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1.
Ultraschall Med ; 45(1): 36-46, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37748503

RESUMO

Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.


Assuntos
Meios de Contraste , Neoplasias , Humanos , Ultrassonografia/métodos , Perfusão
2.
J Magn Reson Imaging ; 58(1): 122-132, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36269053

RESUMO

BACKGROUND: Head and neck cancer (HNC) is the sixth most prevalent cancer worldwide. Dynamic contrast-enhanced MRI (DCE-MRI) helps in diagnosis and prognosis. Quantitative DCE-MRI requires an arterial input function (AIF), which affects the values of pharmacokinetic parameters (PKP). PURPOSE: To evaluate influence of four individual AIF measurement methods on quantitative DCE-MRI parameters values (Ktrans , ve , kep , and vp ), for HNC and muscle. STUDY TYPE: Prospective. POPULATION: A total of 34 HNC patients (23 males, 11 females, age range 24-91) FIELD STRENGTH/SEQUENCE: A 3 T; 3D SPGR gradient echo sequence with partial saturation of inflowing spins. ASSESSMENT: Four AIF methods were applied: automatic AIF (AIFa) with up to 50 voxels selected from the whole FOV, manual AIF (AIFm) with four voxels selected from the internal carotid artery, both conditions without (Mc-) or with (Mc+) motion correction. Comparison endpoints were peak AIF values, PKP values in tumor and muscle, and tumor/muscle PKP ratios. STATISTICAL TESTS: Nonparametric Friedman test for multiple comparisons. Nonparametric Wilcoxon test, without and with Benjamini Hochberg correction, for pairwise comparison of AIF peak values and PKP values for tumor, muscle and tumor/muscle ratio, P value ≤ 0.05 was considered statistically significant. RESULTS: Peak AIF values differed significantly for all AIF methods, with mean AIFmMc+ peaks being up to 66.4% higher than those for AIFaMc+. Almost all PKP values were significantly higher for AIFa in both, tumor and muscle, up to 76% for mean Ktrans values. Motion correction effect was smaller. Considering tumor/muscle parameter ratios, most differences were not significant (0.068 ≤ Wilcoxon P value ≤ 0.8). DATA CONCLUSION: We observed important differences in PKP values when using either AIFa or AIFm, consequently choice of a standardized AIF method is mandatory for DCE-MRI on HNC. From the study findings, AIFm and inflow compensation are recommended. The use of the tumor/muscle PKP ratio should be of interest for multicenter studies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.


Assuntos
Meios de Contraste , Neoplasias de Cabeça e Pescoço , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/farmacocinética , Estudos Prospectivos , Aumento da Imagem/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Algoritmos , Reprodutibilidade dos Testes
3.
Int J Mol Sci ; 24(22)2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-38003400

RESUMO

Standard imaging cannot reliably predict the nature of renal tumors. Among malignant renal tumors, clear cell renal cell carcinoma (ccRCC) is the most common histological subtype, in which the vascular endothelial growth factor 2 (VEGFR-2) is highly expressed in the vascular endothelium. BR55, a contrast agent for ultrasound imaging, consists of gas-core lipid microbubbles that specifically target and bind to the extracellular portion of the VEGFR-2. The specific information provided by ultrasound molecular imaging (USMI) using BR55 was compared with the vascular tumor expression of the VEGFR-2 by immunohistochemical (IHC) staining in a preclinical model of ccRCC. Patients' ccRCCs were orthotopically grafted onto Nod-Scid-Gamma (NSG) mice to generate patient-derived xenografts (PdX). Mice were divided into four groups to receive either vehicle or axitinib an amount of 2, 7.5 or 15 mg/kg twice daily. Perfusion parameters and the BR55 ultrasound contrast signal on PdX renal tumors were analyzed at D0, D1, D3, D7 and D11, and compared with IHC staining for the VEGFR-2 and CD34. Significant Pearson correlation coefficients were observed between the area under the curve (AUC) and the CD34 (0.84, p < 10-4), and between the VEGFR-2-specific signal obtained by USMI and IHC (0.72, p < 10-4). USMI with BR55 could provide instant, quantitative information on tumor VEGFR-2 expression to characterize renal masses non-invasively.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Camundongos , Animais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular , Xenoenxertos , Ultrassonografia/métodos , Imagem Molecular/métodos , Meios de Contraste , Neoplasias Renais/diagnóstico por imagem
4.
Eur Radiol ; 32(12): 8617-8628, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35678860

