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PURPOSE: Because of atypical response imaging patterns in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs), new biomarkers are needed for a better monitoring of treatment efficacy. The aim of this prospective study was to evaluate the prognostic value of volume-derived positron-emission tomography (PET) parameters on baseline and follow-up 18F-fluoro-deoxy-glucose PET (18F-FDG-PET) scans and compare it with the conventional PET Response Criteria in Solid Tumors (PERCIST). METHODS: Patients with metastatic NSCLC were included in two different single-center prospective trials. 18F-FDG-PET studies were performed before the start of immunotherapy (PETbaseline), after 6-8 weeks (PETinterim1) and after 12-16 weeks (PETinterim2) of treatment, using PERCIST criteria for tumor response assessment. Different metabolic parameters were evaluated: absolute values of maximum standardized uptake value (SUVmax) of the most intense lesion, total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), but also their percentage changes between PET studies (ΔSUVmax, ΔTMTV and ΔTLG). The median follow-up of patients was 31 (7.3-31.8) months. Prognostic values and optimal thresholds of PET parameters were estimated by ROC (Receiver Operating Characteristic) curve analysis of 12-month overall survival (12M-OS) and 6-month progression-free survival (6M-PFS). Tumor progression needed to be confirmed by a multidisciplinary tumor board, considering atypical response patterns on imaging. RESULTS: 110 patients were prospectively included. On PETbaseline, TMTV was predictive of 12M-OS [AUC (Area Under Curve) =0.64; 95% CI: 0.61 to 0.66] whereas SUVmax and TLG were not. On PETinterim1 and PETinterim2, all metabolic parameters were predictive for 12M-OS and 6M-PFS, the residual TMTV on PETinterim1 (TMTV1) being the strongest prognostic biomarker (AUC=0.83 and 0.82; 95% CI: 0.74 to 0.91, for 12M-OS and 6M-PFS, respectively). Using the optimal threshold by ROC curve to classify patients into three TMTV1 subgroups (0 cm3; 0-57 cm3; >57 cm3), TMTV1 prognostic stratification was independent of PERCIST criteria on both PFS and OS, and significantly outperformed them. Subgroup analysis demonstrated that TMTV1 remained a strong prognostic biomarker of 12M-OS for non-responding patients (p=0.0003) according to PERCIST criteria. In the specific group of patients with PERCIST progression on PETinterim1, low residual tumor volume (<57 cm3) was still associated with a very favorable patients' outcome (6M-PFS=73%; 24M-OS=55%). CONCLUSION: The absolute value of residual metabolic tumor volume, assessed 6-8 weeks after the start of ICPI, is an optimal and independent prognostic measure, exceeding and complementing conventional PERCIST criteria. Oncologists should consider it in patients with first tumor progression according to PERCIST criteria, as it helps identify patients who benefit from continued treatment. TRIAL REGISTRATION NUMBER: 2018-A02116-49; NCT03584334.
