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Over the last decades, technological developments in the field of radiology have resulted in a widespread use of imaging for personalising medicine in oncology, including patients with a sarcoma. New scanner hardware, imaging protocols, image reconstruction algorithms, radiotracers, and contrast media, enabled the assessment of the physical and biological properties of tumours associated with response to treatment. In this context, medical imaging has the potential to select sarcoma patients who do not benefit from (neo-)adjuvant treatment and facilitate treatment adaptation. Due to the biological heterogeneity in sarcomas, the challenge at hand is to acquire a practicable set of imaging features for specific sarcoma subtypes, allowing response assessment. This review provides a comprehensive overview of available clinical data on imaging-based response monitoring in sarcoma patients and future research directions. Eventually, it is expected that imaging-based response monitoring will help to achieve successful modification of (neo)adjuvant treatments and improve clinical care for these patients.
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Imagen Multimodal , Planificación de Atención al Paciente , Medicina de Precisión , Sarcoma/diagnóstico por imagen , Sarcoma/terapia , Biomarcadores , Proliferación Celular , Fibroblastos/patología , Glucosa/metabolismo , Humanos , Hipoxia/patología , Terapia Neoadyuvante , Metástasis de la Neoplasia , Sarcoma/irrigación sanguínea , Sarcoma/patologíaRESUMEN
BACKGROUND: It has been suggested that bone marrow cell injection may have beneficial effects in patients with chronic ischaemic heart disease. However, previous trials have led to discrepant results of cell-based therapy in patients with chronic heart failure. The aim of this study was to evaluate the efficacy of intramyocardial injection of mononuclear bone marrow cells in patients with chronic ischaemic heart failure with limited stress-inducible myocardial ischaemia. METHODS AND RESULTS: This multicentre, randomised, placebo-controlled trial included 39 patients with no-option chronic ischaemic heart failure with a follow-up of 12 months. A total of 19 patients were randomised to autologous intramyocardial bone marrow cell injection (cell group) and 20 patients received a placebo injection (placebo group). The primary endpoint was the group difference in change of left ventricular ejection fraction, as determined by single-photon emission tomography. On follow-up at 3 and 12 months, change of left ventricular ejection fraction in the cell group was comparable with change in the placebo group (Pâ¯= 0.47 and Pâ¯= 0.08, respectively). Also secondary endpoints, including left ventricle volumes, myocardial perfusion, functional and clinical parameters did not significantly change in the cell group as compared to placebo. Neither improvement was demonstrated in a subgroup of patients with stress-inducible ischaemia (Pâ¯= 0.54 at 3month and Pâ¯= 0.15 at 12-month follow-up). CONCLUSION: Intramyocardial bone marrow cell injection does not improve cardiac function, nor functional and clinical parameters in patients with severe chronic ischaemic heart failure with limited stress-inducible ischaemia. CLINICAL TRIAL REGISTRATION: NTR2516.
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BACKGROUND: Surgery is the cornerstone of treatment for many solid tumours. A wide variety of imaging modalities are available before surgery for staging, although surgeons still rely primarily on visual and haptic cues in the operating environment. Image and molecular guidance might improve the adequacy of resection through enhanced tumour definition and detection of aberrant deposits. Intraoperative modalities available for image- and molecular-guided cancer surgery are reviewed here. METHODS: Intraoperative cancer detection techniques were identified through a systematic literature search, with selection of peer-reviewed publications from January 2012 to January 2017. Modalities were reviewed, described and compared according to 25 predefined characteristics. To summarize the data in a comparable way, a three-point rating scale was applied to quantitative characteristics. RESULTS: The search identified ten image- and molecular-guided surgery techniques, which can be divided into four groups: conventional, optical, nuclear and endogenous reflectance modalities. Conventional techniques are the most well known imaging modalities, but unfortunately have the drawback of a defined resolution and long acquisition time. Optical imaging is a real-time modality; however, the penetration depth is limited. Nuclear modalities have excellent penetration depth, but their intraoperative use is limited by the use of radioactivity. Endogenous reflectance modalities provide high resolution, although with a narrow field of view. CONCLUSION: Each modality has its strengths and weaknesses; no single technique will be suitable for all surgical procedures. Strict selection of modalities per cancer type and surgical requirements is required as well as combining techniques to find the optimal balance.