RESUMO

OBJECTIVES: In the Cancer Core Europe Consortium (CCE), standardized biomarkers are required for therapy monitoring oncologic multicenter clinical trials. Multiparametric functional MRI and particularly diffusion-weighted MRI offer evident advantages for noninvasive characterization of tumor viability compared to CT and RECIST. A quantification of the inter- and intraindividual variation occurring in this setting using different hardware is missing. In this study, the MRI protocol including DWI was standardized and the residual variability of measurement parameters quantified. METHODS: Phantom and volunteer measurements (single-shot T2w and DW-EPI) were performed at the seven CCE sites using the MR hardware produced by three different vendors. Repeated measurements were performed at the sites and across the sites including a traveling volunteer, comparing qualitative and quantitative ROI-based results including an explorative radiomics analysis. RESULTS: For DWI/ADC phantom measurements using a central post-processing algorithm, the maximum deviation could be decreased to 2%. However, there is no significant difference compared to a decentralized ADC value calculation at the respective MRI devices. In volunteers, the measurement variation in 2 repeated scans did not exceed 11% for ADC and is below 20% for single-shot T2w in systematic liver ROIs. The measurement variation between sites amounted to 20% for ADC and < 25% for single-shot T2w. Explorative radiomics classification experiments yield better results for ADC than for single-shot T2w. CONCLUSION: Harmonization of MR acquisition and post-processing parameters results in acceptable standard deviations for MR/DW imaging. MRI could be the tool in oncologic multicenter trials to overcome the limitations of RECIST-based response evaluation. KEY POINTS: • Harmonizing acquisition parameters and post-processing homogenization, standardized protocols result in acceptable standard deviations for multicenter MR-DWI studies. • Total measurement variation does not to exceed 11% for ADC in repeated measurements in repeated MR acquisitions, and below 20% for an identical volunteer travelling between sites. • Radiomic classification experiments were able to identify stable features allowing for reliable discrimination of different physiological tissue samples, even when using heterogeneous imaging data.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Neoplasias/diagnóstico por imagem , Europa (Continente) , Reprodutibilidade dos Testes
5.
World J Urol ; 39(8): 2831-2841, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33616708

RESUMO

PURPOSE: Renal cell carcinoma (RCC) incidence has considerably increased during the last decades without any real impact on age-standardized mortality. It questions the relevance of aggressive treatments carrying potential side effects. Conservative management should be considered for frail patients. Comorbidity and frailty assessment in RCC patients is paramount before engaging a treatment. METHODS: Narrative, non-systematic review based on PubMed and EMBASE search with the terms "renal neoplasm", "elderly, frail", "comorbidities", "active surveillance", "metastatic". The selection was restricted to articles written in English. RESULTS: Comorbidity and frailty assessment go along with the cancer-specific aggressivity and intervention risks assessment. In localized disease, several standardized algorithms offer patient health evaluation to define how suitable the patient would be for curative treatment. The pre-operative American Society of Anesthesiologists and the age-adjusted Charlson's scores are the most widely used. At the metastatic stage, drug combinations based on immunotherapies and targeted therapies improved cancer outcomes at the price of significant toxicities. Frail patients are not always suitable for such strategies. Commonly used scores like the International Metastatic RCC Database Consortium or Memorial Sloan Kettering Cancer Center integrate features to define patients' risk groups, more specifically the Karnofsky Performance Score is an easy way to document the frailty. CONCLUSIONS: Comorbidity and frailty have to be assessed at any stage of the RCC disease based on a standardized scoring system to define the most suitable treatment strategy ranging from surveillance to aggressive treatment.


