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1.
Eur J Nucl Med Mol Imaging ; 50(11): 3439-3451, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37341747

RESUMO

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.


Assuntos
Boidae , Neoplasias da Próstata , Masculino , Animais , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antígeno Prostático Específico , Estudos Prospectivos , Neoplasias da Próstata/cirurgia , Recidiva Local de Neoplasia
2.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36835030

RESUMO

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Prognóstico , Inibidores de Checkpoint Imunológico , Estado Nutricional , Estudos Retrospectivos , Inflamação
3.
Blood ; 131(13): 1456-1463, 2018 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-29437590

RESUMO

We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. iPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale (DS). The prognostic value of TMTV was evaluated and compared with baseline characteristics, staging classifications, and iPET2. A total of 258 patients were eligible: 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 progression-free survival (PFS) and 12 overall survival (OS) events. TMTV was a prognosticator of PFS (P < .0001) and OS (P = .0001), with 86% and 84% specificity, respectively. Five-year PFS and OS were 71% and 83% in the high-TMTV (>147 cm3) group (n = 46), respectively, vs 92% and 98% in the low-TMTV group (≤147 cm3). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared with the current staging systems proposed by the European Organization for Research and Treatment of Cancer/Groupe d'Etude des Lymphomes de l'Adulte, German Hodgkin Study Group, or National Comprehensive Cancer Network. TMTV and iPET2 were independently prognostic and, combined, identified 4 risk groups: low (TMTV≤147+DS1-3; 5-year PFS, 95%), low-intermediate (TMTV>147+DS1-3; 5-year PFS, 81.6%), high-intermediate (TMTV≤147+DS4-5; 5-year PFS, 50%), and high (TMTV>147+DS4-5; 5-year PFS, 25%). TMTV improves baseline risk stratification of patients with early-stage HL compared with current staging systems and the predictive value of early PET response as well.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/metabolismo , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Vimblastina/administração & dosagem
4.
Eur J Nucl Med Mol Imaging ; 43(7): 1323-36, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26816194

RESUMO

PURPOSE: Quantitative estimates of dopamine transporter availability, determined with [(123)I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [(123)I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. METHODS: Of 73 healthy subjects from the European Normal Control Database of [(123)I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEM reconstruction including attenuation correction, and camera-specific "to kBq/ml" calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [(123)I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. RESULTS: The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm. CONCLUSION: QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [(123)I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding.


Assuntos
Bases de Dados Factuais , Voluntários Saudáveis , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tropanos/metabolismo , Fatores Etários , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Europa (Continente) , Humanos , Sensibilidade e Especificidade
5.
Eur J Nucl Med Mol Imaging ; 41(10): 1938-46, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24806112

RESUMO

PURPOSE: Apart from binding to the dopamine transporter (DAT), [(123)I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. METHODS: SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. RESULTS: Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. CONCLUSION: The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [(123)I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [(123)I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors.


Assuntos
Neostriado/diagnóstico por imagem , Ponte/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Tálamo/diagnóstico por imagem , Tropanos/farmacocinética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Ligação Proteica , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Fatores Sexuais , Tomografia Computadorizada de Emissão de Fóton Único
6.
Neuroimage ; 64: 61-7, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22982354

RESUMO

INTRODUCTION: Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine transporter (DAT) availability is also decreased. In this study, we tested whether BMI and striatal DAT availability are associated. METHODS: The study included 123 healthy individuals from a large European multi-center database. They had a BMI range of 18.2-41.1 kg/m(2) and were scanned using [(123)I]FP-CIT SPECT imaging. Scans were analyzed with both region-of-interest and voxel-based analysis to determine the binding potential for DAT availability in the caudate nucleus and putamen. A direct relation between BMI and DAT availability was assessed and groups with high and low BMI were compared for DAT availability. RESULTS: No association between BMI and striatal DAT availability was found. CONCLUSION: The lack of an association between BMI and striatal DAT availability suggests that the regulation of striatal synaptic dopamine levels by DAT plays no or a limited role in the pathophysiology of overweight and obesity.