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Neoplasias/cirugía , Radiografía Intervencional/métodos , Cirugía Asistida por Computador/métodos , Oncología Quirúrgica/métodos , Humanos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Trastuzumab is successfully used for the treatment of HER2-positive breast cancer. Because of its association with cardiotoxicity, LVEF is monitored by MUGA, though this is a relatively late measure of cardiac function. Diastolic dysfunction (DD) is believed to be an early predictor of cardiac impairment. We evaluate the merit of MUGA-derived diastolic function parameters in the early detection of trastuzumab-induced cardiotoxicity (TIC). METHODS AND RESULTS: 77 trastuzumab-treated patients with normal baseline systolic and diastolic function were retrospectively selected (n = 77). All serial MUGA examinations were re-analyzed for systolic and diastolic function parameters. 36 patients (47%) developed SD and 45 patients (58%) DD during treatment. Both systolic and diastolic parameters significantly decreased. Of the patients with SD, 24 (67%) also developed DD. DD developed prior to systolic impairment in 54% of cases, in 42% vice versa, while time to occurrence did not differ significantly (P = .52). This also applied to the subgroup of advanced stage breast cancer patients (P = .1). CONCLUSIONS: Trastzumab-induced SD and DD can be detected by MUGA. An impairment of MUGA-derived diastolic parameters does not occur prior to SD and therefore cannot be used as earlier predictors of TIC.
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Neoplasias de la Mama/tratamiento farmacológico , Angiografía Coronaria/métodos , Angiografía por Radionúclidos/métodos , Volumen Sistólico/efectos de los fármacos , Trastuzumab/efectos adversos , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/diagnóstico por imagen , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de la Mama/complicaciones , Cardiotoxinas/efectos adversos , Cardiotoxinas/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Trastuzumab/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: Assessing a diverse biomarker panel (NT-proBNP, TNF-α, galectin-3, IL-6, Troponin I, ST2 and sFlt-1) to detect subclinical cardiotoxicity after treatment with anthracyclines. METHODS: Of 55 breast cancer patients biomarkers were assessed and echocardiography was performed one year after treatment with anthracyclines. RESULTS: 29.1% of patients showed abnormal biomarker levels: NT-proBNP in 18.2%, TNF-α and Galectin-3 in 7.3%. IL-6, troponin I, ST2 and sFlt-1 were normal in all patients. A correlation between left ventricular ejection fraction (LVEF) and NT-proBNP was observed (r = -0.564, p ≤ 0.01). CONCLUSION: The evaluated biomarkers do not contribute to early detection. Future research should focus on NT-proBNP.
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Antineoplásicos/efectos adversos , Biomarcadores/sangre , Cardiotoxicidad/sangre , Galectina 3/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Factor de Necrosis Tumoral alfa/sangre , Adolescente , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad/diagnóstico , Cardiotoxicidad/etiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/diagnóstico , Ciclofosfamida/efectos adversos , Docetaxel , Doxorrubicina/efectos adversos , Ecocardiografía , Electroencefalografía , Ensayo de Inmunoadsorción Enzimática , Femenino , Corazón/efectos de los fármacos , Corazón/fisiopatología , Humanos , Persona de Mediana Edad , Sensibilidad y Especificidad , Taxoides/efectos adversos , Adulto JovenRESUMEN
Clinical studies have shown that bevacizumab beyond progression to first line therapy is beneficial for overall survival in advanced stage colorectal cancer. We studied the utility of several functional imaging modalities to assess the efficacy of bevacizumab beyond progression (BBP). All BALB/c mice with s.c. LS174T xenografts were treated with capecitabine, oxaliplatin and bevacizumab combination therapy. Tumor volume was assessed using caliper measurements. Increase of 1.5 times the initial volume on two subsequent measurements, was considered progression. In half of the mice bevacizumab treatment was continued (n = 13) after progressive disease was established, while the others received saline injections (n = 12). Within 3 days after progression, multi-modal imaging was performed using FDG-PET, diffusion weighted imaging, T2* and dynamic contrast enhanced MRI. Measurements were repeated 7 and 10 days after the first measurements. Afterwards, tumors were analyzed for expression of carbonic anhydrase IX, glucose transporter 1, 9 F1 to stain the vasculature and Ki67 to assess proliferation. In the BBP group tumor growth after progression was reduced compared to the control group (p < 0.01). FDG-PET showed a trend towards lower FDG uptake in the BBP group (p = 0.08). DWI, T2* and DCE-MRI parameters were not significantly different between both groups. The immunohistochemical analyses showed higher CAIX-positive fraction (p < 0.01) and lower Ki67 expression (p = 0.06) in the BBP group. The relative vascular area was significantly lower in the BBP group (p = 0.03). GLUT-1 expression and vascular density did not significantly differ between both groups. Bevacizumab after progression resulted in significant changes in the tumor proliferation and microenvironment compared to discontinuation of bevacizumab. FDG-PET may be sensitive to BBP-induced effects.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Progresión de la Enfermedad , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Bevacizumab , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Antígeno Ki-67/metabolismo , Ratones , Ratones Endogámicos BALB C , Carga Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. METHODS: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. RESULTS: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of -48% and -90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was -79% and -94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. CONCLUSIONS: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.
