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Here, we report on the added value of principal component analysis applied to a dataset of texture features derived from 39 solitary pulmonary lung nodule (SPN) lesions for the purpose of differentiating benign from malignant lesions, as compared to the use of SUVmax alone. Texture features were derived using the LIFEx software. The eight best-performing first-, second-, and higher-order features for separating benign from malignant nodules, in addition to SUVmax (MaximumGreyLevelSUVbwIBSI184IY), were included for PCA. Two principal components (PCs) were retained, of which the contributions to the total variance were, respectively, 87.6% and 10.8%. When included in a logistic binomial regression analysis, including age and gender as covariates, both PCs proved to be significant predictors for the underlying benign or malignant character of the lesions under study (p = 0.009 for the first PC and 0.020 for the second PC). As opposed to SUVmax alone, which allowed for the accurate classification of 69% of the lesions, the regression model including both PCs allowed for the accurate classification of 77% of the lesions. PCs derived from PCA applied on selected texture features may allow for more accurate characterization of SPN when compared to SUVmax alone.
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Hypoxia leads to changes in tumor microenvironment (upregulated CAFs) with resultant aggressiveness. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1α). [68Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types. We hypothesized that [68Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1α expression. The [68Ga]Ga-FAPI PET/CT scans of women with cancer of the cervix were reviewed and the maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. Correlation analysis was performed between PET-derived parameters and immunohistochemical staining as well as between PET-derived parameters and the presence of metastasis. Ten women were included. All patients demonstrated tracer uptake in the primary site or region of the primary. All patients had lymph node metastases while only six patients had distant visceral or skeletal metastases. The mean SUVmax, SUVmean, and FAPI-TV was 18.89, 6.88, and 195.66 cm3, respectively. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1α expression in all tested samples. There was a positive correlation between the presence of skeletal metastases and staining for HIF-1α (r=0.80;p=0.017). The presence of skeletal metastasis was correlated to the HIF-1⺠staining (percentage distribution). Furthermore, the FAPI-TV was a better predictor of metastatic disease than the SUVmax.
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PURPOSE: 225Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following 225Ac-PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment and are seeking alternative therapies. Thus, we report our preliminary findings in a retrospective series of 21 mHSPC patients that refused standard treatment options and were treated with 225Ac-PSMA-617. METHODS: We retrospectively reviewed patients with histologically confirmed de novo treatment-naïve bone ± visceral mHSPC that were treated with 225Ac-PSMA-617 radioligand therapy (RLT). Inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, treatment-naive bone ± visceral mHSPC, and patients refusal for ADT ± docetaxel, abiraterone acetate, or enzalutamide. We evaluated the response to treatment using prostate-specific antigen (PSA) response and the progression-free survival (PFS) and overall survival (OS) as well as the toxicities. RESULTS: Twenty-one mHSPC patients were included in this preliminary work. Following treatment, twenty patients (95%) had any decline in PSA and eighteen patients (86%) presented with a PSA decline of ≥ 50% including 4 patients in whom PSA became undetectable. A lower percentage decrease in PSA following treatment was associated with increased mortality and shorter progression-free survival. Overall, administration of 225Ac-PSMA-617 was well tolerated. The commonest toxicity seen was grade I/II dry mouth observed in 94% of patients. CONCLUSIONS: Given these favorable results, randomized prospective multicenter trials assessing the clinical value of 225Ac-PSMA-617 as a therapeutic agent for mHSPC administered either as monotherapy or administered concomitant with ADT are of interest.
