Prostate cancer tissue classification by multiphoton imaging, automated image analysis and machine learning.

Prostate carcinoma, a slow-growing and often indolent tumour, is the second most commonly diagnosed cancer among men worldwide. The prognosis is mainly based on the Gleason system through prostate biopsy analysis. However, new treatment and monitoring strategies depend on a more precise diagnosis. Here, we present results by multiphoton imaging for prostate tumour samples from 120 patients that allow to obtain quantitative parameters leading to specific tumour aggressiveness signatures. An automated image analysis was developed to recognise and quantify stromal fibre and neoplastic cell regions in each image. The set of metrics was able to distinguish between non-neoplastic tissue and carcinoma areas by linear discriminant analysis and random forest with accuracy of 89% ± 3%, but between Gleason groups of only 46% ± 6%. The reactive stroma analysis improved the accuracy to 65% ± 5%, clearly demonstrating that stromal parameters should be considered as additional criteria for a more accurate diagnosis.

PET/CT and inflammatory mediators in systemic sclerosis-associated interstitial lung disease.

OBJECTIVE: To investigate the correlation of HRCT findings with pulmonary metabolic activity in the corresponding regions using 18F-FDG PET/CT and inflammatory markers in patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD). METHODS: This was a cross-sectional study involving 23 adult patients with SSc-associated ILD without other connective tissue diseases. The study also involved 18F-FDG PET/CT, HRCT, determination of serum chemokine levels, clinical data, and pulmonary function testing. RESULTS: In this cohort of patients with long-term disease (disease duration, 11.8 ± 8.7 years), a nonspecific interstitial pneumonia pattern was found in 19 (82.6%). Honeycombing areas had higher median standardized uptake values (1.95; p = 0.85). Serum levels of soluble tumor necrosis factor receptor 1, soluble tumor necrosis factor receptor 2, C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand 10 were higher in SSc patients than in controls. Serum levels of CCL2-a marker of fibroblast activity-were correlated with pure ground-glass opacity (GGO) areas on HRCT scans (p = 0.007). 18F-FDG PET/CT showed significant metabolic activity for all HRCT patterns. The correlation between serum CCL2 levels and GGO on HRCT scans suggests a central role of fibroblasts in these areas, adding new information towards the understanding of the mechanisms surrounding cellular and molecular elements and their expression on HRCT scans in patients with SSc-associated ILD. CONCLUSIONS: 18F-FDG PET/CT appears to be unable to differentiate the intensity of metabolic activity across HRCT patterns in chronic SSc patients. The association between CCL2 and GGO might be related to fibroblast activity in these areas; however, upregulated CCL2 expression in the lung tissue of SSc patients should be investigated in order to gain a better understanding of this association.

PET/CT and inflammatory mediators in systemic sclerosis-associated interstitial lung disease / PET/TC e mediadores inflamatórios na doença pulmonar intersticial associada à esclerose sistêmica

ABSTRACT Objective: To investigate the correlation of HRCT findings with pulmonary metabolic activity in the corresponding regions using 18F-FDG PET/CT and inflammatory markers in patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD). Methods: This was a cross-sectional study involving 23 adult patients with SSc-associated ILD without other connective tissue diseases. The study also involved 18F-FDG PET/CT, HRCT, determination of serum chemokine levels, clinical data, and pulmonary function testing. Results: In this cohort of patients with long-term disease (disease duration, 11.8 ± 8.7 years), a nonspecific interstitial pneumonia pattern was found in 19 (82.6%). Honeycombing areas had higher median standardized uptake values (1.95; p = 0.85). Serum levels of soluble tumor necrosis factor receptor 1, soluble tumor necrosis factor receptor 2, C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand 10 were higher in SSc patients than in controls. Serum levels of CCL2-a marker of fibroblast activity-were correlated with pure ground-glass opacity (GGO) areas on HRCT scans (p = 0.007). 18F-FDG PET/CT showed significant metabolic activity for all HRCT patterns. The correlation between serum CCL2 levels and GGO on HRCT scans suggests a central role of fibroblasts in these areas, adding new information towards the understanding of the mechanisms surrounding cellular and molecular elements and their expression on HRCT scans in patients with SSc-associated ILD. Conclusions: 18F-FDG PET/CT appears to be unable to differentiate the intensity of metabolic activity across HRCT patterns in chronic SSc patients. The association between CCL2 and GGO might be related to fibroblast activity in these areas; however, upregulated CCL2 expression in the lung tissue of SSc patients should be investigated in order to gain a better understanding of this association.