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PURPOSE: To investigate the performance of two microwave ablation (MWA) systems regarding ablation volume, ablation shape and variability. MATERIALS AND METHODS: In this ex vivo study, the Emprint and Amica MWA systems were used to ablate porcine livers at 4 different settings of time and power (3 and 5 minutes at 60 and 80 Watt). In total, 48 ablations were analysed for ablation size and shape using Vitrea Advanced Visualization software after acquisition of a 7T MRI scan. RESULTS: Emprint ablations were smaller (11,1 vs. 21,1 mL p < 0.001), more spherical (sphericity index of 0.89 vs. 0.59 p < 0.001) and showed less variability than Amica ablations. In both systems, longer ablation time and higher power resulted in significantly larger ablation volumes. CONCLUSION: Emprint ablations were more spherical, and the results showed a lower variability than those of Amica ablations. This comes at the price of smaller ablation volumes.
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Técnicas de Ablación/métodos , Hígado/cirugía , Animales , Ablación por Catéter/métodos , Microondas , Modelos Animales , Reproducibilidad de los Resultados , PorcinosRESUMEN
BACKGROUND: The combination treatment regimen of thermal ablation (TA) and transarterial chemoembolization (TACE) has gained a place in treatment of hepatocellular carcinoma (HCC) lesions > 3 cm unsuitable for surgery. Despite a high heterogeneity in the currently used treatment protocols, the pooled results of combined treatments seem to outperform those of TA or TACE alone. TACE preceding TA has been studied extensively, while results of the reverse treatment sequence are lacking. In this retrospective cohort study we compared the two treatment sequences. PATIENTS AND METHODS: 38 patients (median age: 68.5 yrs (range 40-84), male: 34, liver cirrhosis: 33, early stage HCC: 21, intermediate stage HCC: 17) were included in two tertiary referral centers, of whom 27 were treated with TA and adjuvant TACE (TA + TACE). The other 11 patients received TA with neoadjuvant TACE (TACE + TA). Overall survival (OS), time to progression (TTP) and local tumor progression (LTP) free survival were determined for the entire cohort and compared between the two treatment sequences. RESULTS: The median OS of all patients was 52.7 months and the median time to LTP was 11.5 months (censored for liver transplantation). No differences were found with respect to OS between the two treatment sequences. Median time to LTP for TACE + TA was 23.6 months and 8.1 months for TA + TACE (p = 0.19). DISCUSSION: No statistical differences were found for OS, TTP and time to LTP between patients treated with TA combined with neoadjuvant or adjuvant TACE.
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Carcinoma Hepatocelular , Ablación por Catéter , Quimioembolización Terapéutica , Neoplasias Hepáticas , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Terapia Combinada , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIM: In therapy response monitoring by [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (DMRglu). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size. METHODS: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROIfixed thresholds was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROIfixed volumes was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROIfixed volumes is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival. RESULTS: In CRC, only ROIfixed volumes based DMRglu showed significant predictive ability. In NSCLC, both techniques showed significant predictive ability. During multivariate analysis, ROIfixed volumes determined DMRglu was an independent predictor for both overall and progression free survival in NSCLC whereas ROIfixed thresholds determined MRglu was not. After dichotomization at the median DMRglu, median survival ratio was higher in ROIfixed volumes than ROIfixed thresholds for CRC (overall survival: 1.78 vs 1.25, progression free survival: 1.57 vs 1.21) and NSCLC (overall survival: 2.01 vs 2.01, progression free survival: 2.93 vs 2.13). CONCLUSION: ROIfixed volumes based DMRglu shows better correlation with survival than DMRglu determined from a ROIfixed thresholds.