Assuntos
Envelhecimento/metabolismo , Índice de Massa Corporal , Corpo Estriado/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Tropanos/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Corpo Estriado/diagnóstico por imagem , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
7.
Eur J Nucl Med Mol Imaging ; 40(2): 213-27, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23160999

RESUMO

PURPOSE: Dopamine transporter (DAT) imaging with [(123)I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [(123)I]FP-CIT SPECT scans in healthy controls. METHODS: SPECT data from 139 healthy controls (74 men, 65 women; age range 20-83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR). RESULTS: A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade. CONCLUSION: This study provides a large database of [(123)I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference database for nuclear medicine centres and for clinical trials using [(123)I]FP-CIT SPECT as the imaging marker.


Assuntos
Encéfalo/patologia , Valores de Referência , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos/farmacologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Calibragem , Estudos de Casos e Controles , Bases de Dados Factuais , Demência/diagnóstico , Demência/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Humanos , Radioisótopos do Iodo/farmacologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Medicina Nuclear/métodos , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/diagnóstico por imagem , Fatores Sexuais
8.
Cancers (Basel) ; 15(15)2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-37568692

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is associated with a higher lung cancer (LC) risk and may impact cancer's clinical characteristics, treatment strategies, and outcomes. This impact's extent is unclear, particularly in Caucasians. METHODS: In this retrospective observational study, we reviewed the files of all LC patients diagnosed in a 38-month period. Expert radiologists reviewed the computed tomography scans performed at diagnosis. Patients with LC and ILD (n = 29, 7%) were compared to those without ILD (n = 363, 93%) for population and cancer characteristics, treatments, and clinical outcomes. RESULTS: Patients with LC and ILD were older (73 ± 8 vs. 65 ± 11 years; p < 0.001). There was no significant difference in LC histology, localization, stage, or treatment modalities. The respiratory complication rate after cancer treatment was significantly higher in the ILD group (39% vs. 6%; p < 0.01). Overall survival rates were similar at 12 (52% vs. 59%; p = 0.48) and 24 months (41% vs. 45%; p = 0.64) but poorer in the ILD group at 36 months, although not statistically significant (9% vs. 39%; p = 0.06). The ILD group had a higher probability of death (hazard ratio (HR) = 1.49 [0.96;2.27]), but this was not statistically significant (p = 0.06). In a Cox regression model, patients with ILD treated surgically had a significantly higher mortality risk (HR = 2.37 [1.1;5.09]; p = 0.03). CONCLUSIONS: Patients with combined LC and ILD have worse clinical outcomes even when similar treatment modalities are offered.

9.
J Clin Oncol ; 41(2): 327-335, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35867960

RESUMO

PURPOSE: The prognosis of patients with early-stage unfavorable Hodgkin lymphoma remains unsatisfactory. We assessed the efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) in previously untreated, early-stage unfavorable Hodgkin lymphoma (ClinicalTrials.gov identifier: NCT02292979). METHODS: BREACH is a multicenter, randomized, open-label, phase II trial. Eligible patients were age 18-60 years with ≥ 1 unfavorable EORTC/LYSA criterion. Patients were randomly assigned (2:1) to four cycles of BV-AVD or standard doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD), followed by 30 Gy involved node radiotherapy. The primary end point was the positron emission tomography (PET) response rate after two cycles by expert independent review using the Deauville score. The study was designed to test if the PET-negative rate after two cycles of BV-AVD was superior to 75%. We hypothesized a 10% increase in the PET-negative rate after two cycles of BV-AVD. RESULTS: Between March 2015 and October 2016, 170 patients were enrolled. After two cycles, the primary end point of the study was met: 93 (82.3%; 90% CI, 75.3 to 88.0) of 113 patients in the BV-AVD arm were PET-negative (Deauville score 1-3) compared with 43 (75.4%; 90% CI, 64.3% to 84.5%) of 57 in the ABVD arm. The 2-year progression-free survival (PFS) was 97.3% (95% CI, 91.9 to 99.1) and 92.6% (95% CI, 81.4% to 97.2%) in the BV-AVD and ABVD arms, respectively. High total metabolic tumor volume was associated with a significantly shorter PFS (hazard ratio, 17.9; 95% CI, 2.2 to 145.5; P < .001). For patients with high total metabolic tumor volume, the 2-year PFS rate was 90.9% (95% CI, 74.4 to 97.0) and 70.7% (95% CI, 39.4% to 87.9%) in the BV-AVD and ABVD arms, respectively. CONCLUSION: BV-AVD demonstrated an improvement in the PET-negative rate compared with ABVD after two cycles.