RESUMO Objetivo: Investigar a correlação entre achados de TCAR e a atividade metabólica pulmonar nas regiões correspondentes por meio de PET/TC com 18F-FDG e marcadores inflamatórios em pacientes com doença pulmonar intersticial (DPI) associada à esclerose sistêmica (ES). Métodos: Estudo transversal envolvendo 23 pacientes adultos com DPI associada à ES sem outras doenças do tecido conjuntivo. O estudo também envolveu PET/TC com 18F-FDG, TCAR, dosagem sérica de quimiocinas, dados clínicos e testes de função pulmonar. Resultados: Nessa coorte de pacientes com doença de longa duração (11,8 ± 8,7 anos), 19 (82,6%) apresentaram o padrão de pneumonia intersticial não específica. A mediana dos valores padronizados de captação foi maior nas áreas de faveolamento (1,95; p = 0,85). Os níveis séricos de soluble tumor necrosis factor receptor 1, soluble tumor necrosis factor receptor 2, C-C motif chemokine ligand 2 (CCL2) e C-X-C motif chemokine ligand 10 foram maiores nos pacientes com ES que nos controles. Os níveis séricos de CCL2 - um marcador de atividade fibroblástica - correlacionaram-se com áreas de opacidade em vidro fosco (OVF) pura na TCAR (p = 0,007). A PET/TC com 18F-FDG mostrou atividade metabólica significativa para todos os padrões de TCAR. A correlação entre níveis séricos de CCL2 e OVF na TCAR sugere que os fibroblastos desempenham um papel fundamental nessas áreas, acrescentando novas informações para a compreensão dos mecanismos que envolvem elementos celulares e moleculares e sua expressão na TCAR em pacientes com DPI associada à ES. Conclusões: A PET/TC com 18F-FDG aparentemente não consegue diferenciar a intensidade da atividade metabólica nos diferentes padrões de TCAR em pacientes com ES crônica. A associação entre CCL2 e OVF pode estar relacionada à atividade fibroblástica nessas áreas; entretanto, a expressão suprarregulada de CCL2 no tecido pulmonar de pacientes com ES deve ser investigada para que se compreenda melhor essa associação.

Effects of Short Term Metformin Treatment on Brown Adipose Tissue Activity and Plasma Irisin Levels in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.

Polycystic ovary syndrome (PCOS) is a chronic dysfunction associated with obesity and metabolic disorders that can be ameliorated by treatment with metformin. Brown adipose tissue (BAT) has been recently identified in adult humans, and irisin is a myokine that induces BAT formation. The aim of this randomized controlled trial was to evaluate whether a short term treatment with metformin alters BAT activity and plasma irisin levels in women with PCOS. The participants were randomly assigned to receive metformin (1500 mg/day, n=21) or placebo (n=24) during 60 days. BAT activity was assessed by 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by enzyme immunoassay. The groups were similar in age, body measures, metabolic profile and PCOS phenotypes. BAT activity did not change significantly in the women treated with metformin (median Δ SUVmax=-0.06 g/ml, interquartile interval -2.81 to 0.24 g/ml, p=0.484, Wilcoxon's test) or placebo (median Δ SUVmax=0.98 g/ml, interquartile interval -2.94 to 4.60 g/ml, p=0.386). In addition, plasma irisin levels remained unchanged in the groups treated with metformin (median Δ=-98 ng/ml, interquartile interval -366 to 60 ng/ml, p=0.310) and placebo (median Δ=28 ng/ml, interquartile interval -1260 to 215 ng/ml, p=0.650). These results suggest that in PCOS women BAT activity and plasma irisin levels may not change after a brief treatment with metformin.

Brown adipose tissue activity is reduced in women with polycystic ovary syndrome.