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Fluordesoxiglucose F18 , Imunoterapia , Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Carga Tumoral , Humanos , Masculino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Feminino , Pessoa de Meia-Idade , Idoso , Imunoterapia/métodos , Estudos Prospectivos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Adulto , Metástase Neoplásica , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Idoso de 80 Anos ou maisRESUMO
PURPOSE: The main objective of this study was to evaluate the ability of a large field Cadmium Zinc Telluride (CZT) camera to estimate thyroid uptake (TU) on single photon emission computed tomography (SPECT) images with and without attenuation correction (Tomo-AC and Tomo-NoAC) compared with Planar acquisition in a series of 23 consecutive patients. The secondary objective was to determine radiation doses for the tracer administration and for the additional Computed Tomography (CT) scan. METHODS: Cross-calibration factors were determined using a thyroid phantom, for Planar, Tomo-AC and Tomo-NoAC images. Then Planar and SPECT/CT acquisitions centered on the thyroid were performed on 5 anthropomorphic phantoms with activity ranging from 0.4 to 10 MBq, and 23 patients after administration of 79.2 ± 3.7 MBq of [99mTc]-pertechnetate. We estimated the absolute thyroid activity (AThA) for the anthropomorphic phantoms and the TU for the patients. Radiation dose was also determined using International Commission on Radiological Protection (ICRP) reports and VirtualDoseTMCT software. RESULTS: Cross-calibration factors were 66.2 ± 4.9, 60.7 ± 0.7 and 26.5 ± 0.3 counts/(MBq s), respectively, for Planar, Tomo-AC and Tomo-NoAC images. Theoretical and estimated AThA for Planar, Tomo-AC and Tomo-NoAC images were statistically highly correlated (r < 0.99; P < 10-4) and the average of the relative percentage difference between theoretical and estimated AThA were (8.6 ± 17.8), (- 1.3 ± 5.2) and (12.8 ± 5.7) %, respectively. Comparisons between TU based on different pairs of images (Planar vs Tomo-AC, Planar vs Tomo-NoAC and Tomo-AC vs Tomo-NoAC) showed statistically significant correlation (r = 0.972, 0.961 and 0.935, respectively; P < 10-3). Effective and thyroid absorbed doses were, respectively (0.34CT + 0.95NM) mSv, and (3.88CT + 1.74NM) mGy. CONCLUSION: AThA estimation using Planar and SPECT/CT acquisitions on a new generation of CZT large-field cameras is feasible. In addition, TU on SPECT/CT was as accurate as conventional planar acquisition, but the CT induced additional thyroid exposure. Trial registration Name of the registry: Thyroid Uptake Quantification on a New Generation of Gamma Camera (QUANTHYC). TRIAL NUMBER: NCT05049551. Registered September 20, 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05049551?cntry=MC&draw=2&rank=4 .
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PURPOSE: We evaluated the prognostic value of immunotherapy-induced organ inflammation observed on 18FDG PET in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). METHODS: Data from patients with IIIB/IV NSCLC included in two different prospective trials were analyzed. 18FDG PET/CT exams were performed at baseline (PETBaseline) and repeated after 7-8 weeks (PETInterim1) and 12-16 weeks (PETInterim2) of treatment, using iPERCIST for tumor response evaluation. The occurrence of abnormal organ 18FDG uptake, deemed to be due to ICPI-related organ inflammation, was collected. RESULTS: Exploratory cohort (Nice, France): PETInterim1 and PETInterim2 revealed the occurrence of at least one ICPI-induced organ inflammation in 72.8% of patients, including midgut/hindgut inflammation (33.7%), gastritis (21.7%), thyroiditis (18.5%), pneumonitis (17.4%), and other organ inflammations (9.8%). iPERCIST tumor response was associated with improved progression-free survival (p < 0.001). iPERCIST tumor response and immuno-induced gastritis assessed on PET were both associated with improved overall survival (OS) (p < 0.001 and p = 0.032). Combining these two independent variables, we built a model predicting patients' 2-year OS with a sensitivity of 80.3% and a specificity of 69.2% (AUC = 72.7). Validation cohort (Genova, Italy): Immuno-induced gastritis (19.6% of patients) was associated with improved OS (p = 0.04). The model built previously predicted 2-year OS with a sensitivity and specificity of 72.0% and 63.6% (AUC = 70.7) and 3-year OS with a sensitivity and specificity of 69.2% and 80.0% (AUC = 78.2). CONCLUSION: Immuno-induced gastritis revealed by early interim 18FDG PET in around 20% of patients with NSCLC treated with ICPI is a novel and reproducible imaging biomarker of improved OS.
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Carcinoma Pulmonar de Células não Pequenas , Gastrite , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Fluordesoxiglucose F18 , Humanos , Fatores Imunológicos , Imunoterapia/efeitos adversos , Inflamação/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
PURPOSE: We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors. METHODS: We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema. RESULTS: We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema. CONCLUSION: In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others. SUMMARY STATEMENT: Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors. KEY RESULTS: In non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.