Assuntos
Doença de Hodgkin , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Brentuximab Vedotin , Bleomicina , Vimblastina , Doxorrubicina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dacarbazina , Estadiamento de Neoplasias , Resultado do Tratamento
10.
J Urol ; 187(1): 265-71, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22100009

RESUMO

PURPOSE: Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS: We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS: A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS: A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.


Assuntos
Técnicas de Apoio para a Decisão , Febre/complicações , Infecções Urinárias/complicações , Refluxo Vesicoureteral/etiologia , Feminino , Previsões , Humanos , Lactente , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Refluxo Vesicoureteral/epidemiologia
11.
Front Oncol ; 12: 985446, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419902

RESUMO

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA ALK-rearranged lung adenocarcinoma who developed a BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of BRAF A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of BRAF mutation in NSCLC, and BRAF A598-T599insV mutation in other cancers.

12.
Diagnostics (Basel) ; 12(11)2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36428830

RESUMO

D-dimer is a multifaceted biomarker of concomitant activation of coagulation and fibrinolysis, which is routinely used for ruling out pulmonary embolism (PE) and/or deep vein thrombosis (DVT) combined with a clinical pretest probability assessment. The intended use of the tests depends largely on the assay used, and local guidance should be applied. D-dimer testing may suffer from diagnostic errors occurring throughout the pre-analytical, analytical, and post-analytical phases of the testing process. This review aims to provide an overview of D-dimer testing and its value in diagnosing PE and discusses the variables that may impact the quality of its laboratory assessment.

13.
Leuk Lymphoma ; 63(13): 3063-3071, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35975738

RESUMO

This phase I/II study assessed the combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) as a second-line therapy in refractory/relapsed (R/R) classical Hodgkin lymphoma (cHL) patients. Phase I study was designed to determine the maximum tolerated dose (MTD) of BV (10 patients) and phase II evaluated the rate of complete metabolic response (CMR) after 2 cycles of BV-ICE (42 patients). There were no dose-limiting toxicities (DLT) during phase I recommending BV 1.8 mg/kg for phase II. Twenty-six patients (61.9%) achieved CMR after 2 cycles of BV-ICE and 37 patients (88%) were transplanted. With a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) rate were 64.3% and 100%, respectively. Hematological toxicities (81%) and infections (21%) were the most frequent adverse event encountered BV-ICE regimen is feasible with manageable toxicities and could be an alternative to other salvage treatments. Trial Registration: ClinicalTrials.gov identifier: NCT02686346.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin , Linfoma , Recidiva Local de Neoplasia , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin/uso terapêutico , Carboplatina/uso terapêutico , Etoposídeo/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Ifosfamida/uso terapêutico , Imunoconjugados/uso terapêutico , Linfoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do Tratamento
14.
J Pediatr ; 159(4): 644-51.e4, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21511275

RESUMO

OBJECTIVE: To assess the predictive value of procalcitonin, a serum inflammatory marker, in the identification of children with first urinary tract infection (UTI) who might have high-grade (≥3) vesicoureteral reflux (VUR). STUDY DESIGN: We conducted a meta-analysis of individual data, including all series of children aged 1 month to 4 years with a first UTI, a procalcitonin (PCT) level measurement, cystograms, and an early dimercaptosuccinic acid scan. RESULTS: Of the 152 relevant identified articles, 12 studies representing 526 patients (10% with VUR ≥3) were included. PCT level was associated with VUR ≥3 as a continuous (P = .001), and as a binary variable, with a 0.5 ng/mL preferred threshold (adjusted OR, 2.5; 95% CI, 1.1 to 5.4). The sensitivity of PCT ≥0.5 ng/mL was 83% (95% CI, 71 to 91) with 43% specificity rate (95% CI, 38 to 47). In the subgroup of children with a positive results on dimercaptosuccinic acid scan, PCT ≥0.5 ng/mL was also associated with high-grade VUR (adjusted OR, 4.8; 95% CI, 1.3 to 17.6). CONCLUSIONS: We confirmed that PCT is a sensitive and validated predictor strongly associated with VUR ≥3, regardless of the presence of early renal parenchymal involvement in children with a first UTI.


