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Arthritis Rheumatol ; 71(7): 1147-1157, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30615273


OBJECTIVE: The usefulness of positron emission tomography-computed tomography (PET-CT) with 18 F-labeled fluorodeoxyglucose (18 F-FDG) for the diagnosis of lymphoma in patients with primary Sjögren's syndrome (SS) is unclear, since the abnormalities it reveals may be due to systemic manifestations of SS. This study was undertaken to compare 18 F-FDG-PET-CT in patients with primary SS with lymphoma and those without lymphoma in order to identify patterns associated with lymphoma. METHODS: A retrospective study was conducted in 2 centers and included patients who met the American College of Rheumatology/European League Against Rheumatism 2016 criteria for primary SS and had undergone PET-CT. Two independent readers who were blinded with regard to lymphoma diagnosis analyzed PET-CT scans. Abnormalities were compared between patients with and those without lymphoma. RESULTS: Of the 45 patients included, 15 had lymphoma. Compared to patients without lymphoma, the mean size (P = 0.048) and maximum standardized uptake value (SUVmax) (P = 0.001) of the parotid glands were higher in patients with lymphoma. FDG uptake in the lymph nodes was observed in 53.3% of the patients with lymphoma and 43.3% of the patients without lymphoma, with no difference in the number of sites, uptake pattern, or mean SUVmax. Focal pulmonary uptake (nodules or condensations) was observed in 5 of the patients with lymphoma (33.3%) but only 1 patient without lymphoma (3.3%) (P = 0.01). Having an SUVmax in the parotid gland of ≥4.7 and/or the presence of focal pulmonary lesions was highly suggestive of lymphoma (sensitivity 80%, specificity 83.3%). CONCLUSION: Some systemic manifestations of primary SS (lymphadenopathy, pulmonary involvement, and salivary gland involvement) can be visualized by PET-CT. Involvement of the lymph nodes and parotid glands is commonly observed with a similar frequency in SS patients with and those without lymphoma. An SUVmax in the parotid glands of ≥4.7 and/or the presence of focal lung lesions are associated with the diagnosis of lymphoma.

Nature ; 558(7711): 540-546, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29899452


CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.

Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Lipoma/tratamento farmacológico , Lipoma/enzimologia , Terapia de Alvo Molecular , Anormalidades Musculoesqueléticas/tratamento farmacológico , Anormalidades Musculoesqueléticas/enzimologia , Nevo/tratamento farmacológico , Nevo/enzimologia , Tiazóis/uso terapêutico , Malformações Vasculares/tratamento farmacológico , Malformações Vasculares/enzimologia , Adulto , Animais , Criança , Modelos Animais de Doenças , Feminino , Células HeLa , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Camundongos , Fenótipo , Escoliose/complicações , Escoliose/tratamento farmacológico , Sirolimo/uso terapêutico , Síndrome , Neoplasias Vasculares/complicações , Neoplasias Vasculares/tratamento farmacológico
Oncotarget ; 9(24): 16822-16831, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29682187


Primary central nervous system lymphoma (PCNSL) is a rare topographic variant of diffuse large B-cell lymphoma (DLBCL). While prognostic scales are useful in clinical trials, no dynamic prognostic marker is available in this disease. We report here the prognostic value of early metabolic response by 18F-FDG PET scanner (PET) in 25 newly diagnosed immunocompetent PCNSL patients. Induction treatment consisted of four cycles of Rituximab, Methotrexate and Temozolamide (RMT). Based on patient's general condition, consolidation by high-dose Etoposide and Aracytine was given to responding patients. Brain MRI and PET were performed at diagnosis, after two and four cycles of RMT, and after treatment completion. Two-year progression-free (PFS) and overall survival (OS) were 62% and 74%, respectively for the whole cohort. Best responses after RMT induction were 18 (72%) complete response (CR)/CR undetermined (CRu), 4 (16%) partial response, 1 (4%) progressive disease and 2 (8%) stable disease. Response evaluation was concordant between MRI and PET at the end of induction therapy. Nineteen patients (76%) had a negative PET2. Predictive positive and negative values of PET2 on end-of-treatment (ETR) CR were 66.67% and 94.74%, respectively. We observed a significant association between PET2 negativity and ETR (p = 0.001) and longer PFS (p = 0.02), while having no impact on OS (p = 0.32). Two years PFS was 72% and 33% for PET2- and PET2+ patients, respectively (p < 0.02). PET2 evaluation may help to early define a subgroup of CR PCNSL patients with a favorable outcome.

J Nucl Med ; 52(11): 1727-32, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21984797


UNLABELLED: We propose a standardized approach to quantitative molecular imaging (MI) in cancer patients with multiple lesions. METHODS: Twenty patients with castration-resistant prostate cancer underwent (18)F-FDG and (18)F-16ß-fluoro-5-dihydrotestosterone ((18)F-FDHT) PET/CT scans. Using a 5-point confidence scale, 2 readers interpreted coregistered scan sets on a workstation. Two hundred three sites per scan (specified in a lexicon) were reviewed. (18)F-FDG-positive lesion bookmarks were propagated onto (18)F-FDHT studies and then manually accepted or rejected. Discordance-positive (18)F-FDHT lesions were similarly bookmarked. Lesional SUV(max) was recorded. Tracer- and tissue-specific background correction factors were calculated via receiver-operating-characteristic analysis of 65 scan sets. RESULTS: Readers agreed on more than 99% of (18)F-FDG- and (18)F-FDHT-negative sites. Positive-site agreement was 83% and 85%, respectively. Consensus-lesion maximum standardized uptake value (SUV(max)) was highly reproducible (concordance correlation coefficient > 0.98). Receiver-operating-characteristic curves yielded 4 correction factors (SUV(max) 1.8-2.6). A novel scatterplot (Larson-Fox-Gonen plot) depicted tumor burden and change in SUV(max) for response assessments. CONCLUSION: Multilesion molecular imaging is optimized with a 5-step approach incorporating a confidence scale, site lexicon, semiautomated PET software, background correction, and Larson-Fox-Gonen graphing.

Processamento de Imagem Assistida por Computador/métodos , Imagem Molecular/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Automação , Biomarcadores Tumorais/metabolismo , Di-Hidrotestosterona/análogos & derivados , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador/normas , Masculino , Imagem Molecular/normas , Imagem Multimodal/normas , Orquiectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Padrões de Referência , Estudos Retrospectivos