Objective: To evaluate whether brown adipose tissue (BAT) activity is altered in women with polycystic ovary syndrome (PCOS), and whether BAT activity correlates with plasma levels of irisin, a myokine that can induce BAT formation. Design: We performed a cross-sectional study including women with PCOS (n = 45) and a healthy control group (n = 25) matched by age and body mass index (BMI). Methods: BAT activity was measured using 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by a validated enzyme immunoassay. Results: Total BAT activity was significantly reduced in women with PCOS (maximal standardized uptake value (SUVmax): median 7.4 g/mL, interquartile range 0.9-15.4) compared to controls (median 13.0 g/mL, interquartile range 4.7-18.4, P = 0.047). However, this difference was no longer significant after adjustment for waist circumference, a surrogate marker of central adiposity. In the PCOS group, BAT activity correlated negatively with BMI (Spearman's r = -0.630, P = 0.000) and waist circumference (r = -0.592, P = 0.000) but not with plasma irisin levels. Conclusions: BAT activity was reduced in women with PCOS possibly due to increased central adiposity. In PCOS women, BAT activity did not correlate with plasma irisin levels.

18F-FDG PET/CT as a prognostic factor in penile cancer.

PURPOSE: Penile cancer (PC) is a rare neoplasm with an aggressive behavior and variable prognosis. Lymph node (LN) involvement and pathological features of the primary lesion have been proven to be the most important survival factors. Positron emission tomography/computed tomography with fluorodeoxyglucose labelled with fluorine-18 (18F-FDG PET/CT) provides information on tumor staging and works as a prognostic factor, with promising results in other carcinomas. The aim of the present study is to evaluate PET/CT as a prognostic factor in PC. METHODS: Fifty-five patients (mean age 56.6 y) diagnosed with penile squamous cell carcinoma were prospectively evaluated from 2012 to 2014. All subjects underwent 18F-FDG PET/CT before treatment and were regularly followed after surgery. RESULTS: Out of the 53 patients selected, 17 (32.1%) had localized disease (cT1-2) and 24 (45.3%) had palpable nodes (cN+). Partial penile amputation was performed in 38 patients (71.7%) and inguinal lymphadenectomy (LND) in 30 (56.6%). From the LND group, 16 (53.3%) presented with positive neoplastic cells (pN+). Patients with more aggressive disease had a significantly (p = 0.019) higher 18F-FDG tumor uptake (pSUVmax), while inguinal LN uptake (nSUVmax) was able to recognize metastatic LN (p = 0.039). Some pathological prognostic features, when presented, have shown significant changes in pSUVmax values. Receiver operating characteristic (ROC) curves were performed and specific cutoff values of pSUVmax were evaluated to determine sensitivity and specificity. Regarding regional LNs, PET/CT presented a 76.2% accuracy in cN+ patients. After a 39-month follow up, pSUVmax of 16.6 (p = 0.0001) and nSUVmax of 6.5 (p = 0.019) were established as the ideal values to predict cancer-specific survival. The multivariate analysis confirmed nSUVmax as a predictor for LN metastasis (p = 0.043) and pSUVmax as a mean to estimate survival rate (p = 0.05). CONCLUSION: This study showed promising results on the use of 18F-FDG PET/CT as a prognostic tool for PC, using specific cutoff values of pSUVmax and nSUVmax.

Raman spectroscopy with a 1064-nm wavelength laser as a potential molecular tool for prostate cancer diagnosis: a pilot study.

Raman spectroscopy is widely used to investigate the structure and property of the molecules from their vibrational transitions and may allow for the diagnosis of cancer in a fast, objective, and nondestructive manner. This experimental study aims to propose the use of the 1064-nm wavelength laser in a Raman spectroscopy and to evaluate its discrimination capability in prostate cancer diagnosis. Seventy-four spectra from patients who underwent radical prostatectomy were evaluated. The acquired signals were filtered, normalized, and corrected for possible oscillations in the laser intensity and fluorescence effects. Wilcoxon tests revealed significant differences between the benign and malign samples associated with the deformation vibration characteristic of nucleic acids, proteins, and lipids. A classifier based on support vector machines was able to predict the Gleason scores of the samples with 95% of accuracy, opening a perspective for the use of the 1064-nm excitatory wavelength in prostatic cancer diagnosis.

