Interim FDG18-PET SUVmax Variation Adds Prognostic Value to Deauville 5-Point Scale in the Identification of Patients with Ultra-High-Risk Diffuse Large B Cell Lymphoma.

INTRODUCTION: Interim response evaluation by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (iPET) in diffuse large B cell lymphoma (DLBCL) could be important to rule out disease progression and has been suggested to be predictive of survival. However, treatment guidance by iPET is not yet recommended for DLBCL in clinical practice. We aimed to compare the predictive value of iPET when utilizing the visual Deauville 5-point scale (DS) and the semiquantitative variation of maximum standardized uptake value (ΔSUVmax). MATERIALS AND METHODS: We included 85 patients diagnosed with DLBCL and uniformly treated with standard protocols. iPET with DS of 1-3 and/or ΔSUVmax ≥66% was defined as negative. Univariable and multivariable Cox regression analyses were performed to determine the independent factors affecting progression free survival (PFS) or overall survival (OS) and to estimate PFS and OS. RESULTS: iPET positivity, measured by DS or ΔSUVmax, showed predictive value of disease refractoriness, improved by combining DS and ΔSUVmax. After a median follow-up of 50.1 months, iPET was an independent predictor for both PFS and OS when interpreted by DS, but only for PFS by ΔSUVmax. Combined visual and semiquantitative analysis (D4-5 & ΔSUVmax<66%) was an independent predictor of PFS and OS, and allowed to identify an ultra-high-risk subgroup of patients with very dismal outcome, increasing the discriminating capacity for iPET. CONCLUSION: Our study suggests that combined DS and ΔSUVmax in iPET assessment predicts refractory disease and distinguishes ultra-high-risk DLBCL patients with a very dismal prognosis, who may benefit from PET-guided therapy adjustment.

Risk Stratification and Cardiac Sympathetic Activity Assessment Using Myocardial [123I] MIBG Imaging in Renal Denervation. / Estratificação de Risco e Avaliação da Atividade Simpática Cardíaca Utilizando Imagem Miocárdica com [123I] MIBG na Denervação Renal.

Hyperactivation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension. The aim of this study was to assess cardiac sympathetic activity and investigate the role of myocardial123I-labelled meta-iodo benzyl guanidine ([123I] MIBG) scintigraphy in cardiovascular risk stratification of patients with resistant hypertension treated with renal denervation (RDN). Eighteen patients were included in this prospective study (mean age 56 ± 10 years old, 27.8% females). Transthoracic echocardiogram, general blood analysis and myocardial ([123I] MIBG scintigraphy were performed before and six-months after RDN. A patient was considered a responder (R) if a drop ≥ 5mmHg on mean systolic ambulatory blood pressure (BP) monitoring was observed at the six-month follow-up. 66.7% of patients were R (drop in systolic BP of 20.6 ± 14.5mmHg, vs minus 8 ± 11.6mmHg in non-responders (NR), p=0.001). Early heart-mediastinum ratio (HMR) was significantly lower at baseline in the R group (1.6 ± 0.1 vs 1.72 ± 0.1, p<0.02) but similar at six months. Considering both instants in time, the R group had lower early HMR values than the NR group (p<0.05). Both the late HMR and the washout rate were identical and no significant correlation between response to RDN or any MIBG imaging index was found. Renal denervation effectively lowered blood pressure in the majority of patients but [123I] MIBG was not useful in predicting the response. However, there was evidence of sympathetic overdrive and, both early and late HMR were overall reduced, probably putting this population at a higher risk of adverse events.

A hiperativação do sistema nervoso simpático desempenha um papel central na fisiopatologia da hipertensão. O objetivo deste estudo foi avaliar a atividade simpática cardíaca e investigar o papel da cintigrafia miocárdica com metaiodobenzilguanidina com 123I ([123I] MIBG) na estratificação de risco cardiovascular de pacientes com hipertensão resistente tratados com denervação renal (DR). Dezoito pacientes foram incluídos neste estudo prospectivo (média de idade de 56 ± 10 anos, 27,8% mulheres). Ecocardiograma transtorácico, análise geral do sangue e cintilografia miocárdica com [(123I) MIBG] foram realizados antes e seis meses após a DR. Um paciente era considerado respondedor (R) se uma diminuição ≥ 5 mmHg na pressão arterial sistólica (PAS) média ambulatorial fosse observada no seguimento de seis meses. 66,7% dos pacientes foram R (diminuição na PAS de 20,6 ± 14,5 mmHg, vs. menos 8 ± 11,6 mmHg em não-respondedores (NR), p = 0,001). A relação coração-mediastino (RCM) inicial foi significativamente menor na linha basal no grupo R (1,6 ± 0,1 vs. 1,72 ± 0,1, p <0,02), mas semelhante em seis meses. Considerando os dois momentos no tempo, o grupo R teve valores iniciais de RCM mais baixos do que o grupo NR (p <0,05). Tanto o RCM tardio quanto a taxa de washout foram idênticos e nenhuma correlação significativa entre a resposta à DR ou qualquer índice de imagem com MIBG foi encontrada. A denervação renal efetivamente reduziu a pressão arterial na maioria dos pacientes, mas a imagem com [123I] MIBG não foi útil na previsão da resposta. Entretanto, houve evidência de overdrive do sistema nervoso simpático e, tanto a RCM inicial quanto tardia estavam reduzidas em geral, provavelmente colocando essa população em um risco maior de eventos adversos.