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The urokinase plasminogen activator receptor (uPAR) plays a multifaceted role in almost any process where migration of cells and tissue-remodeling is involved such as inflammation, but also in diseases as arthritis and cancer. Normally, uPAR is absent in healthy tissues. By its carefully orchestrated interaction with the protease urokinase plasminogen activator and its inhibitor (plasminogen activator inhibitor-1), uPAR localizes a cascade of proteolytic activities, enabling (patho)physiologic cell migration. Moreover, via the interaction with a broad range of cell membrane proteins, like vitronectin and various integrins, uPAR plays a significant, but not yet completely understood, role in differentiation and proliferation of cells, affecting also disease progression. The implications of these processes, either for diagnostics or therapeutics, have received much attention in oncology, but only limited beyond. Nonetheless, the role of uPAR in different diseases provides ample opportunity to exploit new applications for targeting. Especially in the fields of oncology, cardiology, rheumatology, neurology, and infectious diseases, uPAR-targeted molecular imaging could offer insights for new directions in diagnosis, surveillance, or treatment options.
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PURPOSE: After radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), pre- and postinterventional contrast-enhanced CT (CECT) images are usually qualitatively interpreted to determine technical success, by eyeballing. The objective of this study was to evaluate the feasibility of quantitative assessment, using a nonrigid CT-CT coregistration algorithm. MATERIALS AND METHODS: 25 patients treated with RFA for HCC between 2009 and 2014 were retrospectively included. Semiautomated coregistration of pre- and posttreatment CECT was performed independently by two radiologists. In scans with a reliable registration, the tumor and ablation area were delineated to identify the side and size of narrowest RFA margin. In addition, qualitative assessment was performed independently by two other radiologists to determine technical success and the anatomical side and size of narrowest margin. Interobserver agreement rates were determined for both methods, and the outcomes were compared with occurrence of local tumor progression (LTP). RESULTS: CT-CT coregistration was technically feasible in 18/25 patients with almost perfect interobserver agreement for quantitative analysis (κ = 0.88). The interobserver agreement for qualitative RFA margin analysis was κ = 0.64. Using quantitative assessment, negative ablative margins were found in 12/18 patients, with LTP occurring in 8 of these patients. In the remaining 6 patients, quantitative analysis demonstrated complete tumor ablation and no LTP occurred. CONCLUSION: Feasibility of quantitative RFA margin assessment using nonrigid coregistration of pre- and postablation CT is limited, but appears to be a valuable tool in predicting LTP in HCC patients (p=0.013).
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BACKGROUND: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer. METHODS: Dynamic FDG-PET was carried out before and at 2 (n = 50) and 6 months (n = 19) after the start of treatment. Quantitative Patlak analysis [metabolic rate of glucose (MRGlu)] and a simplified method to measure glucose metabolism [standardized uptake value (SUV)] were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates. RESULTS: There was an increase in the rates of death (P = 0.049 for DeltaMRGlu PET1-2; P = 0.017 for DeltaSUV PET1-2; P = 0.032 for DeltaMRGlu PET1-3; P = 0.048 for DeltaSUV PET1-3) and progression (P = 0.026 for DeltaMRGlu PET1-2; P = 0.035 for DeltaSUV PET1-2; P = 0.041 for DeltaMRGlu PET1-3; P = 0.081 for DeltaSUV PET1-3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of DeltaMRGlu and DeltaSUV cut-off levels. CONCLUSION: The degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG-PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable.
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Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/mortalidad , Fluorodesoxiglucosa F18 , Invasividad Neoplásica/patología , Tomografía de Emisión de Positrones , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Terapia Combinada , Supervivencia sin Enfermedad , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
CONTEXT: Patients with thyroid nodules of indeterminate cytology undergo diagnostic surgery according to current guidelines. In 75% of patients, the nodule is benign. In these patients, surgery was unnecessary and unbeneficial because complications may occur. Preoperative fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) was found to have a very high negative predictive value (96%) and might therefore avoid futile surgery, complications, and costs. In the United States, two molecular tests of cytology material are routinely used for this purpose. OBJECTIVE: Five-year cost-effectiveness for routine implementation of FDG-PET/CT was evaluated in adult patients with indeterminate fine-needle aspiration cytology and compared with surgery in all patients and both molecular tests. DESIGN: A Markov decision model was developed to synthesize the evidence on cost-effectiveness about the four alternative strategies. The model was probabilistically analyzed. One-way sensitivity analyses of deterministic input variables likely to influence outcome were performed. SETTING AND SUBJECTS: The model was representative for adult patients with cytologically indeterminate thyroid nodules. MAIN OUTCOME MEASURES: The discounted incremental net monetary benefit (iNMB), the efficiency decision rule containing outcomes as quality-adjusted life-years and (direct) medical cost, of implementation of FDG-PET/CT is displayed. RESULTS: Full implementation of FDG-PET/CT resulted in 40% surgery for benign nodules, compared with 75% in the conventional approach, without a difference in recurrence free and overall survival. The FDG-PET/CT modality is the more efficient technology, with a mean iNMB of 3684 compared with surgery in all. Also, compared with a gene expression classifier test and a molecular marker panel, the mean iNMB of FDG-PET/CT was 1030 and 3851, respectively, and consequently the more efficient alternative. CONCLUSION: Full implementation of preoperative FDG-PET/CT in patients with indeterminate thyroid nodules could prevent up to 47% of current unnecessary surgery leading to lower costs and a modest increase of health-related quality of life. Compared with an approach with diagnostic surgery in all patients and both molecular tests, it is the least expensive alternative with similar effectiveness as the gene-expression classifier.