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COVID-19 , Deterioração Clínica , Cardiopatias , Embolia Pulmonar , Superinfecção , Albuminas , Estado Terminal , Edema/diagnóstico por imagem , Edema/etiologia , Humanos , Pulmão/diagnóstico por imagem , Neovascularização Patológica , SARS-CoV-2 , Volume Sistólico , Função Ventricular EsquerdaRESUMO
PURPOSE: Physiological myocardial accumulation of FDG impairs the diagnosis of inflammatory/infectious or tumoral myocardial detection by FDG PET/CT. We prospectively evaluated the addition, 3 hours before imaging, of an intravenous 100-mL lipid emulsion infusion (Intralipid) to a high-fat, low-carbohydrate diet (HFLCD) for at least 2 meals followed by a fast of at least 6 to 12 hours in patients referred for the diagnosis of myocardial inflammation, endocarditis, cardiac or paracardiac masses, intracardiac device, or prosthetic valve infections. METHODS: Data of 58 patients consecutively included (28 Intralipid patients, 30 controls with HFLCD alone) were compared. FDG uptake in normal myocardium was scored from 0 (complete myocardial suppression) to 3 (high diffuse uptake). Myocardial maximal, peak, and mean SUV and the rate of interpretable images according to the clinical indication were measured. RESULTS: Compared with controls, Intralipid infusion significantly improved the rate of score 0 (89% vs 63%, P = 0.021), of interpretable images according to the clinical indication (100% vs 72%, P = 0.0047) and decreased all myocardial SUV values (eg, SUVmax median, 1.9 [interquartile range, 1.7-2.5] vs 3.1 [interquartile range, 2.3-4.1]; P < 0.001). CONCLUSIONS: A lipid emulsion infusion in addition to HFLCD better suppresses cardiac glucose metabolism than HFLCD alone.
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Emulsões Gordurosas Intravenosas/farmacologia , Fluordesoxiglucose F18 , Glucose/metabolismo , Coração/efeitos dos fármacos , Coração/diagnóstico por imagem , Miocárdio/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Transporte Biológico/efeitos dos fármacos , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: [18F]-2-Fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT) is a sensitive and quantitative technic for detecting inflammatory process. Glucose uptake is correlated with an increased anaerobic glycolysis seen in activated inflammatory cells such as monocytes, lymphocytes, and granulocytes. The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. METHODS: Patients admitted with COVID-19 were prospectively enrolled. FDG PET/CT was performed from day 6 to day 14 of the onset of symptoms. Depending on FDG PET/CT findings, patients' profiles were classified as "inflammatory" or "low inflammatory." FDG PET/CT data were compared with chest CT evolution and short-term clinical outcome. All inflammatory sites were reported to screen potential extra-pulmonary tropism. RESULTS: Thirteen patients were included. Maximum standardized uptake values ranged from 4.7 to 16.3 in lungs. All patients demonstrated increased mediastinal lymph nodes glucose uptake. Three patients (23%) presented mild nasopharyngeal, two patients (15%) bone marrow, and five patients (38%) splenic mild increase in glucose uptake. No patient had significant digestive focal or segmental glucose uptake. There was no significant physiological myocardial glucose uptake in all patients except one. There was no correlation between PET lung inflammatory status and chest CT evolution or short-term clinical outcome. CONCLUSION: Inflammatory process at the presumed peak of the inflammatory phase in COVID-19 patients is obvious in FDG PET/CT scans. Glucose uptake is heterogeneous and typically focused on lungs. TRIAL REGISTRATION: NCT04441489. Registered 22 June 2020 (retrospectively registered).