Assuntos
Carcinoma de Células Renais , Fragilidade , Avaliação Geriátrica/métodos , Neoplasias Renais , Risco Ajustado/métodos , Idoso , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Comorbidade , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Seleção de Pacientes , Conduta Expectante
6.
Eur Radiol ; 31(8): 6001-6012, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33492473

RESUMO

Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. KEY POINTS: • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.


Assuntos
Radiologia , Tomografia Computadorizada por Raios X , Biomarcadores , Consenso , Humanos , Processamento de Imagem Assistida por Computador
7.
MAGMA ; 34(6): 845-857, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34091826

RESUMO

OBJECT: To develop new imaging biomarkers of therapeutic efficacy through the quantification of intratumoral microvascular heterogeneity. MATERIALS AND METHODS: The described method was a combination of non-supervised clustering and extraction of intratumoral complexity features (ICF): number of non-connected objects, volume fraction. It was applied to a set of 3D DCE-MRI Ktrans maps acquired previously on tumor bearing mice prior to and on day 4 of anti-angiogenic treatment. Evolutions of ICF were compared to conventional summary statistics (CSS) and to heterogeneity related whole tumor texture features (TF) on treated (n = 9) and control (n = 6) mice. RESULTS: Computed optimal number of clusters per tumor was 4. Several intratumoral features extracted from the clusters were able to monitor a therapy effect. Whereas no feature significantly changed for the control group, 6 features significantly changed for the treated group (4 ICF, 2 CSS). Among these, 5 also significantly differentiated the two groups (3 ICF, 2 CSS). TF failed in demonstrating differences within and between the two groups. DISCUSSION: ICF are potential imaging biomarkers for anti-angiogenic therapy assessment. The presented method may be expected to have advantages with respect to texture analysis-based methods regarding interpretability of results and setup of standardized image analysis protocols.


Assuntos
Meios de Contraste , Neoplasias , Animais , Análise por Conglomerados , Estudos de Viabilidade , Imageamento por Ressonância Magnética , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
8.
Recent Results Cancer Res ; 216: 765-771, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32594405

RESUMO

Neovascularization is a key stage in the growth of malignancies beyond 2-3 mm3. This neoangiogenesis is an important target for novel anticancer treatments [1], and many new antiangiogenesis or antivascular treatments aim at destroying or limiting the growth of tumor vessels [2].


Assuntos
Neoplasias/irrigação sanguínea , Neoplasias/diagnóstico por imagem , Neovascularização Patológica/tratamento farmacológico , Ultrassonografia , Humanos , Neoplasias/tratamento farmacológico
9.
Eur Radiol ; 30(9): 5021-5028, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32323012

RESUMO

OBJECTIVES: The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients. METHODS: From January 2010 to May 2017, 550 patients with stage IV lung adenocarcinoma with molecular analysis were studied retrospectively including 135 EGFR-mutated, 81 ALK-rearrangement, 47 BRAF-mutated, 141 KRAS-mutated, and 146 negative tumors for these 4 mutations (4N). After review of the complete imaging report by two radiologists (junior and senior) to identify metastatic sites, univariate correlation analyzes were performed. RESULTS: We found differences in metastatic tropism depending on the molecular alteration type when compared with the non-mutated 4N group: in the EGFR group, pleural metastases were more frequent (32% versus 20%; p = 0.021), and adrenal and node metastases less common (6% versus 23%; p < 0.001 and 11% versus 23%; p = 0.011). In the ALK group, there were more brain and lung metastases (respectively 42% versus 29%; p = 0.043 and 37% versus 24%; p = 0.037). In the BRAF group, pleural and pericardial metastases were more common (respectively 47% versus 20%; p < 0.001 and 11% versus 3%; p = 0.04) and bone metastases were rarer (21% versus 42%; p = 0.011). Lymphangitis was more frequent in EGFR, ALK, and BRAF groups (respectively 6%, 7%, and 15% versus 1%); p = 0.016; p = 0.009; and p < 0.001. CONCLUSION: The application of these correlations between molecular status and metastatic tropism in clinical practice may lead to earlier and more accurate identification of patients for targeted therapy. KEY POINTS: • Bone and brain metastasis are the most common organs involved in lung adenocarcinoma but the relative incidence of each metastatic site depends on the molecular alteration. • EGFR-mutated tumors preferentially spread to the pleura and less commonly to adrenals, ALK-rearrangement tumors usually spread to the brain and the lungs, whereas BRAF-mutated tumors are unlikely to spread to bones and have a serous (pericardial ad pleural) tropism. • These correlations could help in the clinical management of patients with metastatic lung adenocarcinoma.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , DNA de Neoplasias/genética , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico , Mutação , Estadiamento de Neoplasias , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Ultraschall Med ; 41(5): 562-585, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32707595