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Carcinoma , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Estudos Prospectivos , Próstata/patologia , Antígeno Prostático Específico/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The clinical utility of radiomics is hampered by a high correlation between the large number of features analysed which may result in the "bouncing beta" phenomenon which could in part explain why in a similar patient population texture features identified and/or cut-off values of prognostic significance differ from one study to another. Principal component analysis (PCA) is a technique for reducing the dimensionality of large datasets containing highly correlated variables, such as texture feature datasets derived from FDG PET images, increasing data interpretability whilst at the same time minimizing information loss by creating new uncorrelated variables that successively maximize variance. Here, we report on PCA of a texture feature dataset derived from 123 malignant melanoma lesions with a significant range in lesion size using the freely available LIFEx software. RESULTS: Thirty-eight features were derived from all lesions. All features were standardized. The statistical assumptions for carrying out PCA analysis were met. Seven principal components with an eigenvalue > 1 were identified. Based on the "elbow sign" of the Scree plot, only the first five were retained. The contribution to the total variance of these components derived using Varimax rotation was, respectively, 30.6%, 23.6%, 16.1%, 7.4% and 4.1%. The components provided summarized information on the locoregional FDG distribution with an emphasis on high FDG uptake regions, contrast in FDG uptake values (steepness), tumour volume, locoregional FDG distribution with an emphasis on low FDG uptake regions and on the rapidity of changes in SUV intensity between different regions. CONCLUSIONS: PCA allowed to reduce the dataset of 38 features to a set of 5 uncorrelated new variables explaining approximately 82% of the total variance contained within the dataset. These principal components may prove more useful for multiple regression analysis considering the relatively low numbers of patients usually included in clinical trials on FDG PET texture analysis. Studies assessing the superior differential diagnostic, predictive or prognostic value of principal components derived using PCA as opposed to the initial texture features in clinical relevant settings are warranted.
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BACKGROUND: Colorectal cancer, one of the most common malignancies worldwide, is associated with a high mortality rate, mainly caused by metastasis. Comparative metagenome-wide association analyses of healthy individuals and cancer patients suggest a role for the human intestinal microbiota in tumor progression. However, the microbial molecules involved in host-microbe communication are largely unknown, with current studies mainly focusing on short-chain fatty acids and amino acid metabolites as potential mediators. Quorum sensing peptides are not yet considered in this context since their presence in vivo and their ability to affect host cells have not been reported so far. RESULTS: Here, we show that EntF*, a metabolite of the quorum sensing peptide EntF produced by Enterococcus faecium, is naturally present in mice bloodstream. Moreover, by using an orthotopic mouse model, we show that EntF* promotes colorectal cancer metastasis in vivo, with metastatic lesions in liver and lung tissues. In vitro tests suggest that EntF* regulates E-cadherin expression and consequently the epithelial-mesenchymal transition, via the CXCR4 receptor. In addition, alanine-scanning analysis indicates that the first, second, sixth, and tenth amino acid of EntF* are critical for epithelial-mesenchymal transition and tumor metastasis. CONCLUSION: Our work identifies a new class of molecules, quorum sensing peptides, as potential regulators of host-microbe interactions. We prove, for the first time, the presence of a selected quorum sensing peptide metabolite in a mouse model, and we demonstrate its effects on colorectal cancer metastasis. We believe that our work represents a starting point for future investigations on the role of microbiome in colorectal cancer metastasis and for the development of novel bio-therapeutics in other disease areas.
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Neoplasias Colorretais , Microbiota , Aminoácidos , Animais , Humanos , Camundongos , Microbiota/fisiologia , Peptídeos , Percepção de Quorum/fisiologiaRESUMO
Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings.