[18F]FDG-PET in cardiac sarcoidosis: A single-centre study in a southern European population.

BACKGROUND: Cardiac sarcoidosis (CS) is clinically diagnosed in 5% of patients with sarcoidosis but imaging studies suggest higher prevalence. We evaluated the prevalence, clinical manifestations, and cardiovascular outcomes of CS, diagnosed through 18F-Fluorodeoxyglucose positron emission tomography ([18F]FDG-PET), in a southern European population. METHODS: Retrospective single-centre study of patients screened for sarcoidosis with [18F]FDG-PET. Subjects with histological confirmation were divided in two groups, CS or extracardiac sarcoidosis, according to Heart Rhythm Society's criteria. Primary endpoint was defined as the composite of heart failure hospitalizations, uncontrolled arrythmias, pacemaker implantation, and cardiovascular (CV) mortality. Secondary outcomes included each component and all-cause mortality. RESULTS: From 128 patients with biopsy-proven extracardiac sarcoidosis, 10.2% had probable CS, 54% without symptoms of cardiac involvement. Ten patients had suggestive [18F]FDG uptake patterns, three subjects had an indicative cardiac magnetic resonance (CMR). Patients with probable CS had significantly higher prevalence of coronary and valvular disease, heart failure, and atrial fibrillation compared with those without cardiac involvement. During a mean follow-up of 4.0 SD2.7 years, the primary outcome occurred more frequently in patients with probable CS (53.8% vs. 3.5%; HR 25.45; 95% CI 5.27-122.9; p < 0.01) as well as heart failure hospitalizations (46.2% vs. 0.9%), uncontrolled arrhythmias (23.1% vs. 1.7%) and pacemaker implantation (23.1% vs. 0.9%) (p < 0.01 for all). All-cause mortality was three-fold higher in probable CS, despite the absence of statistical significance (15% vs. 5%, p = 0.15). CONCLUSIONS: Among patients with biopsy-proven sarcoidosis, cardiac involvement detected by [18F]FDG-PET or CMR is associated with a higher risk of CV events, irrespective of symptoms.

Estratificação de Risco e Avaliação da Atividade Simpática Cardíaca Utilizando Imagem Miocárdica com [123I] MIBG na Denervação Renal / Risk Stratification and Cardiac Sympathetic Activity Assessment Using Myocardial [123I] MIBG Imaging in Renal Denervation

Resumo A hiperativação do sistema nervoso simpático desempenha um papel central na fisiopatologia da hipertensão. O objetivo deste estudo foi avaliar a atividade simpática cardíaca e investigar o papel da cintigrafia miocárdica com metaiodobenzilguanidina com 123I ([123I] MIBG) na estratificação de risco cardiovascular de pacientes com hipertensão resistente tratados com denervação renal (DR). Dezoito pacientes foram incluídos neste estudo prospectivo (média de idade de 56 ± 10 anos, 27,8% mulheres). Ecocardiograma transtorácico, análise geral do sangue e cintilografia miocárdica com [(123I) MIBG] foram realizados antes e seis meses após a DR. Um paciente era considerado respondedor (R) se uma diminuição ≥ 5 mmHg na pressão arterial sistólica (PAS) média ambulatorial fosse observada no seguimento de seis meses. 66,7% dos pacientes foram R (diminuição na PAS de 20,6 ± 14,5 mmHg, vs. menos 8 ± 11,6 mmHg em não-respondedores (NR), p = 0,001). A relação coração-mediastino (RCM) inicial foi significativamente menor na linha basal no grupo R (1,6 ± 0,1 vs. 1,72 ± 0,1, p <0,02), mas semelhante em seis meses. Considerando os dois momentos no tempo, o grupo R teve valores iniciais de RCM mais baixos do que o grupo NR (p <0,05). Tanto o RCM tardio quanto a taxa de washout foram idênticos e nenhuma correlação significativa entre a resposta à DR ou qualquer índice de imagem com MIBG foi encontrada. A denervação renal efetivamente reduziu a pressão arterial na maioria dos pacientes, mas a imagem com [123I] MIBG não foi útil na previsão da resposta. Entretanto, houve evidência de overdrive do sistema nervoso simpático e, tanto a RCM inicial quanto tardia estavam reduzidas em geral, provavelmente colocando essa população em um risco maior de eventos adversos.

Abstract Hyperactivation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension. The aim of this study was to assess cardiac sympathetic activity and investigate the role of myocardial123I-labelled meta-iodo benzyl guanidine ([123I] MIBG) scintigraphy in cardiovascular risk stratification of patients with resistant hypertension treated with renal denervation (RDN). Eighteen patients were included in this prospective study (mean age 56 ± 10 years old, 27.8% females). Transthoracic echocardiogram, general blood analysis and myocardial ([123I] MIBG scintigraphy were performed before and six-months after RDN. A patient was considered a responder (R) if a drop ≥ 5mmHg on mean systolic ambulatory blood pressure (BP) monitoring was observed at the six-month follow-up. 66.7% of patients were R (drop in systolic BP of 20.6 ± 14.5mmHg, vs minus 8 ± 11.6mmHg in non-responders (NR), p=0.001). Early heart-mediastinum ratio (HMR) was significantly lower at baseline in the R group (1.6 ± 0.1 vs 1.72 ± 0.1, p<0.02) but similar at six months. Considering both instants in time, the R group had lower early HMR values than the NR group (p<0.05). Both the late HMR and the washout rate were identical and no significant correlation between response to RDN or any MIBG imaging index was found. Renal denervation effectively lowered blood pressure in the majority of patients but [123I] MIBG was not useful in predicting the response. However, there was evidence of sympathetic overdrive and, both early and late HMR were overall reduced, probably putting this population at a higher risk of adverse events.