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COVID-19/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Idoso , Idoso de 80 Anos ou mais , COVID-19/classificação , COVID-19/terapia , Feminino , Coração/diagnóstico por imagem , Humanos , Inflamação/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Purpose To compare the accuracy of a single 20-second deep-inspiration breath hold (DIBH) in fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) to that with conventional free-breathing (FB) whole-body PET/CT for the assessment, characterization, and quantification of lung lesions in terms of the blurring effect of respiratory motion. Materials and Methods Institutional review board approval was obtained, and the requirement to obtain informed consent was waived. A preclinical study was performed in a test population of 19 patients to evaluate the feasibility and consistency of DIBH techniques compared with phase-based respiratory gating (PBRG). One hundred fifteen patients with lung lesions were then prospectively included and assessed with FB PET/CT followed by 20-second DIBH PET/CT. Maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), and number and size of nodules were reported for each acquisition and then compared with findings from histopathologic examination and/or clinical-radiologic follow-up. Statistical analysis was performed with the t test, χ2 test, Pearson correlation coefficient, and receiver operating characteristic analysis. Results In the test population, data obtained with DIBH PET and PBRG PET showed close correlation (r = 0.94, P < .001 for SUVmax and r = 0.98, P < .001 for SUVpeak). In the clinical population, both SUVmax and SUVpeak were significantly increased with DIBH compared with FB (5.60 ± 4.20 vs 3.11 ± 1.80 and 2.25 ± 1.75 vs 1.71 ± 0.96, respectively; P < .001). A significantly greater number of lung lesions was detected with DIBH PET/CT compared with FB PET/CT (P < .001), with the detection of 70 additional nodules and more accurate coregistration of 84. According to the area under the receiver operating characteristic curve for SUVpeak, DIBH demonstrated a higher level of accuracy than did FB (P = .039). Conclusion The DIBH PET/CT technique is feasible in routine clinical practice and is more sensitive for quantitative measurements and lesion localization. This technique reduces the blurring effect of respiratory motion, thus improving the diagnostic accuracy for lung nodules. © RSNA, 2017.
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Suspensão da Respiração , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCAssuntos
Abdome/diagnóstico por imagem , Neoplasias Abdominais/diagnóstico por imagem , Artefatos , Tomografia por Emissão de Pósitrons/métodos , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Técnicas de Imagem de Sincronização Respiratória/métodos , Feminino , Humanos , MasculinoRESUMO
UNLABELLED: PET acquisition requires several minutes which can lead to respiratory motion blurring, to increase partial volume effect and SUV under-estimation. To avoid these artifacts, conventional 10-min phase-based respiratory gating (PBRG) can be performed but is time-consuming and difficult with a non-compliant patient. We evaluated an automatic amplitude-based gating method (AABG) which keeps 35% of the counts at the end of expiration to minimize respiratory motion. We estimated the impact of AABG on upper abdominal lesion detectability, quantification and patient management. METHODS: We consecutively included 31 patients (82 hepatic and 25 perihepatic known lesions). Each patient underwent 3 acquisitions on a Siemens Biograph mCT (4 rings and time-of-flight): a standard free-breathing whole-body (SWB, 5-7 steps/2.5 min per step, 3.3±0.4 MBq/kg of 18F-FDG), a 10-min PBRG with six bins and a 5-min AABG method. All gated acquisitions were performed with an ANZAI respiratory gating system. SUVmax and target to background ratio (TBR, defined as the maximum SUV of the lesion divided by the mean SUV of a region of interest drawn in healthy liver) were compared. RESULTS: All 94 lesions in SWB images were detected in the gated images. 10-min PBRG and 5-min AABG acquisitions respectively revealed 9 and 13 new lesions and relocated 7 and 8 lesions. Four lesions revealed by 5-min AABG were missed by 10-min PBRG in 3 non-compliant patients. Both gated methods failed to relocate 2 lesions seen on SWB acquisition. Compared to SWB, TBR increased significantly with 10-min PBRG and with 5-min AABG (respectively 41±59%, p=4.10-3 and 66±75%, p=6.10-5) whereas SUVmax did not (respectively 14±43%, p=0.29 with 10-min PBRG, and 24±46%, p=0.11 with 5-min AABG). CONCLUSION: The AABG is a fast and a user-friendly respiratory gating method to increase detectability and quantification of upper abdominal lesions compared to the conventional PBRG procedure and the SWB acquisition.