Use of machine learning to predict cognitive performance based on brain metabolism in Neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) can cause a wide range of cognitive deficits, but its underlying nature is still unknown. We investigated the correlation between cognitive performance and specific patterns of resting-state brain metabolism in a NF1 sample. Sixteen individuals diagnosed with NF1 underwent 18F-FDG PET/CT brain imaging followed by a neuropsychological assessment. Principal component analysis was performed on 17 measures of cognitive function and a machine learning approach based on Gaussian Process Regression was used to individually predict the components that represented most of the variance in the neuropsychological data. The accuracy of the method was estimated using leave-one-out cross-validation and its significance through permutation testing. We found that only the first component could be accurately predicted from resting state metabolism (r = 0.926, p<0.001). Multiple and heterogeneous measures contribute to the first component, mainly WISC/WAIS Procedure and Verbal IQ, verbal memory and fluency. Considering the accurate prediction of measures of neuropsychological performance based on brain metabolism in NF1 patients, this suggests an underlying metabolic pattern that relates to cognitive performance in this group.

Spinal cord hypometabolism associated with infection by human T-cell lymphotropic virus type 1(HTLV-1).

BACKGROUND: HTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals. METHODOLOGY: This is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF). PRINCIPAL FINDINGS: 18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model. CONCLUSIONS: 18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP. SIGNIFICANCE: Our findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls.

Individualized threshold for tumor segmentation in 18F-FDG PET/CT imaging: The key for response evaluation of neoadjuvant chemoradiation therapy in patients with rectal cancer?

INTRODUCTION: The standard treatment for locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiation followed by radical surgery. Regardless the extensive use of SUVmax in 18F-FDG PET tumor uptake as representation of tumor glycolytic consumption, there is a trend to apply metabolic volume instead. Thus, the aim of the present study was to evaluate a noninvasive method for tumor segmentation using the 18F-FDG PET imaging in order to predict response to neoadjuvant chemoradiation therapy in patients with rectal cancer. METHOD: The sample consisted of stage II and III rectal cancer patients undergoing 18F-FDG PET/CT examination before and eight weeks after neoadjuvant therapy. An individualized tumor segmentation methodology was applied to generate tumor volumes (SUV2SD) and compare with standard SUVmax and fixed threshold (SUV40%, SUV50% and SUV60%) pre- and post-therapy. Therapeutic response was assessed in the resected specimens using Dworak's protocol recommendations. Several variables were generated and compared with the histopathological results. RESULTS: Seventeen (17) patients were included and analyzed. Significant differences were observed between responders (Dworak 3 and 4) and non-responders for SUVmax-2 (p<0.01), SUV2SD-2 (p<0.05), SUV40%-2 (p<0.05), SUV50%-2 (p<0.05) and SUV60%-2 (p<0.05). ROC analyses showed significant areas under the curve (p<0.01) for the proposed methodology with sensitivity and specificity varying from 60% to 83% and 73% to 82%, respectively. CONCLUSION: The present study confirmed the predictive power of the variables using a noninvasive individualized methodology for tumor segmentation based on 18F-FDG PET/CT imaging for response evaluation in patients with rectal cancer after neoadjuvant chemoradiation therapy.

Individualized threshold for tumor segmentation in 18F-FDG PET/CT imaging: The key for response evaluation of neoadjuvant chemoradiation therapy in patients with rectal cancer? / Individualização na segmentação tumoral de imagens de 18F-FDG PET/CT: a chave para avaliação de resposta terapêutica neoadjuvante em pacientes com câncer retal?

Summary Introduction: The standard treatment for locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiation followed by radical surgery. Regardless the extensive use of SUVmax in 18F-FDG PET tumor uptake as representation of tumor glycolytic consumption, there is a trend to apply metabolic volume instead. Thus, the aim of the present study was to evaluate a noninvasive method for tumor segmentation using the 18F-FDG PET imaging in order to predict response to neoadjuvant chemoradiation therapy in patients with rectal cancer. Method: The sample consisted of stage II and III rectal cancer patients undergoing 18F-FDG PET/CT examination before and eight weeks after neoadjuvant therapy. An individualized tumor segmentation methodology was applied to generate tumor volumes (SUV2SD) and compare with standard SUVmax and fixed threshold (SUV40%, SUV50% and SUV60%) pre- and post-therapy. Therapeutic response was assessed in the resected specimens using Dworak's protocol recommendations. Several variables were generated and compared with the histopathological results. Results: Seventeen (17) patients were included and analyzed. Significant differences were observed between responders (Dworak 3 and 4) and non-responders for SUVmax-2 (p<0.01), SUV2SD-2 (p<0.05), SUV40%-2 (p<0.05), SUV50%-2 (p<0.05) and SUV60%-2 (p<0.05). ROC analyses showed significant areas under the curve (p<0.01) for the proposed methodology with sensitivity and specificity varying from 60% to 83% and 73% to 82%, respectively. Conclusion: The present study confirmed the predictive power of the variables using a noninvasive individualized methodology for tumor segmentation based on 18F-FDG PET/CT imaging for response evaluation in patients with rectal cancer after neoadjuvant chemoradiation therapy.