Assuntos
Calcitonina/sangue , Precursores de Proteínas/sangue , Refluxo Vesicoureteral/diagnóstico , Peptídeo Relacionado com Gene de Calcitonina , Pré-Escolar , Dilatação Patológica , Humanos , Lactente , Recém-Nascido , Rim/diagnóstico por imagem , Valor Preditivo dos Testes , Radiografia , Cintilografia , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Ácido Dimercaptossuccínico Tecnécio Tc 99m , Ultrassonografia , Bexiga Urinária/diagnóstico por imagem , Sistema Urinário/patologia , Infecções Urinárias/diagnóstico
15.
J Mater Sci Mater Med ; 22(3): 671-82, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21287241

RESUMO

Surface properties of nanoparticles to be used for radioimmunotherapy need to be optimized to allow antibody conjugation while ensuring biocompatibility. We aimed to investigate cell adhesion and proliferation onto different coatings to be used for nanoparticles. C, CH(x) or SiO(x) coatings deposited onto glass coverslips by magnetron deposition as well as nitrogen functionalized materials synthetized using different reactive sputtering conditions and PPAA (plasma polymerized allylamine) coating, were compared. Amine functionalization did increase hydrophilicity in all the materials tested. Biocompatibility was assessed by measuring cell viability, morphology, attachment, spreading, and pro-inflammatory cytokine secretion. The results show that C and CN(x) were the most biocompatible substrates while SiO(x) and SiO(x)N(y) were the most toxic materials. PPAA coatings displayed unexpectedly an intermediate biocompatibility. A correlation could be observed between wettability and cell proliferation except for C coated surface, indicating that more complex processes than hydrophilicity alone are taking place that affect cell functions.


Assuntos
Alilamina/química , Aminas/química , Anticorpos/química , Materiais Biocompatíveis/química , Adesão Celular , Sobrevivência Celular , Materiais Revestidos Biocompatíveis/química , Citocinas/metabolismo , Células Endoteliais/citologia , Vidro , Humanos , Inflamação , Nanopartículas/química , Nanotecnologia/métodos , Radioimunoterapia/métodos , Propriedades de Superfície
16.
Clin Nucl Med ; 46(1): 38-39, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33156042

RESUMO

Myelolipoma is a rare mesenchymal tumor consisting of adipose tissue and hematopoietic cells. Found usually in the adrenal region, however, few cases have been reported in extra-adrenal regions, most frequently in the presacral region. It is important to recognize such tumor, as it can attain massive size and causes pressure symptoms, and needs to be differentiated from malignant tumors, including liposarcomas. Although CT and MRI can suggest a diagnosis of myelolipoma, these are not conclusive. The hematopoietic cells are enhanced by a Tc-albumin nanocolloid scintigraphy and help to distinguish myolipoma from other entities.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Mielolipoma/diagnóstico por imagem , Agregado de Albumina Marcado com Tecnécio Tc 99m , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Cintilografia
17.
Case Rep Oncol ; 14(2): 700-705, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177519

RESUMO

Eccrine porocarcinoma is a rare malignant cutaneous tumor with high rates of extracutaneous spread, and its diagnosis and management can be quite challenging. This is a case of an 82-year-old woman presenting with an asymptomatic and chronic pubic skin lesion for whom the work-up required many investigations and procedures to confirm the diagnosis of metastatic eccrine porocarcinoma. Indeed, the patient underwent a wide local excision of the skin lesion, imaging with an FDG-PET scan, a colonoscopy, and two inguinal node dissections. As illustrated in this case, surgery should always be considered to achieve disease remission. Other treatments such as chemotherapy and radiotherapy have also been reported in the literature without clear standard guidelines.