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AIM: The prostate bed is one of the common sites of early recurrence of prostate cancer. The currently used PSMA ligands (68Ga-PSMA-11 and 99mTc-PSMA) undergo early urinary clearance resulting in interfering physiological activity within and surrounding the prostate. This can result in sites of cancer recurrence being obscured. 18F-PSMA-1007 has an advantage of delayed urinary clearance thus the prostate region is reviewed without any interfering physiological activity. The aim of this study was to determine the diagnostic performance of 18F-PSMA-1007 PET/CT in patients with early biochemical recurrence after definitive therapy. METHODS: Forty-six Prostate cancer (mean age 66.7±7.5, range 48-87 years) presenting with biochemical recurrence (median PSA 1.6ng/ml, range 0.1-10.0) underwent non-contrast-enhanced 18F-PSMA-1007 PET/CT. PET/CT findings were evaluated qualitatively and semiquantitatively (SUVmax) and compared to the results of histology, Gleason grade, and conventional imaging. RESULTS: Twenty-four of the 46 (52.2%) patients demonstrated a site of recurrence on 18F-PSMA-1007 PET/CT. Oligometastatic disease was detected in 15 (32.6%) of these patients. Of these 10 (37.5%) demonstrated intra-prostatic recurrence, lymph node disease was noted in 11 (45.8%) whilst two patients demonstrated skeletal metastases. The detection rates for PSA levels 0-<0.5, 0.5-<1, 1-2, >2 were 31.3%, 33.3%, 55.6% and 72.2% respectively. 7 (29.2%) of the positive patients had been described as negative or equivocal on conventional imaging. An optimal PSA cut-off level of 1.3ng/ml was found. CONCLUSION: 18F-PSMA-1007 demonstrated good diagnostic performance detecting sites of recurrence. Its ability to detect sites of recurrence in the setting of early biochemical recurrence will have a significant impact on patient management.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Idoso , Idoso de 80 Anos ou mais , Ácido Edético , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Niacinamida/análogos & derivados , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Compostos RadiofarmacêuticosRESUMO
Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years 68Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with 68Ga-Nitroimidazole derivative and the correlation with 18F-FDG PET/CT and immunohistochemistry. Twenty women with cervical cancer underwent both 18F-FDG and 68Ga-Nitroimidazole PET/CT imaging. Dual-point imaging was performed for 68Ga-Nitroimidazole PET. Immunohistochemical analysis was performed with hypoxia inducible factor-1α (HIF-1α). We documented SUVmax, SUVmean of the primary lesions as well as tumor to muscle ratio (TMR), tumor to blood (TBR), metabolic tumor volume (MTV) and hypoxic tumor volume (HTV). There was no significant difference in the uptake of 68Ga-Nitroimidazole between early and delayed imaging. Twelve patients had uptake on 68Ga-Nitroimidazole PET. Ten patients demonstrated varying intensities of HIF-1α expression and six of these also had uptake on 68Ga-Nitroimidazole PET. We found a strong negative correlation between HTV and immunohistochemical staining (r = -0.660; p = 0.019). There was no correlation between uptake on PET imaging and immunohistochemical analysis with HIF-1α. Two-thirds of the patients demonstrated hypoxia on 68Ga-Nitroimidazole PET imaging.
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BACKGROUND: To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by 18F-FDG-PET/CT. METHODS: We reviewed the 18F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the 18F-FDG-PET/CT study. RESULTS: We studied 303 women including 112 HIV-infected patients. FIGO stage III disease was present in 131 patients. Of 198 patients with recurrence, 74 were HIV-infected while 124 were not (P=0.849). HIV infected patients were younger (41.99±9.30 years) compared to HIV-uninfected (50.19±11.09), P<0.001. Local recurrence was present in 125 patients while 100 patients had a distant recurrence. Recurrence occurred at a single site in 88 patients and two or more sites in 110 patients. No significant difference in the recurrent patterns between HIV-infected and uninfected patients. Median time to recurrence was 10.50 months (range: 6.00-156.00) among HIV-infected versus 12.00 months (IQR:7.00-312.00) among the uninfected, P=0.065. FIGO stage III (P=0.042) and the presence of histological sub-types other than SCC (P=0.005) were significant predictors of recurrence. HIV infection by itself was not significant in predicting recurrence (P=0.843). CONCLUSIONS: HIV infection has no significant impact on the rate, time or pattern of recurrence in women with suspected cervical carcinoma recurrence. Advanced disease and histological variant other than SCC are predictive of recurrence.