Resumo Introdução: O câncer retal (RC) é uma doença de importância global, e o tratamento padrão para o câncer retal localmente avançado compreende quimiorradiação neoadjuvante seguida de cirurgia radical. Independentemente do uso extensivo da captação tumoral mais intensa do 18F-FDG (conhecida como SUVmax) como representativo do consumo glicolítico do tumor nas imagens de PET, há uma tendência para aplicar volume metabólico. Dessa forma, o objetivo do presente estudo foi avaliar um método não invasivo de segmentação tumoral utilizando a 18F-FDG PET para predizer a resposta à quimiorradioterapia neoadjuvante em pacientes com câncer de reto. Método: A amostra consistiu em pacientes com câncer retal em estádios II e III submetidos ao exame de 18F-FDG PET/CT antes e oito semanas após a terapia neoadjuvante. Foi aplicada uma metodologia de segmentação tumoral individualizada para gerar volumes tumorais (SUV2SD). A resposta terapêutica foi avaliada nos espécimes ressecados utilizando as recomendações do protocolo de Dworak. Várias variáveis foram geradas e comparadas com os resultados histopatológicos. Resultados: Dezessete (17) pacientes foram incluídos e analisados. Foram observadas diferenças significativas entre os respondedores (Dworak 3 e 4) e não respondedores para SUVmax-2 (p<0,01), SUV2SD-2 (p<0,05), SUV40%-2 (p<0,05), SUV50%-2 (p<0,05) e SUV60%-2 (p< 0,05). As análises ROC mostraram áreas significativas sob a curva (p<0,01) para a metodologia proposta, com sensibilidade e especificidade variando de 60% a 83% e 73% a 82%, respectivamente. Conclusão: O presente estudo confirmou o poder preditivo das variáveis utilizando uma metodologia não invasiva individualizada para segmentação tumoral baseada em imagens 18F-FDG PET/CT para avaliação da resposta em pacientes com câncer retal após tratamento com quimiorradiação neoadjuvante.

Targeting personalized medicine in a non-Hodgkin lymphoma patient with 18F-FDG and 18F-choline PET/CT.

Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT) with fluordeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 (18F-FDG) has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, 18F-FDG has shown false-positive uptake due to inflammatory reaction after chemo and/or radiation therapy. In this case report, we present a NHL patient evaluated with 18F-FDG and 18F-choline PET/CT scan imaging pre- and post-therapy. 18F-FDG and 18F-choline PET/CT were performed for the purpose of tumor staging and have shown intense uptake in infiltrative tissue as well as in the lymph node, but with some mismatching in the tumor. Post-treatment 18F-FDG and 18F-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. 18F-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-18F-FDG tracer can be used for targeted therapy and patient management.

DEB TACE for Intermediate and advanced HCC - Initial Experience in a Brazilian Cancer Center.

