Our primary outcome was a change in the number of steps during the stand-walk-sit (SWS) test without levodopa. We compared the respective mean numbers of steps at day 90 in the methylphenidate and placebo groups in a covariance analysis and adjusted for baseline differences. This trial is registered with ClinicalTrials.gov, number NCT00914095. FINDINGS: We screened 81 patients and randomly assigned 35 to receive methylphenidate and 34 to receive placebo. 33 patients in the methylphenidate group and 32 patients in the placebo group completed the study. Efficacy outcomes were assessed in the patients who completed the study. Compared with patients in the placebo group (median 33 steps [IQR 26-45]), the patients in the methylphenidate group made fewer steps at 90 days (31 [26-42], F((1, 62))=6·1, p=0·017, adjusted size effect 0·61). Adverse events were analysed in all randomly assigned patients. There were significantly more adverse events in the methylphenidate group compared with placebo. Patients on methylphenidate had a significant increase in heart rate (mean 3·6 [SD 7·2] beats per min) and decrease in weight (mean 2·2 [SD 1·8] kg) compared with the placebo group. INTERPRETATION: Methylphenidate improved gait hypokinesia and freezing in patients with advanced Parkinson's disease receiving subthalamic nucleus stimulation. Methylphenidate represents a therapeutic option in the treatment of gait disorders at the advanced stage of Parkinson's disease. The long term risk-benefit balance should be further studied. FUNDING: French Ministry of Health and Novartis Pharma.


Subject(s)
Deep Brain Stimulation , Dopamine Uptake Inhibitors/therapeutic use , Gait Disorders, Neurologic/therapy , Hypokinesia/therapy , Methylphenidate/therapeutic use , Parkinson Disease/therapy , Aged , Double-Blind Method , Female , France , Gait Disorders, Neurologic/etiology , Humans , Hypokinesia/etiology , Male , Middle Aged , Parkinson Disease/complications , Treatment Outcome
19.
Eur Heart J ; 33(21): 2672-9, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22453651

ABSTRACT

AIMS: Previous studies have demonstrated that the radionuclide right ventricular (RV) ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), and tissue Doppler peak systolic tricuspid annular velocity (STr) were independent predictors of cardiac survival in stable patients with left ventricular systolic dysfunction (LVSD). No study has compared the prognostic value of these three RV parameters. The aim of this study was to compare the prognostic value of RVEF, TAPSE, and STr in a large group of patients with LVSD. METHODS AND RESULTS: We analysed 527 consecutive patients who underwent an extensive prognostic evaluation (clinical data, biological data, radionuclide angiography, echoDopplercardiography, cardiopulmonary exercise test). Tricuspid annular plane systolic excursion and STr were weakly correlated with RVEF (r = 0.20). During a follow-up period of 1268 days (802-1830), there were 121 cardiovascular deaths. Best cut-off values were 37%, 9.7 cm/s, and 18.5 mm for RVEF, STr, and TAPSE, respectively. Right ventricular ejection fraction was a powerful independent predictor of cardiac survival [relative risk (RR): 2.05 (1.29-3.26), P = 0.002]. Peak systolic tricuspid annular velocity added a modest prognostic information [RR: 1.56 (1.02-2.39), P = 0.04]. However, the combination of STr with RVEF was the most powerful predictor of cardiovascular death. Tricuspid annular plane systolic excursion was not an independent predictor of cardiac survival. CONCLUSIONS: Right ventricular systolic function remains a powerful independent predictor of the clinical outcome. Even in the context of a complete echocardiographic assessment, radionuclide RVEF continues to be the most powerful RV systolic parameter for cardiac survival prediction. However, the determination of STr, in addition to RVEF, could improve risk stratification.


Subject(s)
Ventricular Dysfunction, Left/mortality , Ventricular Function, Right/physiology , Echocardiography, Doppler/methods , Female , Humans , Male , Middle Aged , Observer Variation , ROC Curve , Radionuclide Angiography/methods , Risk Assessment , Stroke Volume/physiology , Systole/physiology , Tricuspid Valve/physiology , Vascular Resistance/physiology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology
20.
Nucl Med Commun ; 33(1): 34-42, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22044864

ABSTRACT

INTRODUCTION: [¹8F]-Fluorodeoxyglucose PET has become an essential technique in oncology. Accurate segmentation is important for treatment planning. With the increasing number of available methods, it will be useful to establish a reliable evaluation tool. METHOD: Five methods for [F]-fluorodeoxyglucose PET image segmentation (MIP-based, Fuzzy C-means, Daisne, Nestle and the 42% threshold-based approach) were evaluated on non-Hodgkin's lymphoma lesions by comparing them with manual delineations performed by a panel of experts. The results were analyzed using different similarity measures. Intraoperator and interoperator variabilities were also studied. RESULTS: The maximum of intensity projection-based method provided results closest to the manual delineations set [binary Jaccard index mean (SD) 0.45 (0.15)]. The fuzzy C-means algorithm yielded slightly less satisfactory results. The application of a 42% threshold-based approach yielded results furthest from the manual delineations [binary Jaccard index mean (SD) 0.38 (0.16)]; the Daisne and the Nestle methods yielded intermediate results. Important intraoperator and interoperator variabilities were demonstrated. CONCLUSION: A simple assessment framework based on comparisons with manual delineations was proposed. The use of a set of manual delineations performed by five different experts as the reference seemed to be suitable to take the intraoperator and the interoperator variabilities into account. The online distribution of the data set generated in this study will make it possible to evaluate any new segmentation method.


Subject(s)
Algorithms , Image Processing, Computer-Assisted/methods , Lymphoma, Non-Hodgkin/diagnostic imaging , Pattern Recognition, Automated/methods , Positron-Emission Tomography/methods , Fluorodeoxyglucose F18 , Fuzzy Logic , Humans , Image Processing, Computer-Assisted/standards , Observer Variation , Pattern Recognition, Automated/standards , Positron-Emission Tomography/instrumentation , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity
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