RESUMO

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.


Assuntos
Meios de Contraste , Ultrassonografia , Meios de Contraste/normas , Humanos , Ultrassonografia/normas
11.
Int J Mol Sci ; 21(19)2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998233

RESUMO

Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known for interfering with hypoxia processes. Renal carcinoma encompasses a broad spectrum of histological entities and is also described as a heterogeneous malignant tumor. Recently, various combinations of checkpoint inhibitors and targeted therapies have been validated to manage this disease. Reliable markers to confirm the diagnosis, estimate the prognosis, predict or monitor the treatment response are required. Molecular imaging developments allow a comprehensive analysis of the tumor, overcoming the spatial heterogeneity issue. CAIX, being highly expressed at the tumor cell surfaces of clear cell renal carcinoma, also represents a potential treatment target. In this manuscript we reviewed the current knowledge from the literature on the pathophysiological interactions between renal cell carcinoma and CAIX, the role of CAIX as a marker for diagnosis, prognosis, treatment monitoring and molecular imaging, and the potential target for therapeutic strategies.


Assuntos
Antígenos de Neoplasias/genética , Anidrase Carbônica IX/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Hipóxia/genética , Neoplasias Renais/genética , Terapia de Alvo Molecular/métodos , Anticorpos Monoclonais/uso terapêutico , Antígenos de Neoplasias/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Anidrase Carbônica IX/antagonistas & inibidores , Anidrase Carbônica IX/metabolismo , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Gerenciamento Clínico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Hipóxia/diagnóstico por imagem , Hipóxia/tratamento farmacológico , Hipóxia/imunologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Imagem Molecular/métodos , Prognóstico , Proteínas Recombinantes de Fusão/uso terapêutico , Transdução de Sinais
14.
Ultrason Imaging ; 40(5): 325-338, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29923458

RESUMO

Tumor microvascularization is a biomarker of response to antiangiogenic treatments and is accurately assessed by ultrasound imaging. Imaging modes used to visualize slow flows include Power Doppler imaging, dynamic contrast-enhanced ultrasonography, and more recently, microvascular Doppler. Flow phantoms are used to evaluate the performance of Doppler imaging techniques, but they do not have a steady flow and sufficiently small channels. We report a novel device for robust and stable microflow measurements and the study of the microvascularization. Based on microfluidics technology, the prototype features wall-less cylindrical channels of diameters ranging from as small as 147 up to 436 µm, cast in a soft silicone polymer and perfused via a microfluidic flow pressure controller. The device was assessed using flow rates from 49 to 146 µL/min, with less than 1% coefficient of variation over three minutes, corresponding to velocities of 6 to 142 mm/s. This enabled us to evaluate and confirm the reliability of the Superb Microvascular Imaging Doppler mode compared with the Power Doppler mode at these flow rates in the presence of vibrations mimicking physiological motion.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Microvasos/diagnóstico por imagem , Imagens de Fantasmas , Ultrassonografia/métodos , Velocidade do Fluxo Sanguíneo , Reprodutibilidade dos Testes
15.
BMC Cancer ; 17(1): 326, 2017 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-28499444