BACKGROUND: According to Barcelona Clinic Liver Cancer classification transarterial chemoembolization is indicated in patients with Hepatocellular Carcinoma in the intermediate stage. Drug-eluting microspheres can absorb and release the chemotherapeutic agent slowly for 14 days after its intra-arterial administration. This type of transarterial chemoembolization approach appears to provide at least equivalent effectiveness with less toxicity. METHODS: This is a prospective, single-center study, which evaluated 21 patients with intermediate and advanced hepatocellular carcinoma who underwent transarterial chemoembolization with drug-eluting microspheres. The follow up period was 2 years. Inclusion criteria was Child-Pugh A or B liver disease patients, intermediate or advanced hepatocellular carcinoma and performance status equal or below 2. Transarterial chemoembolization with drug-eluting microspheres was performed at 2-month intervals during the first two sessions. The third and subsequent sessions were performed according to the image findings on follow-up, on a "demand schedule". Tumor response and time to progression were evaluated along the two-year follow up period. RESULTS: Of the 21 patients 90% presented with liver cirrhosis, 62% had Barcelona Clinic Liver Cancer stage B and 38% had Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma. Average tumor size was 6.9 cm. The average number of Transarterial chemoembolization with drug-eluting microspheres procedures was 3 with a total of 64 sessions. The predominant toxicity was mild. Liver function was not significantly affected in most patients. Two deaths occurred within 90 days after Transarterial chemoembolization with drug-eluting microspheres (ischemic hepatitis and hydropic decompensation). Technical success was achieved in 63 of 64 procedures. The mean hospital stay was 1.5 days. The progression free and overall survival at 1 and 2 years were 73.0% and 37.1%, 73.7% and 41.6%, respectively. CONCLUSION: Transarterial chemoembolization with drug-eluting microspheres is able to deliver significant tumor response and progression free survival rate with acceptable toxicity. Larger studies are needed to identify exactly which subset of advanced hepatocellular patients may benefit from this treatment. TRIAL REGISTRATION: study ID ISRCTN16295622. Registered October 14th 2016. Retrospectively registered. Website registration: http://www.isrctn.com/ISRCTN16295622.

Targeting personalized medicine in a non-Hodgkin lymphoma patient with 18F-FDG and 18F-choline PET/CT

Summary Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT) with fluordeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 (18F-FDG) has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, 18F-FDG has shown false-positive uptake due to inflammatory reaction after chemo and/or radiation therapy. In this case report, we present a NHL patient evaluated with 18F-FDG and 18F-choline PET/CT scan imaging pre- and post-therapy. 18F-FDG and 18F-choline PET/CT were performed for the purpose of tumor staging and have shown intense uptake in infiltrative tissue as well as in the lymph node, but with some mismatching in the tumor. Post-treatment 18F-FDG and 18F-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. 18F-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-18F-FDG tracer can be used for targeted therapy and patient management.

Ambient radiation levels in positron emission tomography/computed tomography (PET/CT) imaging center.

OBJECTIVE: To evaluate the level of ambient radiation in a PET/CT center. MATERIALS AND METHODS: Previously selected and calibrated TLD-100H thermoluminescent dosimeters were utilized to measure room radiation levels. During 32 days, the detectors were placed in several strategically selected points inside the PET/CT center and in adjacent buildings. After the exposure period the dosimeters were collected and processed to determine the radiation level. RESULTS: In none of the points selected for measurements the values exceeded the radiation dose threshold for controlled area (5 mSv/year) or free area (0.5 mSv/year) as recommended by the Brazilian regulations. CONCLUSION: In the present study the authors demonstrated that the whole shielding system is appropriate and, consequently, the workers are exposed to doses below the threshold established by Brazilian standards, provided the radiation protection standards are followed.

OBJETIVO: Avaliar o nível de radiação no ambiente de um serviço de PET/CT. MATERIAIS E MÉTODOS: Para a determinação dos níveis de radiação no ambiente foram utilizados dosímetros termoluminescentes TLD-100H previamente selecionados e calibrados. Estes detectores foram expostos durante 32 dias em diversos pontos estrategicamente escolhidos nas dependências do serviço e nos prédios adjacentes. Após o período de exposição, os dosímetros foram recolhidos e processados. RESULTADOS: Em nenhum dos pontos avaliados os valores medidos ultrapassaram os limites de restrição de dose para área controlada (5 mSv/ano) ou para área livre (0,5 mSv/ano) recomendados pelas normas brasileiras. CONCLUSÃO: Com este trabalho foi possível demonstrar que todas as blindagens do serviço estão adequadas e que, consequentemente, os trabalhadores, desde que seguindo as normas de radioproteção, receberão doses abaixo da dose de restrição indicada no Brasil.

Malignant phenotype and two SDHD mutations in a family with paraganglioma syndrome type 1.