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Técnicas de Apoyo para la Decisión , Imagen Multimodal/economía , Tomografía de Emisión de Positrones/economía , Nódulo Tiroideo , Tomografía Computarizada por Rayos X/economía , Adulto , Análisis Costo-Beneficio , Árboles de Decisión , Fluorodesoxiglucosa F18 , Costos de la Atención en Salud , Humanos , Cadenas de Markov , Modelos Econométricos , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Sensibilidad y Especificidad , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/economía , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/economía , Tomografía Computarizada por Rayos X/métodosRESUMEN
The purpose of this study was to assess the effect of bevacizumab on vasculature and hypoxia in a colorectal tumor model. Nude mice with subcutaneous LS174T tumors were treated with bevacizumab or saline. To assess tumor properties, separate groups of mice were imaged using (18) F-Fluoromisonidazole (FMISO) and (18) F-Fluorodeoxyglucose (FDG) positron emission tomography or magnetic resonance imaging before and 2, 6 and 10 days after the start of treatment. Tumors were harvested after imaging to determine hypoxia and vascular density immunohistochemically. The T2 * time increased significantly less in the bevacizumab group. FMISO uptake increased more over time in the control group. Vessel density significantly decreased in the bevacizumab-treated group. The Carbonic anhydrase 9 (CAIX) and glucose uptake transporter 1 (GLUT1) fractions were higher in bevacizumab-treated tumors. However, the hypoxic fraction showed no significant difference. Bevacizumab led to shorter T2 * times and higher GLUT1 and CAIX expression, suggesting an increase in hypoxia and a higher glycolytic rate. This could be a mechanism of resistance to bevacizumab. The increase in hypoxia, however, could not be demonstrated by pimonidazole/FMISO, possibly because distribution of these tracers is hampered by bevacizumab-induced effects on vascular permeability and perfusion.
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Inhibidores de la Angiogénesis/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/patología , Hipoxia/diagnóstico , Neovascularización Patológica/diagnóstico , Fármacos Sensibilizantes a Radiaciones , Inhibidores de la Angiogénesis/sangre , Animales , Anticuerpos Monoclonales Humanizados/sangre , Bevacizumab , Neoplasias Colorrectales/tratamiento farmacológico , Ensayo de Inmunoadsorción Enzimática , Femenino , Fluorodesoxiglucosa F18 , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Técnicas para Inmunoenzimas , Imagen por Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Misonidazol/análogos & derivados , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Nitroimidazoles , Tomografía de Emisión de Positrones , RadiofármacosRESUMEN
AIM: Cardiac 123I metaiodobenzylguanidine (MIBG) imaging can be influenced by several factors. We evaluated the relationship between catecholamine measurements and cardiac 123I MIBG uptake in neuroblastoma patients. PATIENTS, METHODS: 30 neuroblastoma patients were retrospectively assessed on cardiac 123I MIBG uptake and urinary catecholamine dopamine and metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA). Cardiac 123I MIBG uptake was quantified by heart-to-mediastinum (H/M) ratios, which were calculated into standard deviation scores (SDS) using age-specific reference values. RESULTS: In 17 (57%) and 12 patients (40%) H/M ratio measurements were below -1.0 and -2.0 SDS at diagnosis. A significant inverse correlation between the average of urine metabolites HVA and VMA, and H/M ratio SDS was observed (r -.39, p = 0.04). Furthermore, there was a significant correlation between the urinary catecholamine metabolite HVA and H/M ratio SDS (r -.40, p=0.04). CONCLUSION: Routine calculation of H/M ratios in 123I MIBG scintigrams of neuroblastoma patients is not helpful because it will not identify cardiac ventricular dysfunction in this patient category. A low H/M ratio on 123I MIBG scintigraphy is explained by increased cathecholamine levels secreted by neuroblastoma tumours.