RESUMO

BACKGROUND: Survival of childhood, adolescent and young adult (CAYA) cancers has increased with progress in the management of the treatments and has reached more than 80% at 5 years. Nevertheless, these survivors are at great risk of second cancers and non-malignant co-morbidities in later life. DeNaCaPST is a non-interventional study whose aim is to organize a national screening for thyroid cancer and breast cancer in survivors of CAYA cancers. It will study the compliance with international recommendations, with the aim, regarding a breast screening programme, of offering for every woman living in France, at equal risk, an equal screening. METHOD: DeNaCaPST trial is coordinated by the INSERM 1018 unit in cooperation with the LEA (French Childhood Cancer Survivor Study for Leukaemia) study's coordinators, the long term follow up committee and the paediatric radiation committee of the SFCE (French Society of Childhood Cancers). A total of 35 centres spread across metropolitan France and la Reunion will participate. FCCSS (French Childhood Cancer Survivor Study), LEA and central registry will be interrogated to identify eligible patients. To participate, centers agreed to perform a complete "long-term follow-up consultations" according to good clinical practice and the guidelines of the SFCE (French Society of Children Cancers). DISCUSSION: As survival has greatly improved in childhood cancers, detection of therapy-related malignancies has become a priority even if new radiation techniques will lead to better protection for organs at risk. International guidelines have been put in place because of the evidence for increased lifetime risk of breast and thyroid cancer. DeNaCaPST is based on these international recommendations but it is important to recognize that they are based on expert consensus opinion and are supported by neither nonrandomized observational studies nor prospective randomized trials in this specific population. Over-diagnosis is a phenomenon inherent in any screening program and therefore such programs must be evaluated.


Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Segunda Neoplasia Primária/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Mama/patologia , Feminino , França , Humanos , Glândula Tireoide/patologia
18.
Invest New Drugs ; 32(2): 312-22, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23979492

RESUMO

PURPOSE: Improved prognostic accuracy for treatment response and a wider understanding of drug effects in humans are crucial for enhancing the utility of sorafenib and other promising targeted therapies. We developed a strategy of global genomic investigation of sequential tumor biopsy samples at baseline and 21 days post treatment, and applied this approach in a phase I study of sorafenib plus dacarbazine in patients with solid tumors. The objective of this study was also to validate functional parameters of DCE-US as surrogate markers to predict earlier response. EXPERIMENTAL DESIGN: Patients received 21-day cycles of oral sorafenib, 400 mg twice daily and dacarbazine, 1,000 mg/m(2) in a 1-h intravenous infusion on day 1. Efficacy was assessed using response evaluation criteria in solid tumors. Sequential biopsy samples (baseline and day 21) were obtained from the same tumor. Changes from baseline in global gene expression (GE) measured by genomic microarrays and in tumor vascularity at baseline, D8, D21, D 42 and every 2 cycles using dynamic contrast-enhanced ultrasonography (DCE-US) were analyzed for patients with and without a clinical response to treatment at 3 months. RESULTS: Among 23 patients evaluable for treatment efficacy, 17 were eligible for gene expression and DCE-US analyses. One patient achieved a partial response; 14 exhibited stable disease. Ten patients were defined as exhibiting stable disease (SD) and 7, progressive disease (PD) at 3 months. Genomic analyses identified a 237-gene signature that distinguished SD from PD at 3 months. Of note, CDK4 overexpression and PDGFR downregulation were associated with PD. Functional parameters of DCE-US representing the blood volume at baseline, day 8, and day 21 were correlated with disease progression at 3 months. CONCLUSIONS: This novel approach of sequential investigations in a phase I trial was feasible, detecting early changes in gene expression and tumor vascularity evaluated using DCE-US that may be predictive of clinical outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Regulação Neoplásica da Expressão Gênica , Neoplasias/tratamento farmacológico , Idoso , Biópsia , Dacarbazina/administração & dosagem , Feminino , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/genética , Neoplasias/patologia , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Sorafenibe , Ultrassonografia
19.
Eur J Cancer ; 202: 114020, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38502988