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Abdome/diagnóstico por imagem , Neoplasias Abdominais/diagnóstico por imagem , Artefatos , Tomografia por Emissão de Pósitrons/métodos , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Técnicas de Imagem de Sincronização Respiratória/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
UNLABELLED: Two mitogen-activated protein kinase kinase (MAPK2, also known as MEK) inhibitors were assessed with (18)F-FDG PET in separate phase I clinical studies, clearly illustrating the potential of metabolic imaging for dose, dosing regimen, and compound selection in early-phase trials and utility for predicting nonresponding patients. METHODS: (18)F-FDG PET data were collected during 2 independent, phase I, dose-escalation trials of 2 novel MEK inhibitors (RO5126766 and RO4987655). PET acquisition procedures were standardized between the 2 trials, and PET images were analyzed centrally. Imaging was performed at baseline; at cycle 1, day 15; and at cycle 3, day 1. A 10-mm-diameter region of interest was defined for up to 5 lesions, and peak standardized uptake values were determined for each lesion. The relationship between PET response and pharmacokinetic factors (dose and exposure), inhibition of extracellular-signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells, and anatomic tumor response as measured by Response Evaluation Criteria in Solid Tumors was investigated for both compounds. RESULTS: Seventy-six patients underwent PET, and 205 individual PET scans were analyzed. Strong evidence of biologic activity was seen as early as cycle 1, day 15, for both compounds. (18)F-FDG PET revealed striking differences between the 2 MEK inhibitors at their recommended dose for phase II investigation. The mean amplitude of the decrease in (18)F-FDG from baseline to cycle 1, day 15, was greater for patients receiving RO4987655 than for those receiving RO5126766 (47% vs. 16%, respectively; P = 0.052). Furthermore, a more pronounced relationship was seen between the change in (18)F-FDG uptake and dose or exposure and phosphorylated ERK inhibition in peripheral blood mononuclear cells in patients receiving RO4987655. For both investigational drugs, PET responses tended to be greatest in patients with melanoma tumors. (18)F-FDG was able to identify early nonresponding patients with a 97% negative predictive value. CONCLUSION: These data exemplify the role of (18)F-FDG PET for guiding the selection of novel investigational drugs, choosing dose in early-phase clinical development, and predicting nonresponding patients early in treatment.
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Benzamidas/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Cumarínicos/uso terapêutico , Fluordesoxiglucose F18 , Processamento de Imagem Assistida por Computador , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Oxazinas/uso terapêutico , Tomografia por Emissão de Pósitrons , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Benzamidas/farmacologia , Cumarínicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oxazinas/farmacologia , Fosfoproteínas/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Falha de Tratamento , Adulto JovemRESUMO
PURPOSE: To evaluate the prognostic significance of increased mediastinal (18)F-FDG uptake in PET/CT for the staging of advanced ovarian cancer. METHODS: We retrospectively evaluated patients managed for FIGO stage III/IV ovarian cancer between 1 January 2006 and 1 June 2009. Patients were included if they had undergone (18)F-FDG PET/CT and surgery for initial staging. Exclusion criteria were age younger than 18 years, inability to undergo general anaesthesia, recurrent ovarian cancer, and borderline or nonepithelial malignancy. Whole-body PET/CT was performed after intravenous (18)F-FDG injection. The location of abnormal hot spots and (18)F-FDG maximal standard uptake values (SUV(max)) were recorded. We compared the complete cytoreduction and survival rates in groups defined based on mediastinal (18)F-FDG uptake and SUV(max) values. Kaplan-Meier curves of overall survival and disease-free survival were compared using the log-rank test. Hazard ratios with their 95% confidence intervals were computed. Adjusted hazard ratios were obtained using a multivariate Cox model. RESULTS: We included 53 patients, of whom 17 (32%) had increased mediastinal (18)F-FDG uptake. Complete cytoreduction was achieved in 14 (87.5%) of the 16 patients managed with primary surgery and in 21 (75%) of the 28 patients managed with interval surgery. Complete cytoreduction was achieved significantly more often among patients without increased mediastinal (18)F-FDG uptake (80.6% vs. 35.3%; p = 0.001). Disease-free survival was comparable between the two groups. By univariate analysis, overall mortality was significantly higher among patients with increased mediastinal (18)F-FDG uptake (hazard ratio 5.70, 95% confidence interval 1.74-18.6). The only factor significantly associated with overall survival by multivariate analysis was complete cytoreduction (adjusted hazard ratio 0.24, 95% confidence interval 0.07-0.89). CONCLUSION: Increased mediastinal (18)F-FDG uptake was common in patients with advanced ovarian cancer. However, complete cytoreduction, which was significantly more frequent among patients without mediastinal (18)F-FDG uptake, was the only factor independently associated with survival.