18.
Eur J Nucl Med Mol Imaging ; 37(2): 443-50, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19838702

RESUMO

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of clinical dopamine transporter (DAT) single photon emission computed tomography (SPECT) studies using (123)I-labelled radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT imaging, which will increase the diagnostic impact of this technique in neurological practice. The present document is an update of the 2002 guidelines [1] and has been guided by the views of various national societies: the Task Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [2], a consensus statement of the imaging centres included in the "Kompetenznetz-Parkinson" sponsored by the German Federal Ministry of Education, and the Task Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine [3]. The guidelines reflect the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Dopamina/farmacocinética , Tomografia por Emissão de Pósitrons/normas , Guias de Prática Clínica como Assunto , Receptores de Dopamina D2/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/normas , União Europeia , Feminino , Humanos , Masculino , Compostos Radiofarmacêuticos/farmacocinética , Transmissão Sináptica/fisiologia
19.
Eur J Nucl Med Mol Imaging ; 37(2): 434-42, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19838704

RESUMO

The guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aims of the guidelines are to assist nuclear medicine practitioners in making recommendations, performing, interpreting and reporting the results of clinical dopamine D2 receptor SPECT or PET studies, and to achieve a high quality standard of dopamine D2 receptor imaging, which will increase the impact of this technique in neurological practice.The present document is an update of the first guidelines for SPECT using D2 receptor ligands labelled with (123)I [1] and was guided by the views of the Society of Nuclear Medicine Brain Imaging Council [2], and the individual experience of experts in European countries. The guidelines intend to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Dopamina/farmacocinética , Tomografia por Emissão de Pósitrons/normas , Guias de Prática Clínica como Assunto , Receptores de Dopamina D2/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/normas , União Europeia , Feminino , Humanos , Masculino , Compostos Radiofarmacêuticos/farmacocinética , Transmissão Sináptica/fisiologia
20.
Acta Oncol ; 49(2): 192-200, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20059314

RESUMO

OBJECTIVES: Most guidelines consider FDG PET-CT to detect occult extra-pulmonary disease prior to lung metastasectomy. A cost-effectiveness analysis, using a Markov model over a 10 year period, was performed to compare two different surveillance programs, either PET-CT or whole-body CT, in patients with suspected pulmonary metastasised melanoma. METHODS: Data from published studies provided probabilities for the model. Complication and care costs were obtained from standardised administrative databases from 19 hospitals identified by DRG codes (reported in 2009 Euros). For the cost calculation of PET-CT we performed a microcosting analysis. All costs and benefits were yearly discounted at respectively 3% and 1.5%. Outcomes included life-months gained (LMG) and the number of futile surgeries avoided. Cost-effectiveness ratios were in Euros per LMG. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters. RESULTS: The PET-CT strategy provided 86.29 LMG (95% CI: 81.50-90.88 LMG) at a discounted cost of euro3,974 (95% CI: euro1,339-12,303), while the conventional strategy provided 86.08 LMG (95% CI: 81.37-90.68 LMG) at a discounted cost of euro5,022 (95% CI: euro1,378-16,018). This PET-CT strategy resulted in a net saving of euro1,048 with a gain of 0.2 LMG. Based on PET-CT findings, 20% of futile surgeries could be avoided. CONCLUSION: Integrating PET-CT in the management of patients with high risk MM appears to be less costly and more accurate by avoiding futile thoracotomies in one of five patients as well as by providing a small survival benefit at 10 years.


Assuntos
Neoplasias Pulmonares/economia , Melanoma/economia , Tomografia por Emissão de Pósitrons/economia , Neoplasias Cutâneas/economia , Tomografia Computadorizada por Raios X/economia , Análise Custo-Benefício , Fluordesoxiglucose F18/economia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Melanoma/diagnóstico , Melanoma/secundário , Compostos Radiofarmacêuticos/economia , Neoplasias Cutâneas/diagnóstico
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