Metabolic active tumour volume quantified on [18F]FDG PET/CT further stratifies TNM stage IV non-small cell lung cancer patients.

PURPOSE: This study aimed to assess whether the whole body metabolic active tumour volume (MTVWB), quantified on staging [18F]FDG PET/CT, could further stratify stage IV non-small cell lung cancer (NSCLC) patients. METHODS: A group of 160 stage IV NSCLC patients, submitted to staging [18F]FDG PET/CT between July 2010 and May 2020, were retrospectively evaluated. MTVWB was quantified. Univariate and multivariate Cox regressions were carried out to assess correlation with overall survival (OS). C-statistic was used to test predictive power. Kaplan-Meier survival curves with Log-Rank tests were performed to compute statistical differences between strata from dichotomized variables and to calculate the estimated mean survival times (EMST). Survival rates at 1 and 5 years were calculated. RESULTS: MTVWB was a statistically significant predictor of OS on univariate (p < 0.0001) and multivariate analyses (p < 0.0001). The multivariate model with MTVWB (Cindex ± SE = 0.657 ± 0.024) worked significantly better as an OS predictor than the cTNM model (Cindex ± SE = 0.544 ± 0.028) (p = 0.003). An EMST of 29.207 ± 3.627(95% CI 22.099-36.316) months and an EMST of 10.904 ± 1.171(95% CI 8.609-13.199) months (Log-Rank p < 0.0001) were determined for patients with MTVWB < 104.3 and MTVWB ≥ 104.3, respectively. In subsamples of stage IVA (cut-off point = 114.5) and IVB patients (cut-off point = 191.1), statistically significant differences between EMST were also reported, with p-values of 0.0001 and 0.0002, respectively. In both substages and in the entire cohort, patients with MTVWB ≥ cut-off points had lower EMST and survival rates. CONCLUSION: Baseline MTVWB, measured on staging [18F]FDG PET/CT, further stratifies stage IV NSCLC patients. This parameter is an independent predictor of OS and provides valuable prognostic information over the 8th edition of cTNM staging.

The Role of Ga-68-PSMA PET/CT in the Initial Staging of Prostate Cancer - A Single Center 4 Year Experience.

BACKGROUND: Recommended imaging modalities for prostate cancer staging have disappointing sensitivities, whereas [68Ga]-PSMA PET/CT (PET-PSMA) shows promising sensitivities and specificities in the initial management of prostate cancer. Recent studies have revealed that a significant change of management when PET-PSMA was used, with favorable negative predictive values. METHODS: In this retrospective study, we analyzed every PET-PSMA performed in our center for initial staging of intermediate and high-risk prostate cancer. Patients were divided into two groups based on whether imaging modalities other than PET-PSMA were performed. In patients submitted to radical prostatectomy, PET-PSMA findings were compared to histological analysis of the specimen. RESULTS: PET-PSMA results of 57 patients were gathered, with 77.2% (n=44) having performed CT scan or bone scan (BS) prior to PET-PSMA. Prostate cancer management strategy was changed in 61.4% (n=27), when PET-PSMA was performed following CT and BS. BS and CT results were consistent with PET-PSMA in 43.2% and 44.8%, respectively. In 30 cases, a curative strategy was used based on PET-PSMA findings. PET-PSMA revealed a negative predictive value of 95.2% in 23 patients submitted to radical prostatectomy with bilateral pelvic lymphadenectomy. Prostate SUV values on preoperative PET-PSMA correlated with initial PSA, ISUP grade, PC risk staging and presence of extraprostatic lesions. CONCLUSIONS: PET-PSMA is a key element for prostate cancer staging and management, with high diagnostic accuracy. More prospective studies need to be implemented to determine its role as a first-line staging tool.

Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey.

Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case-control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial "misdiagnosis."

Metabolic tumor burden quantified on [18F]FDG PET/CT improves TNM staging of lung cancer patients.