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Infecções por HIV , Neoplasias do Colo do Útero , Feminino , Fluordesoxiglucose F18 , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/epidemiologia , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologiaRESUMO
Lymphoma is the third most common paediatric cancer. Early detection of high-risk patients is necessary to anticipate those who require intensive therapy and follow-up. Current literature shows that residual tumor avidity on PET (Positron Emission Tomography) following chemotherapy corresponds with decreased survival. However, the value of metabolic parameters has not been adequately investigated. In this retrospective study, we aimed to evaluate the prognostic value of metabolic and other parameters in paediatric and adolescent Hodgkin lymphoma. We recorded tMTV (total Metabolic Tumor Volume), TLG (Total Lesion Glycolysis), and SUVmax (maximum Standard Uptake Value) on baseline PET, as well the presence of bone marrow or visceral involvement. HIV (human immunodeficiency virus) status and baseline biochemistry from clinical records were noted. All patients received stage-specific standard of care therapy. Response assessment on end-of-treatment PET was evaluated according to the Deauville criteria. We found that bone marrow involvement (p = 0.028), effusion (p < 0.001), and treatment response (p < 0.001) on baseline PET, as well as HIV status (p = 0.036) and baseline haemoglobin (p = 0.039), were significantly related to progression-free survival (PFS), whereas only effusion (p = 0.017) and treatment response (p = 0.050) were predictive of overall survival (OS). Only baseline tMTV predicted treatment response (p = 0.017). This confirms the value of F-18 FDG PET/CT (Fluoro-deoxy-glucose Positron Emission Tomography/Computed Tomography) in prognostication in paediatric and adolescent Hodgkin lymphoma; however, further studies are required to define the significance of metabolic parameters.
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While FDG PET/CT bears a high sensitivity and specificity for the staging of stage III and IV melanoma as well as for the purpose of melanoma recurrence detection, overall results tend to vary from one part of the body to another as well as for melanoma from cutaneous or choroidal origin. In this paper, organ or site-related differences in sensitivity and specificity in melanoma patients, both from cutaneous and choroidal origin, as well as their impact on clinical decision making are discussed. Furthermore, with the advent of immunotherapy for the treatment of malignant melanoma, post-treatment related potential false positive findings have emerged, the knowledge of which is essential for accurate treatment response assessment. These post-treatment related potential false positive findings are summarized in this paper so as to help the nuclear medicine physician in avoiding erroneous interpretation of acquired FDG PET/CT images in melanoma patients receiving immuntherapy.
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Fluordesoxiglucose F18 , Melanoma , Humanos , Melanoma/diagnóstico por imagem , Melanoma/patologia , Melanoma/terapia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
To date, a wide variety of potential PET-apoptosis imaging radiopharmaceuticals targeting apoptosis-induced cell membrane asymmetry and acidification, as well as caspase 3 activation (substrates and inhibitors) have been developed with the purpose of rapidly assessing the response to treatment in cancer patients. Many of these probes were shown to specifically bind to their apoptotic target in vitro and their uptake to be enhanced in the in vivo-xenografted tumours in mice treated by means of chemotherapy, however, to a significantly variable degree. This may, in part, relate to the tumour model used given the fact that different tumour cell lines bear a different sensitivity to a similar chemotherapeutic agent, to differences in the chemotherapeutic concentration and exposure time, as well as to the different timing of imaging performed post-treatment. The best validated cell membrane acidification and caspase 3 targeting radioligands, respectively 18F-ML-10 from the Aposense family and the radiolabelled caspase 3 substrate 18F-CP18, have also been injected in healthy individuals and shown to bear favourable dosimetric and safety characteristics. However, in contrast to, for instance, the 99mTc-HYNIC-Annexin V, neither of both tracers was taken up to a significant degree by the bone marrow in the healthy individuals under study. Removal of white and red blood cells from the bone marrow through apoptosis plays a major role in the maintenance of hematopoietic cell homeostasis. The major apoptotic population in normal bone marrow are immature erythroblasts. While an accurate estimate of the number of immature erythroblasts undergoing apoptosis is not feasible due to their unknown clearance rate, their number is likely substantial given the ineffective quote of the erythropoietic process described in healthy subjects. Thus, the clinical value of both 18F-ML-10 and 18F-CP18 for apoptosis imaging in cancer patients, as suggested by a small number of subsequent clinical phase I/II trials in patients suffering from primary or secondary brain malignancies using 18F-ML-10 and in an ongoing trial in patients suffering from cancer of the ovaries using 18F-CP18, remains to be proven and warrants further investigation.