RESUMO

BACKGROUND: This retrospective study determined survival responses to immune checkpoint inhibitors (ICIs), comparing mono- (mono) and combo-immunotherapy (combo) in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) by analyzing quantitative imaging data and clinical factors. METHODS: One hundred fifty patients were included from two centers and divided into training (n = 105) and validation (n = 45) cohorts. Radiologists manually annotated chest-abdomen-pelvis computed tomography and calculated tumor burden. Progression-free survival (PFS) was assessed, and variables were selected through Recursive Feature Elimination. Cutoff values were determined using maximally selected rank statistics to binarize features, forming a risk score with hazard ratio-derived weights. RESULTS: In total, 2258 lesions were annotated with excellent reproducibility. Key variables in the training cohort included: total tumor volume (cutoff: 73 cm3), lesion count (cutoff: 20), age (cutoff: 60) and the presence of peritoneal carcinomatosis. Their respective weights were 1.13, 0.96, 0.91, and 0.38, resulting in a risk score cutoff of 1.36. Low-score patients showed similar overall survival and PFS regardless of treatment, while those with a high-score had significantly worse survivals with mono vs combo (P = 0.004 and P = 0.0001). In the validation set, low-score patients exhibited no significant difference in overall survival and PFS with mono or combo. However, patients with a high-score had worse PFS with mono (P = 0.046). CONCLUSIONS: A score based on total tumor volume, lesion count, the presence of peritoneal carcinomatosis, and age can guide MSI-H mCRC treatment decisions, allowing oncologists to identify suitable candidates for mono and combo ICI therapies.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Estudos Retrospectivos , Reprodutibilidade dos Testes , Neoplasias do Colo/tratamento farmacológico , Instabilidade de Microssatélites , Reparo de Erro de Pareamento de DNA
20.
Diagn Interv Imaging ; 105(3): 97-103, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38261553

RESUMO

PURPOSE: The purpose of this study was to propose a deep learning-based approach to detect pulmonary embolism and quantify its severity using the Qanadli score and the right-to-left ventricle diameter (RV/LV) ratio on three-dimensional (3D) computed tomography pulmonary angiography (CTPA) examinations with limited annotations. MATERIALS AND METHODS: Using a database of 3D CTPA examinations of 1268 patients with image-level annotations, and two other public datasets of CTPA examinations from 91 (CAD-PE) and 35 (FUME-PE) patients with pixel-level annotations, a pipeline consisting of: (i), detecting blood clots; (ii), performing PE-positive versus negative classification; (iii), estimating the Qanadli score; and (iv), predicting RV/LV diameter ratio was followed. The method was evaluated on a test set including 378 patients. The performance of PE classification and severity quantification was quantitatively assessed using an area under the curve (AUC) analysis for PE classification and a coefficient of determination (R²) for the Qanadli score and the RV/LV diameter ratio. RESULTS: Quantitative evaluation led to an overall AUC of 0.870 (95% confidence interval [CI]: 0.850-0.900) for PE classification task on the training set and an AUC of 0.852 (95% CI: 0.810-0.890) on the test set. Regression analysis yielded R² value of 0.717 (95% CI: 0.668-0.760) and of 0.723 (95% CI: 0.668-0.766) for the Qanadli score and the RV/LV diameter ratio estimation, respectively on the test set. CONCLUSION: This study shows the feasibility of utilizing AI-based assistance tools in detecting blood clots and estimating PE severity scores with 3D CTPA examinations. This is achieved by leveraging blood clots and cardiac segmentations. Further studies are needed to assess the effectiveness of these tools in clinical practice.


Assuntos
Aprendizado Profundo , Embolia Pulmonar , Trombose , Humanos , Tomografia Computadorizada por Raios X/métodos , Embolia Pulmonar/diagnóstico por imagem , Ventrículos do Coração , Estudos Retrospectivos
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