PURPOSE: The purpose of our study was to test a new staging algorithm, combining clinical TNM staging (cTNM) with whole-body metabolic active tumor volume (MATV-WB), with the goal of improving prognostic ability and stratification power. METHODS: Initial staging [18F]FDG PET/CT of 278 non-small cell lung cancer (NSCLC) patients, performed between January/2011 and April/2016, 74(26.6%) women, 204(73.4%) men; aged 34-88 years (mean ± SD:66 ± 10), was retrospectively evaluated, and MATV-WB was quantified. Each patient's follow-up time was recorded: 0.7-83.6 months (mean ± SD:25.1 ± 20.3). RESULTS: MATV-WB was an independent and statistically-significant predictor of overall survival (p < 0.001). The overall survival predictive ability of MATV-WB (C index: mean ± SD = 0.7071 ± 0.0009) was not worse than cTNM (C index: mean ± SD = 0.7031 ± 0.007) (Z = -0.143, p = 0.773). Estimated mean survival times of 56.3 ± 3.0 (95%CI:50.40-62.23) and 21.7 ± 2.2 months (95%CI:17.34-25.98) (Log-Rank = 77.48, p < 0.001), one-year survival rate of 86.8% and of 52.8%, and five-year survival rate of 53.6% and no survivors, were determined, respectively, for patients with MATV-WB < 49.5 and MATV-WB ≥ 49.5. Patients with MATV-WB ≥ 49.5 had a mortality risk 2.9-5.8 times higher than those with MATV-WB < 49.5 (HR = 4.12, p < 0.001). MATV-WB cutoff points were also determined for each cTNM stage: 23.7(I), 49.5(II), 52(III), 48.8(IV) (p = 0.029, p = 0.227, p = 0.025 and p = 0.001, respectively). At stages I, III and IV there was a statistically-significant difference in the estimated mean overall survival time between groups of patients defined by the cutoff points (p = 0.007, p = 0.004 and p < 0.001, respectively). At stage II (p = 0.365), there was a clinically-significant difference of about 12 months between the groups. In all cTNM stages, patients with MATV-WB ≥ cutoff points had lower survival rates. Combined clinical TNM-PET staging (cTNM-P) was then tested: Stage I < 23.7; Stage I ≥ 23.7; Stage II < 49.5; Stage II ≥ 49.5; Stage III < 52; Stage III ≥ 52; Stage IV < 48.8; Stage IV ≥ 48.8. cTNM-P staging presented a superior overall survival predictive ability (C index = 0.730) compared with conventional cTNM staging (C index = 0.699) (Z = -4.49, p < 0.001). CONCLUSION: cTNM-P staging has superior prognostic value compared with conventional cTNM staging, and allows better stratification of NSCLC patients.

Radiation dose comparison between V/P-SPECT and CT-angiography in the diagnosis of pulmonary embolism.

PURPOSE: The aim of this study is to compare two routine protocols at our institution, CTPA and V/P-SPECT, in terms of radiation dose to the most exposed organs (lungs and breast) and to the embryo/fetus in the case of pregnant patients. METHODS: At our institution, the CTPA protocol includes a contrast enhanced CT (scan parameters: 100kVp, 700mA, 0.5s/rot, pitch 0.984) and in some cases a non-contrast enhanced CT acquisition (120kVp, 400mA, 0.5s/rot, pitch 1.375). In the V/P-SPECT protocol, ventilation SPECT was performed after inhalation of 99mTc-Technegas, reaching 30MBq in the lungs; perfusion was performed after intravenous administration of 60-120MBq of 99mTc-MAA. The absorbed doses (mGy) to lungs and breast from CTPA were estimated using the "ImPACT CT Patient Dosimetry Calculator". The embryo/fetus dose was estimated for different gestational stages (0-7, 8-12, 13-25 and 26-40weeks) using the web based calculation tool "COnceptus Dose Estimation" (CODE). Doses to organs and embryo/fetus from V/P-SPECT were estimated based on published dose data normalized to administered activity (mGy/MBq). RESULTS: Embryo/fetus absorbed doses are similar for CTPA and V/P-SPECT and bellow 1mGy. The calculated dose to the lungs (breast) was 1.3-10.6 (27-136) times higher from CTPA when compared with V/P-SPECT. CONCLUSION: For the diagnosis of PE in women, if both imaging modalities are available, it is recommended to proceed with V/P-SPECT rather than CTPA due to the considerably lower radiation dose to the breast.

[Superiority of 18F-FNa PET/CT for Detecting Bone Metastases in Comparison with Other Diagnostic Imaging Modalities]. / Superioridade da PET/CT com FNa-F18 na Deteção de Metástases Ósseas quando Comparada com Outros Métodos de Diagnóstico por Imagem.

INTRODUCTION: The 18F-NaF positron emission tomography/computed tomography is being considered as an excellent imaging modality for bone metastases detection. This ability was compared with other imaging techniques. MATERIAL AND METHODS: We retrospectively evaluated 114 patients who underwent 18F-NaF positron emission tomography/ computed tomography. Of these, 49 patients also had bone scintigraphy, 61 18F-FDG positron emission tomography/computed tomography and 10 18F-FCH positron emission tomography/computed tomography. We identified the technique that detected the largest number of bone metastases. For the detection of skeletal metastases with the 18F-NaF positron emission tomography/computed tomography study, the contribution of the positron emission tomography component was compared with the contribution of the computed tomography component. Cases in which 18F-NaF positron emission tomography/computed tomography and bone scintigraphy required further additional tests for diagnosis clarification were registered. RESULTS: The 18F-NaF positron emission tomography/computed tomography was superior to bone scintigraphy in 49% of the patients (p < 0.001); it was superior to 18F-FDG positron emission tomography/computed tomography in 59% of the patients (p < 0.001) and it was superior to 18F-FCH positron emission tomography/computed tomography in 40% of the patients (p < 0.001). None of the compared imaging techniques were superior to 18F-NaF positron emission tomography/computed tomography. The positron emission tomography component was superior to computed tomography in 35% of the cases (p < 0.001). Further investigation was suggested in only 3.5% of patients who underwent 18F-NaF positron emission tomography/computed tomography (45% for bone scintigraphy) (p < 0.001). DISCUSSION: As with other authors, our experience also confirms that 18F-NaF positron emission tomography/computed tomography is an excellent imaging modality for the detection of bone metastases, detecting lesions in more patients and more lesions per patient. CONCLUSION: The 18F-NaF positron emission tomography/computed tomography showed a superior ability for the detection of bone metastases when compared with bone scintigraphy, 18F-FDG positron emission tomography/computed tomography and 18F-FCH positron emission tomography/computed tomography.

