Dépistage, diagnostic et pronostic

A partir de la base de données "Gene Expression Omnibus", cette étude présente une nouvelle approche bioinformatique pour identifier des biomarqueurs liés au tabagisme et au cancer du poumon

• Genetic network and gene set enrichment analysis to identify biomarkers related to cigarette smoking and lung cancer
  • Cancer treatment reviews, sous presse, 2012 (résumé)
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  A partir de la base de données "Gene Expression Omnibus", cette étude présente une nouvelle approche bioinformatique pour identifier des biomarqueurs liés au tabagisme et au cancer du poumon

  “Genetic network and gene set enrichment analysis to identify biomarkers related to cigarette smoking and lung cancer”

  • Fang, Xiaocong;Netzer, Michael;Baumgartner, Christian;Bai, Chunxue;Wang, Xiangdong

  Cigarette smoking is the most demonstrated risk factor for the development of lung cancer, while the related genetic mechanisms are still unclear. The preprocessed microarray expression dataset was downloaded from Gene Expression Omnibus database. Samples were classified according to the disease state, stage and smoking state. A new computational strategy was applied for the identification and biological interpretation of new candidate genes in lung cancer and smoking by coupling a network-based approach with gene set enrichment analysis. Network analysis was performed by pair-wise comparison according to the disease states (tumor or normal), smoking states (current smokers or nonsmokers or former smokers), or the disease stage (stages I–IV). The most activated metabolic pathways were identified by gene set enrichment analysis. Panels of top ranked gene candidates in smoking or cancer development were identified, including genes involved in cell proliferation and drug metabolism ...

  
  

Mots clés : Poumon; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Menée sur 75 patients atteints d'un mélanome métastatique, cette étude identifie, sur des lymphocytes T, des biomarqueurs associés à la réponse à un traitement par ipilimumab

• Biomarkers on melanoma patient T Cells associated with ipilimumab treatment
  • Journal of Translational Medicine, Vol. 10 (1), pp. 146, 2012 (article en libre accès)
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  Menée sur 75 patients atteints d'un mélanome métastatique, cette étude identifie, sur des lymphocytes T, des biomarqueurs associés à la réponse à un traitement par ipilimumab

  “Biomarkers on melanoma patient T Cells associated with ipilimumab treatment”

  • Wang, Wenshi;Yu, Daohai;Sarnaik, Amod;Yu, Bin;Hall, Maclean;Morelli, Dawn;Zhang, Yonghong;Zhao, Xiuhua;Weber, Jeffrey

  BACKGROUND:Ipilimumab induces long-lasting clinical responses in a minority of patients with metastatic melanoma. To better understand the mechanism(s) of action and to identify novel biomarkers associated with the clinical benefit and toxicity of ipilimumab, baseline characteristics and changes in CD4+ and CD8+ T cells from melanoma patients receiving ipilimumab were characterized by gene profiling and flow cytometry.METHODS:Microarray analysis of flow-cytometry purified CD4+ and CD8+ T cells was employed to assess gene profiling changes induced by ipilimumab. Selected molecules were further investigated by flow cytometry on pre, 3-month and 6-month post-treatment specimens.RESULTS:Ipilimumab up-regulated Ki67 and ICOS on CD4+ and CD8+ cells at both 3- and 6-month post ipilimumab (p less than or equal to 0.001), decreased CCR7 and CD25 on CD8+ at 3-month post ipilimumab (p less than or equal to 0.02), and increased Gata3 on CD4+ and CD8+ cells at 6-month post ipilimumab (p less than ...

  
  

Mots clés : Mélanome; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Menée in vivo, cette étude évalue la faisabilité d'une technique endoscopique mettant simultanément en oeuvre des modalités photoacoustique et ultrasonore pour l'imagerie des organes internes

• Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo
  • Nature Medicine, sous presse, 2012 (résumé)
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  Menée in vivo, cette étude évalue la faisabilité d'une technique endoscopique mettant simultanément en oeuvre des modalités photoacoustique et ultrasonore pour l'imagerie des organes internes

  “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo”

  • Yang, Joon-Mo;Favazza, Christopher;Chen, Ruimin;Yao, Junjie;Cai, Xin;Maslov, Konstantin;Zhou, Qifa;Shung, K. Kirk;Wang, Lihong V.