BACKGROUND: Paraganglioma syndrome type 1 (PGL1) is a rare autosomal dominant syndrome associated with multiple, overwhelmingly benign, pheochromocytomas and paragangliomas, attributed to SDHD gene mutations. OBJECTIVE: Clinically and molecularly characterize a family with uncommon malignant phenotype of paragangliomas attributed to two seemingly pathogenic SDHD germline mutations. MATERIALS & METHODS: The proband presented with large bilateral carotid body tumours and family history of cervical masses in his five siblings. All family members underwent clinical examination, imaging studies (18F-FDG PET/CT) and genotyping of relevant genes. The proband was diagnosed with locally advanced paraganglioma; his hypertensive, otherwise asymptomatic father, had locally advanced pheochromocytoma and his three siblings showed multiple head and neck masses, confirmed to be paragangliomas with local metastasis. All affected patients carried two germline mutations in the SDHD gene; a previously reported nonsense mutation in exon 1 (p.Trp5X) and a novel missense mutation in exon 2 (p.Pro53Leu), highly deleterious by in silico analysis. Allelic loss at the SDHD locus was not shown for any of the analysed tumours. CONCLUSIONS: This is a rare case of malignant PGL1 with seemingly double pathogenic mutations in the SDHD gene, highlighting the possibility that the presence of both mutations is associated with the more aggressive phenotype.

Ambient radiation levels in positron emission tomography/computed tomography (PET/CT) imaging center / Níveis de radiação ambiental em serviço de tomografia por emissão de pósitrons acoplada a tomografia computadorizada (PET/CT)

Objective: To evaluate the level of ambient radiation in a PET/CT center. Materials and Methods: Previously selected and calibrated TLD-100H thermoluminescent dosimeters were utilized to measure room radiation levels. During 32 days, the detectors were placed in several strategically selected points inside the PET/CT center and in adjacent buildings. After the exposure period the dosimeters were collected and processed to determine the radiation level. Results: In none of the points selected for measurements the values exceeded the radiation dose threshold for controlled area (5 mSv/year) or free area (0.5 mSv/year) as recommended by the Brazilian regulations. Conclusion: In the present study the authors demonstrated that the whole shielding system is appropriate and, consequently, the workers are exposed to doses below the threshold established by Brazilian standards, provided the radiation protection standards are followed. .

Objetivo: Avaliar o nível de radiação no ambiente de um serviço de PET/CT. Materiais e Métodos: Para a determinação dos níveis de radiação no ambiente foram utilizados dosímetros termoluminescentes TLD-100H previamente selecionados e calibrados. Estes detectores foram expostos durante 32 dias em diversos pontos estrategicamente escolhidos nas dependências do serviço e nos prédios adjacentes. Após o período de exposição, os dosímetros foram recolhidos e processados. Resultados: Em nenhum dos pontos avaliados os valores medidos ultrapassaram os limites de restrição de dose para área controlada (5 mSv/ano) ou para área livre (0,5 mSv/ano) recomendados pelas normas brasileiras. Conclusão: Com este trabalho foi possível demonstrar que todas as blindagens do serviço estão adequadas e que, consequentemente, os trabalhadores, desde que seguindo as normas de radioproteção, receberão doses abaixo da dose de restrição indicada no Brasil. .

Dosimetria de pacientes submetidos a exames de PET/CT cerebral para diagnóstico de comprometimento cognitivo leve / Dosimetry of patients submitted to cerebral PET/CT for the diagnosis of mild cognitive impairment

Objetivo: O objetivo deste trabalho é avaliar a dose em pacientes submetidos a PET/CT para diagnóstico de comprometimento cognitivo leve. Materiais e Métodos: Para as medidas da dose absorvida proveniente da modalidade CT utilizaram-se detectores TLD-100 inseridos em um simulador Alderson Rando®. Os simuladores antropomórficos (versões masculina e feminina) foram submetidos aos mesmos protocolos técnicos para aquisição das imagens dos pacientes. A dose absorvida resultante da injeção do radiofármaco foi estimada por meio do modelo proposto pela ICRP 106. Resultados: A dose efetiva a que foram submetidos os pacientes com esta técnica diagnóstica foi, aproximadamente, (5,34 ± 1,99) mSv. Conclusão: Protocolos otimizados para cálculo de atividade radioativa que será injetada em cada paciente podem contribuir para a redução da dose efetiva nos pacientes durante a realização do diagnóstico de comprometimento cognitivo leve com PET/CT. .