Introdução: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 vem sendo considerada como uma modalidade imagiológica com vantagens na pesquisa de metastização óssea. Comparámos a sua capacidade para deteção de metástases ósseas com a de outras técnicas imagiológicas.Material e Métodos: Avaliámos retrospetivamente 114 doentes que realizaram tomografia por emissão de positrões/tomografia computorizada - FNa-F18. Destes, 49 realizaram também cintigrafia óssea, 61 tomografia por emissão de positrões/tomografia computorizada - FDG-F18 e 10 tomografia por emissão de positrões/tomografia computorizada - FCH-F18. Identificámos a técnica que detetou um maior número de metástases ósseas. Comparámos ainda a tomografia por emissão de positrões com a componente tomografia computorizada da tomografia por emissão de positrões/tomografia computorizada - FNa-F18. Registámos as situações  nas quais a tomografia por emissão de positrões/tomografia computorizada FNa-F18 e a cintigrafia óssea necessitaram de exames adicionais para esclarecimento complementar.Resultados: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 foi superior à cintigrafia óssea em 49% dos doentes (p < 0,001); foi superior à tomografia por emissão de positrões/tomografia computorizada - FDG-F18 em 59% dos doentes (p < 0,001) e foi superior à tomografia por emissão de positrões/tomografia computorizada - FCH-F18 em 40% dos doentes (p < 0,001). Nenhuma das técnicas imagiológicas avaliadas lhe foi superior. Na tomografia por emissão de positrões/tomografia computorizada -FNa-F18 a componente tomografia por emissão de positrões foi superior à tomografia computorizada em 35% dos casos (p < 0,001). Foi sugerida investigação complementar em apenas 3,5% dos doentes que realizaram tomografia por emissão de positrões/ tomografia computorizada - FNa-F18 (45% para a cintigrafia óssea) (p < 0,001).Discussão: Em conformidade com o referido por outros autores, a nossa experiência confirma que a tomografia por emissão de positrões/tomografia computorizada - FNa-F18 tem excelente desempenho na deteção de metástases ósseas, sendo capaz de identificar lesões em mais doentes, e em maior número, quando comparada com outras técnicas imagiológicas.Conclusão: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 revelou superioridade na deteção de metástases ósseas comparativamente à cintigrafia óssea, à tomografia por emissão de positrões/tomografia computorizada - FDG-F18 e à tomografia por emissão de positrões/tomografia computorizada - FCH- F18.

TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease.

Context: Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives: To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNMs), and distant metastases. Design and Patients: Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue. Results: We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations. Conclusions: When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.

Assessment of skeletal tumour burden on 18F-NaF PET/CT using a new quantitative method.

PURPOSE: The purpose of this study was to test a method of quantifying skeletal tumour burden with F-NaF PET/CT. PATIENTS AND METHODS: We retrospectively reviewed the charts of 117 patients who underwent F-NaF PET/CT for the detection of bone metastases, 68 women and 49 men, 16-82 years old (mean±SD: 62.9±10.7 years). Mean standardized uptake values (SUVmean) were measured in five anatomic sites to evaluate normal skeleton activity. The influence of sex and age was investigated. Skeletal tumour burden was calculated in 69 exams positive for bone metastases using volumetric data and SUVmean values. Intraobserver and interobserver reproducibility was tested. In 10 patients with breast cancer, skeletal tumour burden in pretreatment and post-treatment F-NaF PET/CT was compared with tumour marker and clinical evolution. RESULTS: The range of normal skeleton SUVmean for the 410 volume of interests analysed was 2.2-5.9 (mean±SD: 4.4±1.5). A threshold of 10 was chosen to exclude F-NaF normal skeleton uptake. An inverse relationship was found between normal skeleton SUVmean and age (r=-0.237; P=0.032). Our results show excellent intraobserver and interobserver reproducibility, with intraclass correlation values of 0.995 and 0.997, respectively. The percentage change in the skeletal tumour burden in response to therapy shows a moderate direct correlation with the percentage variation of the tumour marker (r=0.668; P=0.035). CONCLUSION: The methodology that we used to quantify skeletal tumour burden is easy to perform, highly reproducible and allows for the evaluation of bone tumour response to therapy in a subgroup of breast cancer patients. The possibility of skeletal tumour burden quantification is another advantage of F-NaF PET/CT over the visual and subjective interpretation of bone scintigraphy.

[PET/CT with 18F-Fluorocholine in Patients with Prostatic Cancer in Biochemical Recurrence]. / PET/CT com Fluorocolina-F18 em Doentes com Carcinoma da Próstata em Recidiva Bioquímica.