  At present, clinicians routinely apply ultrasound endoscopy in a variety of interventional procedures that provide treatment solutions for diseased organs. Ultrasound endoscopy not only produces high-resolution images, but also is safe for clinical use and broadly applicable. However, for soft tissue imaging, its mechanical wave–based image contrast fundamentally limits its ability to provide physiologically specific functional information. By contrast, photoacoustic endoscopy possesses a unique combination of functional optical contrast and high spatial resolution at clinically relevant depths, ideal for imaging soft tissues. With these attributes, photoacoustic endoscopy can overcome the current limitations of ultrasound endoscopy. Moreover, the benefits of photoacoustic imaging do not come at the expense of existing ultrasound functions; photoacoustic endoscopy systems are inherently compatible with ultrasound imaging, thereby enabling multimodality imaging with complementary ...

  
  

Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Menée sur 42 patientes atteintes d'un cancer du sein, cette étude évalue l'association entre le niveau tumoral de saturation en oxygène, mesuré par une technique de spectroscopie optique, et la réponse à une chimiothérapie néoadjuvante

• Baseline tumor oxygen saturation correlates with a pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy
  • Cancer Research, sous presse, 2012 (résumé)
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  Menée sur 42 patientes atteintes d'un cancer du sein, cette étude évalue l'association entre le niveau tumoral de saturation en oxygène, mesuré par une technique de spectroscopie optique, et la réponse à une chimiothérapie néoadjuvante

  “Baseline tumor oxygen saturation correlates with a pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy”

  • Ueda, Shigeto;Roblyer, Darren;Cerussi, Albert;Durkin, Amanda;Leproux, Anais;Santoro, Ylenia;Xu, Shanshan;O'Sullivan, Thomas D;Hsiang, David;Mehta, Rita;Butler, John;Tromberg, Bruce J

  Tissue hemoglobin oxygen saturation (i.e. oxygenation) is a functional imaging endpoint that can reveal variations in tissue hypoxia which may be predictive of pathological response in subjects undergoing Neoadjuvant Chemotherapy (NCT). In this study we used Diffuse Optical Spectroscopic Imaging (DOSI) to measure concentrations of oxyhemoglobin (ctO2Hb), deoxy-hemoglobin (ctHHb), total Hb (ctTHb = ctO2Hb + ctHHb) and oxygen saturation (stO2= ctO2Hb/ctTHb) in tumor and contralateral normal tissue from forty-one patients with locally advanced primary breast cancer. Measurements were acquired prior to the start of neoadjuvant chemotherapy. Optically derived parameters were analyzed separately and in combination with clinical biomarkers to evaluate correlations with pathologic response. Discriminant analysis was performed to determine the ability of optical and clinical biomarkers to classify subjects into response groups. Twelve (28.6%) of 42 tumors achieved pCR and 30 (71.4%) were ...

  
  

Mots clés : Sein; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Menée sur 165 patients atteints d'un cancer avancé du poumon non à petites cellules, cette étude évalue et compare les performances de cinq tests de détection d'une mutation du gène EGFR

• An evaluation study of EGFR mutation tests utilized for non-small-cell lung cancer in the diagnostic setting
  • Annals of Oncology, sous presse, 2012 (résumé)
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  Menée sur 165 patients atteints d'un cancer avancé du poumon non à petites cellules, cette étude évalue et compare les performances de cinq tests de détection d'une mutation du gène EGFR

  “An evaluation study of EGFR mutation tests utilized for non-small-cell lung cancer in the diagnostic setting”

  • Goto, K.;Satouchi, M.;Ishii, G.;Nishio, K.;Hagiwara, K.;Mitsudomi, T.;Whiteley, J.;Donald, E.;McCormack, R.;Todo, T.

  Background Epidermal growth factor receptor (EGFR) mutation is predictive for the efficacy of EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC) treatment. We evaluated the performance, sensitivity, and concordance between five EGFR tests.Materials and methods DNA admixtures (n = 34; 1%–50% mutant plasmid DNA) and samples from NSCLC patients [116 formalin-fixed paraffin-embedded (FFPE) tissue, 29 matched bronchofiberscopic brushing (BB) cytology, and 20 additional pleural effusion (PE) cytology samples] were analyzed. EGFR mutation tests were PCR-Invader®, peptide nucleic acid-locked nucleic acid PCR clamp, direct sequencing, Cycleave™, and Scorpion Amplification Refractory Mutation System (ARMS)®. Analysis success, mutation status, and concordance rates were assessed.Results All tests except direct sequencing detected four mutation types at ≥1% mutant DNA. Analysis success rates were 91.4%–100% (FFPE) and 100% (BB and PE cytology), ...