Objective: The present study was aimed at evaluating the effective radiation dose in patients submitted to PET/CT for the diagnosis of mild cognitive impairment. Materials and Methods: TLD-100 detectors inserted into an Alderson Rando® anthropomorphic phantom were utilized to measure the absorbed dose coming from the CT imaging modality. The anthropomorphic phantoms (male and female adult versions) were submitted to the same technical protocols for patients’ images acquisition. The absorbed dose resulting from the radiopharmaceutical injection was estimated by means of the model proposed by the ICRP publication 106. Results: The effective dose in patients submitted to this diagnostic technique was approximately (5.34 ± 1.99) mSv. Conclusion: Optimized protocols for calculation of radioactive activity injected into patients submitted to this diagnostic technique might contribute to reduce the effective radiation dose resulting from PET/CT in the diagnosis of mild cognitive impairment. .

Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer.

BACKGROUND: Cisplatin-based chemoradiation (CRT) is the standard treatment for patients with locally advanced cervical cancer. Epidermal growth factor receptor (EGFR) is frequently overexpressed in cervical cancer, and EGFR inhibition itself has antitumor effects and potentiates CRT. Results of a previous phase 1 trial of the EGFR inhibitor erlotinib combined with cisplatin-based CRT (E + CRT) recommended a phase 2 erlotinib dose of 150 mg/day. METHODS: Eligibility criteria included International Federation of Gynecology and Obstetrics stage IIB to IIIB epidermoid cervical cancer, no prior therapy, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received erlotinib at a dose of 150 mg/day 1 week before and in combination with cisplatin (40 mg/m(2) administered weekly for 5 cycles) and radiotherapy (4500 centigrays in 25 fractions), followed by brachytherapy (4 fractions at a dose of 600 centigrays weekly). RESULTS: A total of 36 patients completed treatment with E + CRT. The median duration of therapy was 77 days and the median follow-up period was 59.3 months. The therapy was well tolerated overall, and 34 patients (94.4%) achieved a complete response. The 2-year and 3-year cumulative overall and progression-free survival rates were 91.7% and 80.6% and 80% and 73.8%, respectively. CONCLUSIONS: Treatment with E + CRT appears to be safe and exerts significant activity against locally advanced cervical cancer. To the best of the authors' knowledge, this is the first study to date to demonstrate that a target agent has promising activity against locally advanced cervical cancer.

Dosimetry of patients submitted to cerebral PET/CT for the diagnosis of mild cognitive impairment.

OBJECTIVE: The present study was aimed at evaluating the effective radiation dose in patients submitted to PET/CT for the diagnosis of mild cognitive impairment. MATERIALS AND METHODS: TLD-100 detectors inserted into an Alderson Rando® anthropomorphic phantom were utilized to measure the absorbed dose coming from the CT imaging modality. The anthropomorphic phantoms (male and female adult versions) were submitted to the same technical protocols for patients' images acquisition. The absorbed dose resulting from the radiopharmaceutical injection was estimated by means of the model proposed by the ICRP publication 106. RESULTS: The effective dose in patients submitted to this diagnostic technique was approximately (5.34 ± 1.99) mSv. CONCLUSION: Optimized protocols for calculation of radioactive activity injected into patients submitted to this diagnostic technique might contribute to reduce the effective radiation dose resulting from PET/CT in the diagnosis of mild cognitive impairment.

OBJETIVO: O objetivo deste trabalho é avaliar a dose em pacientes submetidos a PET/CT para diagnóstico de comprometimento cognitivo leve. MATERIAIS E MÉTODOS: Para as medidas da dose absorvida proveniente da modalidade CT utilizaram-se detectores TLD-100 inseridos em um simulador Alderson Rando®. Os simuladores antropomórficos (versões masculina e feminina) foram submetidos aos mesmos protocolos técnicos para aquisição das imagens dos pacientes. A dose absorvida resultante da injeção do radiofármaco foi estimada por meio do modelo proposto pela ICRP 106. RESULTADOS: A dose efetiva a que foram submetidos os pacientes com esta técnica diagnóstica foi, aproximadamente, (5,34 ± 1,99) mSv. CONCLUSÃO: Protocolos otimizados para cálculo de atividade radioativa que será injetada em cada paciente podem contribuir para a redução da dose efetiva nos pacientes durante a realização do diagnóstico de comprometimento cognitivo leve com PET/CT.