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Apoptose , Proteínas de Neoplasias/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/uso terapêutico , Animais , Humanos , Oncologia , Compostos Radiofarmacêuticos/químicaAssuntos
Neoplasias da Mama , Compostos Organometálicos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Radioisótopos de Gálio , Humanos , Imunoterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos RadiofarmacêuticosRESUMO
Radiomics or textural feature extraction obtained from positron emission tomography (PET) images through complex mathematical models of the spatial relationship between multiple image voxels is currently emerging as a new tool for assessing intra-tumoral heterogeneity in medical imaging. In this paper, available literature on texture analysis using FDG PET imaging in patients suffering from tumors of the gastro-intestinal tract is reviewed. While texture analysis of FDG PET images appears clinically promising, due to the lack of technical specifications, a large variability in the implemented methodology used for texture analysis and lack of statistical robustness, at present, no firm conclusions can be drawn regarding the predictive or prognostic value of FDG PET texture analysis derived indices in patients suffering from gastro-enterologic tumors. In order to move forward in this field, a harmonized image acquisition and processing protocol as well as a harmonized protocol for texture analysis of tumor volumes, allowing multi-center studies excluding statistical biases should be considered. Furthermore, the complementary and additional value of CT-imaging, as part of the PET/CT imaging technique, warrants exploration.
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The use of prostate specific membrane antigen (PSMA) binding agents, labelled with diagnostic and therapeutic radio-isotopes is opening the potential for a new era of personalized management of prostate carcinoma. A wide variety of immunohistochemistry studies have shown PSMA also to be upregulated on the endothelial cells of the neovasculature of a wide variety of other solid tumors where it may facilitate endothelial cell sprouting and invasion through its regulation of lytic proteases that have the ability to cleave the extracellular matrix. Similar to the introduction of PSMA-targeting theranostics in prostate carcinoma, overexpression of PSMA on newly formed tumor vessels may serve as a target for imaging and subsequent treatment of cancer through the use of agents that are capable of blocking PSMA in its function or through PSMA-mediated delivery of chemotherapeutics or radiation agents. In this review, the available data on PSMA expression on tumor neovasculature in human solid tumors assessed by using immunohistochemistry are discussed.
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Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Neoplasias/irrigação sanguínea , Neovascularização Patológica/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Patológica/patologiaRESUMO
Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225Ac-PSMA-617 treatment. Methods:225Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostate-specific antigen (PSA) was obtained for PSA response assessment. Results: Seventy-three men (mean age, 69 y; range, 45-85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1-17.4) and 18 mo (95% CI, 16.2-19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all Ps < 0.05). In multivariate analyses, there was a negative association between prior 177Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment. Conclusion: In this study, a PSA decline of greater than or equal to 50% after treatment with 225Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and PFS. Furthermore, previous 177Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses.
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Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias da Próstata/radioterapia , Actínio , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Taxa de Filtração Glomerular , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Intervalo Livre de Progressão , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/mortalidade , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/mortalidade , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron emission tomography in prostate carcinomas, are currently being explored for their staging and restaging potential as an alternative imaging modality in other solid tumor types where 18-F-fluorodeoxyglucose (FDG)-PET imaging has low diagnostic accuracy. In this paper, the currently available literature in this field is reviewed. Preliminary, mainly retrospective studies are encouraging, with evidence of improved diagnostic sensitivity and specificity in clear cell renal carcinoma, glioma, and hepatocellular carcinoma, leading to a change in patient management in several patients. However, the results published thus far warrant confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes.