INTRODUCTION: In prostate cancer, after therapy with curative intent, biochemical recurrence frequently occurs. The purpose of this study was to evaluate the impact of PET/CT with 18F-fluorocholine in restaging these patients and in their orientation, and to analyze the effect of the risk stratification, the values of PSA and the hormone suppression therapy, in the technique sensitivity. MATERIAL AND METHODS: Retrospective analysis of 107 patients with prostate carcinoma in biochemical recurrence who underwent PET/CT with 18F-fluorocholine in our hospital, between December 2009 and May 2014. RESULTS: The overall sensitivity was 63.2% and 80.0% when PSA > 2 ng/mL. It was possible to identify distant disease in 28% of the patients. The sensitivity increased from 40.0%, in patients with low and intermediate risk, to 55.2% in high-risk patients. Without hormonal suppression therapy, the sensitivity was 61.8%, while in the group under this therapy, was 67.7%. DISCUSSION: PET/CT with 18F-fluorocholine provided important information even in patients with low levels of PSA, however, with significantly increased sensitivity in patients with PSA > 2 ng/mL. Sensitivity was higher in high-risk patients compared with low and intermediate risk patients, however, without a statistically significant difference. The hormone suppression therapy does not appear to influence uptake of 18F-fluorocholine in patients resistant to castration. CONCLUSIONS: In this study, PET/CT with 18F-Fluorocholine showed good results in restaging patients with prostate cancer biochemical recurrence, distinguishing between loco regional and systemic disease, information with important consequences in defining the therapeutic strategy.

Introdução: No carcinoma da próstata, é frequente, após terapêutica com intuito curativo, ocorrer recidiva bioquímica. O objectivo deste trabalho foi avaliar o impacto da PET/CT com fluorocolina-F18 no restadiamento e orientação destes doentes e analisar a influência, da estratificação de risco, dos valores do PSA e da terapêutica de supressão hormonal, na sensibilidade da técnica. Material e Métodos: Análise retrospectiva de 107 doentes com carcinoma da próstata em recidiva bioquímica que realizaram PET/CT com fluorocolina-F18 no nosso hospital, entre dezembro de 2009 e maio de 2014. Resultados: A sensibilidade global foi de 63,2% sendo 80,0% quando PSA > 2 ng/mL. Foi possível identificar doença à distância em 28% dos doentes. A sensibilidade aumentou de 40,0% em doentes de risco baixo e intermédio para 55,2% em doentes de alto risco. Sem terapêutica de supressão hormonal, a sensibilidade foi de 61,8% enquanto no grupo sob essa terapêutica, foi de 67,7%. Discussão: A PET/CT com fluorocolina-F18 forneceu informações relevantes, mesmo em doentes com baixos valores do PSA, contudo, com incremento significativo da sensibilidade nos doentes com PSA >2 ng/mL. A sensibilidade foi superior nos doentes de alto risco comparativamente com os de risco baixo e intermédio, contudo, sem uma diferença estatisticamente significativa. A terapêutica de supressão hormonal parece não influenciar a captação de Fluorocolina-F18 nos doentes resistentes à castração. Conclusões: Neste estudo, a PET/CT com fluorocolina-F18 apresentou bons resultados no restadiamento de doentes com carcinoma da próstata em recidiva bioquímica, distinguindo entre doença loco-regional e sistémica, informação com importantes consequências na definição da estratégia terapêutica.

Thyroid carcinoma in children and young adults: retrospective review of 19 cases.

INTRODUCTION: Thyroid carcinoma is rare in children and young adults. Most of management guidelines are based in data from adult population. Several controversies remain regarding the aggressiveness of clinical presentation and therapeutic approach. OBJECTIVE: To evaluate all differentiated thyroid carcinoma patients with less than 20 years-old at presentation reflecting the experience of our unit in relation to diagnosis, treatment and follow-up of this clinical entity. MATERIAL AND METHODS: This is a retrospective review of clinical records of all children and young adults followed at Oncology Consultation of Department of Endocrinology of Centro Hospitalar e Universitário de Coimbra between 1996 and 2012. RESULTS: Nineteen patients with mean age of 16 years old were followed, 13 girls and 6 boys. None of the patients had previous neck irradiation. A palpable cervical mass was the presenting complaint in 84.6%. FNA was performed in 15 patients and was diagnostic or suspicious of malignancy in 71.4%. Total thyroidectomy was performed in 18 cases (94.7%). Papillary carcinoma was identified in all. Vascular invasion and multicentry occurred in 21.1%. Mean tumor size was 2.5cm. Cervical lymph node involvement was diagnosed in 31.6% and distant metastases in 5.2%. The majority of patients (18 in 19) were classified as stage I disease. All patients received thyroxine suppressive therapy and postoperative radioiodine ablation was given to 84.2% (mean dose 85.7mCi). During mean follow-up of almost 6 years, 16 patients remain disease free. CONCLUSION: In our series, cervical lymph node and distant metastases rates were similar to that found in adult population. Overall prognosis was very good.