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3-Yodobencilguanidina/farmacocinética , Catecolaminas/metabolismo , Corazón/diagnóstico por imagen , Miocardio/metabolismo , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/metabolismo , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Cintigrafía , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a known method to diagnose inflammatory processes and thus may be a promising imaging technique to detect anastomotic bowel leak. The aim of this study was to assess postoperative FDG uptake in colorectal anastomosis in patients without suspicion of active infection or anastomotic leakage. PATIENTS, METHODS: Design of a prospective observational pilot study in order to assess normal FDG uptake in the patient anastomosis after colorectal surgery. Patients that underwent colorectal surgery with primary anastomosis received FDG-PET of the abdomen, 2-6 days postoperatively. RESULTS: 35 patients met the inclusion criteria. Three patients were not scanned for various reasons. Of the remaining 32 patients, one demonstrated an increased uptake of FDG at the site of the anastomosis. In the other 31 patients FDG uptake was negligible (n = 17) or scored as physiological (n = 14). None of the scanned patients developed a clinical relevant anastomotic leakage within the first 30 days after surgery. CONCLUSION: The present study shows that FDG uptake in colorectal anastomosis remains low within the first six days after surgery in patients without anastomotic leakage. Therefore, FDG-PET might be useful to investigate further as a tool to detect anastomotic leakage in an the early postoperative phase.
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Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Cirugía Colorrectal/efectos adversos , Fluorodesoxiglucosa F18 , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
AIM: In therapy response monitoring by [¹8F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (ΔMR(glu)). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size. METHODS: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROI(fixed thresholds) was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROI(fixed volumes) was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROI(fixed volumes) is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival. RESULTS: In CRC, only ROI(fixed volumes) based ΔMR(glu) showed significant predictive ability. In NSCLC, both techniques showed significant predictive ability. During multivariate analysis, ROI(fixed volumes) determined ΔMR(glu) was an independent predictor for both overall and progression free survival in NSCLC whereas ROI(fixed thresholds) determined MRglu was not. After dichotomization at the median ΔMR(glu), median survival ratio was higher in ROI(fixed volumes) than ROI(fixed thresholds) for CRC (overall survival: 1.78 vs 1.25, progression free survival: 1.57 vs 1.21) and NSCLC (overall survival: 2.01 vs 2.01, progression free survival: 2.93 vs 2.13). CONCLUSION: ROI(fixed volumes) based ΔMR(glu) shows better correlation with survival than ΔMR(glu) determined from a ROI(fixed thresholds).
Asunto(s)
Fluorodesoxiglucosa F18/metabolismo , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias/metabolismo , Neoplasias/mortalidad , Tomografía de Emisión de Positrones/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Radiofármacos/metabolismo , Adulto , Anciano , Antineoplásicos/uso terapéutico , Simulación por Computador , Femenino , Humanos , Persona de Mediana Edad , Modelos Biológicos , Neoplasias/tratamiento farmacológico , Países Bajos/epidemiología , Prevalencia , Pronóstico , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Positron emission tomography (PET) using [(18)F]-fluoro-2'-deoxy-D-glucose (FDG) has an added value in the clinical management of patients with colorectal carcinoma (CRC). This includes restaging patients before surgical resection or local recurrence of liver metastases, assessment whether residual lesions are scar or recurrence and in pinpointing recurrence in case of unexplained increase in serum levels of carcinoembryonic antigen. At present, there is an increasing interest in new roles for FDG-PET, especially for characterization of lesions, for prognosis and response prediction and for early evaluation of treatment response to commenced therapy. FDG-PET may lead to better selection of patients for different therapeutic options or to early individual adjustment of current treatment. This systematic review aims to provide an up-to-date overview of literature on the current and potential value of FDG-PET in CRC patients by addressing staging and recurrence detection, prognosis and response prediction and evaluation of preoperative (chemo)radiotherapy for primary rectal carcinoma, ablative treatment for unresectable liver metastases and chemotherapy for advanced CRC.