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Fluordesoxiglucose F18/metabolismo , Mediastino , Imagem Multimodal , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Transporte Biológico , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
UNLABELLED: The aims of this cohort study were to evaluate initial tumor hypoxia in metastatic renal cell carcinoma (mRCC) and its changes after sunitinib treatment, using (18)F-fluoromisonidazole PET/CT, and investigate the possible prognostic value of initial tumor hypoxia or its changes under sunitinib therapy. METHODS: Antiangiogenic-naive patients with mRCC were prospectively enrolled in this cohort study. Before initiation of sunitinib, CT defined up to 10 targets that were assessed at 1 and 6 mo according to the response evaluation criteria in solid tumors (RECIST). Pretreatment target uptake of (18)F-fluoromisonidazole was compared with uptake at 1 mo. Targets were considered hypoxic when their maximal standard uptake value was above mean blood value + 2 SDs. Hypoxic volumes were also computed. Relationships between initial hypoxia status, initial degree of hypoxia, its change at 1 mo, and overall or progression-free survival (OS and PFS, respectively) were assessed by survival analysis. RESULTS: Fifty-three patients were included. Median follow-up was 16.8 mo. (18)F-fluoromisonidazole uptake significantly decreased in initially hypoxic target metastases but did not change in others (-22%, P < 10(-4), vs. +1.5%, P = 0.77; P = 10(-3) between groups). Seventy-five percent of patients with hypoxic metastases were free of progressive disease at 4.8 mo (95% confidence interval, 2.99-11.83), compared with 11.3 mo (95% confidence interval, 3.08-36.9) for other patients (P = 0.02), whereas OS was not significantly different. Changes in tumor hypoxia were not related to PFS or OS. CONCLUSION: Sunitinib reduced hypoxia in initially hypoxic RECIST target metastases but did not induce significant hypoxia in nonhypoxic RECIST target metastases. Patients with initially hypoxic targets have shorter PFS than others.
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Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Misonidazol/análogos & derivados , Tomografia por Emissão de Pósitrons , Pirróis/uso terapêutico , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Hipóxia Celular/efeitos dos fármacos , Estudos de Coortes , Progressão da Doença , Humanos , Indóis/farmacologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Pirróis/farmacologia , Sunitinibe , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: We aimed to evaluate the additional information of 18 fluorodeoxyglucose (FDG) arterial uptake with respect to other conventional cardiovascular risk factors and arterial calcifications in patients with stable cancer. METHODS AND RESULTS: We compared the rate of cardiovascular events in 2 groups of patients with (n = 45) and without (n = 56) enhanced arterial 18FDG uptake, matched for the main clinical parameters. The extent and intensity of 18FDG uptake were quantified. A calcification index was also determined. About one third of the selected patients had a history of cardiovascular events and thus could be defined as "vulnerable patients." Old cardiovascular events (>6 months before or after positron emission tomography [PET]) and recent cardiovascular events (<6 months before or after PET) were significantly more frequent in the high-FDG uptake group than in the low-FDG uptake group (48% vs 15%, respectively [P = .0006], and 30% vs 1.8%, respectively [P = .0002]). The extent of 18FDG arterial uptake was the unique factor significantly related to the occurrence of a recent event by either logistic regression or discriminant analysis (P = .004 for all). Conversely, calcium index was the single factor related to old events (P = .004 and P = .002, respectively). CONCLUSIONS: Extensive arterial 18FDG uptake might be an indicator of an evolving atherosclerotic process and should be mentioned in PET/computed tomography reports.