Introdução: O carcinoma da tiróide é raro em crianças e em adultos jovens. A maior parte das orientações clínicas baseia-se em dados obtidos na população adulta. Persistem diversas controvérsias no que se refere à agressividade da apresentação clínica e da abordagem terapêutica.Objectivo: Avaliar todos os doentes com carcinoma da tiróide com menos de 20 anos no momento da apresentação, reflectindo a experiência da nossa unidade relativamente ao diagnóstico, tratamento e seguimento desta entidade.Material e Métodos: Trata-se de um estudo de revisão retrospectiva dos registos clínicos de todas as crianças e adultos jovens seguidos na Consulta de Oncologia do Serviço de Endocrinologia do Centro Hospitalar e Universitário de Coimbra entre 1996 e 2012 .Resultados: Foram estudados 19 doentes, com uma média etária de 16 anos, sendo 13 do sexo feminino. Nenhum dos doentes fora previamente submetido a irradiação da região do pescoço. A queixa de apresentação era a presença de uma massa cervical palpável em 84,6% dos casos. Foi realizada citologia aspirativa em 15 doentes, que foi diagnóstica ou suspeita de neoplasia em 71,4% dos casos. A tiroidectomia total foi levada a cabo em 18 casos (94,7%). Em todos estes foi identificada a presença de um carcinoma papilar. A invasão vascular e multicêntrica ocorreu em 21,1% dos casos. A dimensão tumoral média foi de 2,5 cm. O envolvimento ganglionar cervical foi diagnosticado em 31,6% dos casos e a presença de metástases à distância foi identificada em 5,2% dos casos. Na maior parte dos doentes (18 em 19), o quadro foi classificado como doença em estadio I. Todos os doentes fizeram terapêutica supressora com tiroxina e 84,2% dos doentes foram submetidos a ablação pós-operatória com iodo radioactivo (dose média de 85,7mCi). Durante um seguimento médio de cerca de 6 anos, 16 doentes permaneceram em remissão.Conclusão: Na nossa série, as taxas de metastização ganglionar cervical e à distância foram semelhantes às encontradas na população adulta. O prognóstico foi globalmente muito satisfatório.

Rest myocardial perfusion imaging: a valuable tool in ED.

BACKGROUND: Acute chest pain is a frequent cause of emergency department (ED) visits. Rest myocardial perfusion imaging (RMPI) during or immediately after an episode of chest pain can provide diagnostic and prognostic information concerning acute coronary syndromes. AIM: Our purpose was to evaluate the RMPI score in risk stratification of chest pain suspected to be of cardiac ischemic origin and negative troponin assessment. METHODS: Ninety-six patients without an ongoing myocardial infarction or a history of coronary artery disease and in whom RMPI was performed in the ED because of chest pain suspected to be related with acute myocardial ischemia were included. Follow-up was performed considering the occurrence of death, myocardial infarction, or revascularization in a 12-month period admission. RESULTS: Fourteen (14.6%) patients had events. According to survival analysis, the variables related with events were a history of angina (hazard ratio [HR], 4.5; P ≤ .01), an ischemic electrocardiogram (HR, 4.0; P ≤ .01), the abnormal RMPI (HR, 11.4; P ≤ .05), and the RMPI score (HR, 1.1; P ≤ .0001). When the variables of interest were forced into a multivariate model, the χ(2) associated with the model that includes clinical and electrocardiogram information was 16.3 (P ≤ .005) and in the model that also includes RMPI score, it was 23.0 (P ≤ .0005). CONCLUSION: In a low- to intermediate-risk group of patients with suspected acute myocardial ischemia, RMPI gives not only diagnostic information but adds prognostic value to the traditional ED risk stratification tools.

Stimulated thyroglobulin at recombinant human TSH-aided ablation predicts disease-free status one year later.

CONTEXT: Thyroglobulin (Tg) levels measured at the time of remnant ablation after thyroid hormone withdrawal (THW) were shown to have prognostic value in predicting disease-free status. OBJECTIVES: Our objectives were to determine whether stimulated Tg levels, measured at the time of remnant ablation performed under recombinant human TSH (rhTSH) stimulation, has value in predicting absence of detectable disease 1 year after radioiodine therapy and to compare the results obtained with this approach with a cohort of patients submitted to ablation after THW. DESIGN: This was a prospective observational study. SETTING AND PATIENTS: The study included 293 consecutive patients treated for a differentiated thyroid carcinoma with no initial evidence of distant metastasis. All patients were submitted to a total or near-total thyroidectomy, followed by ablation either under rhTSH (n = 151) or endogenous TSH stimulation (n = 142). Patients with positive Tg antibodies were excluded. MAIN OUTCOME MEASURES: The predictive value of Tg at ablation was assessed by receiver operating characteristic curve analysis. RESULTS: In the rhTSH group, 96 patients (73.3%) were considered disease-free at 1 year. Stimulated Tg at ablation after rhTSH was found to be an independent prognostic indicator of disease persistence 12 months later. The highest-accuracy cutoff value for absence of detectable disease was defined as 7.2 ng/mL, with a negative predictive value of 90%. In the THW group, Tg at ablation also proved to have independent predictive value. Using the same threshold (7.2 ng/mL), the negative predictive value of Tg was 95% in the THW group. CONCLUSIONS: When rhTSH was used, stimulated Tg at ablation had independent predictive value for disease-free status 1 year later. A low stimulated Tg at rhTSH-aided ablation may be considered a favorable prognosis factor.

Prognosis of normal stress-only gated-SPECT myocardial perfusion imaging: a single center study.