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Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Tomografia por Emissão de Pósitrons , Animais , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons/métodos , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: The aim of this study was to compare liver and oncologic lesion standardized uptake values (SUV) obtained through two different reconstruction protocols, GE's newest clinical lesion detection protocol (Q.Clear) and the EANM Research Ltd (EARL) harmonization protocol, and to assess the clinical relevance of potential differences and possible implications for daily clinical practice using the PERCIST lesional inclusion criteria. NEMA phantom recovery coefficients (RC) and SUV normalized for lean body mass (LBM), referred to as SUV normalized for LBM (SUL), of liver and lesion volumes of interest were compared between the two reconstruction protocols. Head-to-toe PET/CT examinations and raw data from 64 patients were retrospectively retrieved. PET image reconstruction was carried out twice: once optimized for quantification, complying with EARL accreditation requirements, and once optimized for lesion detection, according to GE's Q.Clear reconstruction settings. RESULTS: The two reconstruction protocols showed different NEMA phantom RC values for different sphere sizes. Q.Clear values were always highest and exceeded the EARL accreditation maximum for smaller spheres. Comparison of liver SULmean showed a statistically significant but clinically irrelevant difference between both protocols. Comparison of lesion SULpeak and SULmax showed a statistically significant, and clinically relevant, difference of 1.64 and 4.57, respectively. CONCLUSIONS: For treatment response assessment using PERCIST criteria, the harmonization reconstruction protocol should be used as the lesion detection reconstruction protocol using resolution recovery systematically overestimates true SUL values.
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AIM: To investigate the prognostic value of F-18 FDG PET metabolic parameters in patients with anal carcinoma with and without human immunodeficiency virus infection (HIV). METHODS: Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained on F-18 FDG PET/CT images of treatment-naïve patients with locally advanced anal squamous cell carcinoma (ASSC). We compared patients' characteristics and F-18 FDG PET metabolic metrics between the HIV-infected patients and the HIV-uninfected patients. We did a simple Cox regression analysis followed by a multiple Cox regression analysis to determine factors predictive of death. RESULTS: We studied 33 patients including 21 HIV-infected individuals, mean age = 46.06 ± 12.59, female = 16, males = 17. Median CD4 count among HIV-infected patients was 400.50 cells/mm3 (IQR: 304.0 - 642.25). HIV-infected patients were younger than the HIV-uninfected patients at the time of diagnosis; 38.71 ± 7.98 vs. 58.92 ± 7.88 respectively, p < 0.001. No significant difference in the TNM stage and F-18 FDG metabolic parameters between the two groups. In a simple Cox regression analysis, MTV and TLG were significant predictors of death. Following a multiple Cox regression analysis, MTV and SUVmean were significant predictors of death. The median overall survival was 44.63 (95 % CI: 34.12 - 55.14) among HIV-infected patients versus 54.65 (95 % CI: 45.73 - 63.57) among HIV-uninfected patients, p = 0.415. CONCLUSION: HIV-infected patients are diagnosed with ASSC at a younger age compared with HIV-uninfected patients. F-18 FDG PET metabolic metrics especially MTV predicts overall survival in patients with ASCC. There is no difference in the overall survival of HIV-infected and HIV-uninfected patients treated similarly for ASSC. ZIEL:: Die Untersuchung der prognostischen Bedeutung der F-18 FDG PET metabolischen Aktivität bei HIV-negativen und positiven