It has been advocated that using the stress followed by rest protocol, if the stress images were normal there is no need of rest images, reducing radiation exposure and costs. Our purpose was to assess the prognosis of a group of patients with normal stress-only gated-SPECT myocardial perfusion imaging. This was retrospective study that includes 790 patients with normal myocardial stress only perfusion gated SPECT images. Images were considered as normal if a homogeneous myocardial distribution of the tracer was associated with a normal ejection fraction. The mean follow-up was of 42.8 ± 13.3 months. The considered events were death of all causes, myocardial infarction and myocardial revascularization. During this period there were 85 events (10.8 %), including 57 deaths of all causes (67.1 %), 9 myocardial infarctions (10.6 %), 19 revascularizations (2.4 %). In the first year of follow-up there were 32 events (4.0 %) and excluding non cardiac deaths there were 8 events (1.0 %). Using Cox survival analysis, diabetes (HR = 2.2; CI = 1.4-3.4; p ≤ 0.0005), the history of coronary artery disease (CAD) (HR = 2.1; CI = 1.3-3.2; p ≤ 0.001), age (HR = 1.0; CI = 1.0-1.0; p ≤ 0.05) and type of stress protocol were related with events (exercise test vs. adenosine) (Exercise test: HR = 0.5; CI = 0.3-0.8; p ≤ 0.01). In a multivariate analysis the independent predictors were diabetes, CAD and the type of stress protocol. Based on these results, normal stress-only images are associated with an excellent prognosis even in patients at higher risk, diabetics and patients with known CAD.

Left ventricular mechanical dyssynchrony in patients with impaired left ventricular function undergoing gated SPECT myocardial perfusion imaging.

INTRODUCTION: Gated SPECT myocardial perfusion imaging (MPI) has been used to quantify mechanical dyssynchrony. Mechanical dyssynchrony appears to be related to response to cardiac resynchronization therapy. OBJECTIVE: To evaluate the presence and predictors of mechanical dyssynchrony in patients with impaired left ventricular function (LVEF) ≤50%. METHODS: The study included 143 consecutive patients referred for gated SPECT MPI with LVEF ≤50%. Gated SPECT MPI was performed according to a stress/rest protocol acquiring images with Tc 99m-tetrofosmin. Emory Cardiac Toolbox software was used for phase analysis and a standard deviation (SD) ≥43° was considered to indicate mechanical dyssynchrony. RESULTS: Mechanical dyssynchrony was present in 53.1% of the patients. Its predictors were diabetes (OR 2.0, p≤0.05), summed stress score (OR 1.1, p≤0.0005), summed rest score (OR 1.1, p≤0.0001), end-diastolic volume (OR 1.0, p≤0.0001), LVEF (OR 0.9, p≤0.0001), LVEF ≤35% (OR 3.1, p≤0.005) and LVEF ≤35% and QRS ≥120 ms (OR 3.5, p≤0.05). In this study QRS width and QRS ≥120 ms were not predictors of mechanical dyssynchrony. CONCLUSIONS: Myocardial perfusion imaging can be used to assess mechanical dyssynchrony. In patients with impaired ventricular function mechanical dyssynchrony was highly prevalent and was related to parameters of left ventricular function and perfusion.

Nuclear medicine training and practice in Portugal.

Nuclear medicine in Portugal has been an autonomous speciality since 1984. In order to obtain the title of Nuclear Medicine Specialist, 5 years of training are necessary. The curriculum is very similar to the one approved under the auspices of the European Union of Medical Specialists, namely concerning the minimum recommended number of diagnostic and therapeutic procedures. There is a final assessment, and during the training the resident is in an approved continuing education programme. Departments are accredited by the Medical College in order to verify their capacity to host nuclear medicine residencies.

Persistent primary hyperparathyroidism: an uncommon location for an ectopic gland--case report and review.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder that mainly affects middle-aged women. Patients are usually asymptomatic. The disease might be ascribable to hyperplasia, carcinoma, and single or multiple adenomas. PHPT may be sporadic or familial, the latter comprising multiple endocrine neoplasia type 1 or 2A, familial benign hypocalciuria hypercalcemia, and hyperparathyroidism-jaw tumor syndrome. The most common causes for persistent PHPT are multiglandular disease, and missed abnormal ectopic or orthotopic parathyroid glands. Imaging localization studies should precede a new surgical intervention. Ectopic parathyroid glands are rarely located at the aortopulmonary window. For diagnosis confirmation, (99m)Tc-sestamibi SPECT/CT seems to be an advantageous test. Another possibility is to perform (99m)Tc-sestamibi followed by thoracic CT or MRI. Parathyroidectomy may be performed by means of median sternotomy, thoracotomy, or video-assisted thoracoscopy. We describe a case of persistent primary hyperparathyroidism due to the presence of an ectopic parathyroid gland found at the aortopulmonary window. As the investigation necessary to clarify the etiology of recurrent nephrolithiasis proceeded, the diagnosis of PHPT was determined. The patient underwent subtotal parathyroidectomy; nevertheless, PHPT persisted. Genetic syndromes that could account for this condition were excluded. Imaging studies available at that time were not able to locate abnormal glands; moreover, the patient refused to undergo surgical exploration. Later, the patient underwent (99m)Tc-sestamibi SPECT/CT, which revealed a parathyroid gland at the aortopulmonary window.