Analkarzinom-Patienten. METHODEN: Bestimmt wurden maximale standardisierten Uptake-Werte (SUVmax), mittlere standardisierte Uptake-Werte (SUVmean), das metabolische Tumorvolumen (MTV) sowie die gesamte Tumorlyse-Glukose (TLG) mittels F-18 FDG PET/CT bei behandlungsnaiven Patienten mit lokal fortgeschrittenem Anal-Plattenepithelkarzinom (ASSC). Die Patientencharakteristika und F-18 FDG PET metabolischen Ergebnisse der HIV-positiven und HIV-negativen Patienten wurden verglichen. Eine einfache Cox-Regressionsanalyse gefolgt von einer multiplen Cox-Regressionsanalyse diente der Bestimmung von Faktoren für Tod. ERGEBNISSE: Wir untersuchten 33 Patienten, davon 21 HIV-Infizierte, mittleres Alter = 46,06 ± 12,59, Frauen = 16, Männer = 17. Die mediane CD4-Zahl unter den HIV-Patienten war 400,50 Zellen/mm3 (IRQ: 304,0 - 642,25). Die HIV-infizierten Patienten waren jünger als die HIV-negativen Patienten zum Zeitpunkt der Diagnose; 38,71 ± 7,98 vs. 58,92 ± 7,88, p < 0,001. Es gab keinen signifikanten Unterschied in der TNM-Klassifikation und in den F-18 FDG metabolischen Werten zwischen den beiden Gruppen. In einer einfachen Cox-Regressionsanalyse waren MTV und TLG signifikante Prädiktoren für Tod. Das mediane Gersamtüberleben lag bei 44,63 (95 % CI: 34,12 - 55,14) unter den HIV-infizierten Patienten vs. 54,65 (95 % CI: 45,73 - 63,57) unter den HIV-negativen Patienten, p = 0,415. SCHLUSSFOLGERUNGEN: HIV-infizierte Patienten werden in jüngeren Jahren mit ASSC diagnostiziert im Vergleich zu HIV-negativen Patienten. F-18 FDG PET metabolische Aktivität, insbesondere MTV, kann das Gesamtüberleben von Patienten mit ASCC vorhersagen. Es gibt keinen Unterschied im Gesamtüberleben von HIV-infizierten und HIV-negativen Patienten bei gleicher Therapie des ASSC.
Assuntos
Neoplasias do Ânus/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Fluordesoxiglucose F18/administração & dosagem , Infecções por HIV/complicações , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Adulto , Fatores Etários , Idoso , Neoplasias do Ânus/complicações , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , HIV/fisiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Taxa de SobrevidaRESUMO
PURPOSE: 68Ga ligands targeting prostate-specific membrane antigen (PSMA) are rapidly emerging as a significant step forward in the management of prostate cancer. PSMA is a type II transmembrane protein with high expression in prostate carcinoma cells. We prospectively evaluated the use of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer and compared the results to those for technetium-99m (99mTc)-10-metacyloyloxydecyl dihydrogen phosphate (MDP) bone scintigraphy (BS). PATIENTS AND METHODS: A total 113 patients with biopsy-proven prostate cancer referred for standard-of-care BS were prospectively enrolled onto this study. 68Ga-PSMA PET/CT was performed after BS. Metastasis diagnosed on each technique was compared against a final diagnosis based on CT, magnetic resonance imaging, skeletal survey, clinical follow-up, and histologic correlation. RESULTS: Ninety-one bone lesions were interpreted as bone metastases in 25 men undergoing 68Ga-PSMA PET/CT compared to only 61 lesions in 19 men undergoing 99mTc-MDP BS. Of the 7 bone scans that missed skeletal metastases, 54% of these missed lesions were due to either marrow or lytic skeletal metastases. The median standardized uptake value in all malignant bone lesions was 13.84. 68Ga-PSMA PET/CT showed significantly higher sensitivity and accuracy than BS (96.2% vs. 73.1%, and 99.1% vs. 84.1%) for the detection of skeletal lesions. For extraskeletal lesions, 68Ga-PSMA PET/CT showed an additional 96 unexpected lesions with a median standardized uptake value of 17.6. CONCLUSION: 68Ga-PSMA PET/CT is superior to and can potentially replace bone scan in the evaluation for skeletal metastases in the clinical and trial setting because of its ability to detect lytic and bone marrow metastases.