  
  

Mots clés : Poumon; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Menée sur une cohorte initiale de 381 patients atteints d'un cancer colorectal, puis validée sur une cohorte de 80 patients et une base de données portant sur des patients atteints d'un cancer colorectal métastatique traité à l'aide de cetuximab, cette étude évalue l'association entre une signature basée sur l'expression de gènes mutés (KRAS, BRAF et PIK3CA) et la réponse au cetuximab

• A combined oncogenic pathway signature of BRAF, KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction
  • Gut, sous presse, 2012 (résumé)
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  Menée sur une cohorte initiale de 381 patients atteints d'un cancer colorectal, puis validée sur une cohorte de 80 patients et une base de données portant sur des patients atteints d'un cancer colorectal métastatique traité à l'aide de cetuximab, cette étude évalue l'association entre une signature basée sur l'expression de gènes mutés (KRAS, BRAF et PIK3CA) et la réponse au cetuximab

  “A combined oncogenic pathway signature of BRAF, KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction”

  • Tian, Sun;Simon, Iris;Moreno, Victor;Roepman, Paul;Tabernero, Josep;Snel, Mireille;van't Veer, Laura;Salazar, Ramon;Bernards, Rene;Capella, Gabriel

  Objective To develop gene expression profiles that characterise KRAS-, BRAF- or PIK3CA-activated- tumours, and to explore whether these profiles might be helpful in predicting the response to the epidermal growth factor receptor (EGFR) pathway inhibitors better than mutation status alone.Design Fresh frozen tumour samples from 381 colorectal cancer (CRC) patients were collected and mutations in KRAS, BRAF and PIK3CA were assessed. Using microarray data, three individual oncogenic and a combined model were developed and validated in an independent set of 80 CRC patients, and in a dataset from metastatic CRC patients treated with cetuximab.Results 175 tumours (45.9%) harboured oncogenic mutations in KRAS (30.2%), BRAF (11.0%) and PIK3CA (11.5%). Activating mutation signatures for KRAS (75 genes), for BRAF (58 genes,) and for PIK3CA (49 genes) were developed. The development of a combined oncogenic pathway signature-classified tumours as ‘activated oncogenic’, or as ...

  
  

Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Cet article passe en revue les signatures d'expression de gènes permettant de prédire la réponse à une chimiothérapie adjuvante chez les patients atteints d'un cancer du côlon de stade II

• Gene Signatures in Stage II Colon Cancer: A Clinical Review
  • Current Colorectal Cancer Reports, sous presse, 2012 (résumé)
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  Cet article passe en revue les signatures d'expression de gènes permettant de prédire la réponse à une chimiothérapie adjuvante chez les patients atteints d'un cancer du côlon de stade II

  “Gene Signatures in Stage II Colon Cancer: A Clinical Review”

  • Sharif, Saima;O’Connell, Michael

  Understanding the biology of cancer is the key to understanding its behavior. Stage II colon cancers represent a unique treatment challenge for medical oncologists because they contain a very heterogeneous group of tumors with a wide range of recurrence risks after resection. Defining these differences in biology can help to explain differences in disease behavior. To this end, gene signatures have been developed to define various prognostic groups beyond the clinicopathologic features alone. Adjuvant chemotherapy for stage II colon cancers as a group has not shown survival advantage in clinical trials. Future research to develop gene signatures to predict a group that will benefit from adjuvant chemotherapy will be helpful in the clinical decision-making process. The purpose of this review is to present the prognostic gene signatures currently available for use, those in development, and their utility in stratifying recurrence risk in stage II colon cancer patients.

  
  

Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Menée sur des échantillons de plasma et d'urine, cette étude évalue les performances d'une méthode de protéomique ciblée pour quantifier de façon reproductible des protéines associées au cancer

• Reproducible Quantification of Cancer-Associated Proteins in Body Fluids Using Targeted Proteomics
  • Science Translational Medicine, Vol. 4 (142), pp. 142ra94, 2012 (résumé)
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  Menée sur des échantillons de plasma et d'urine, cette étude évalue les performances d'une méthode de protéomique ciblée pour quantifier de façon reproductible des protéines associées au cancer

  “Reproducible Quantification of Cancer-Associated Proteins in Body Fluids Using Targeted Proteomics”

  • Hüttenhain, Ruth;Soste, Martin;Selevsek, Nathalie;Röst, Hannes;Sethi, Atul;Carapito, Christine;Farrah, Terry;Deutsch, Eric W.;Kusebauch, Ulrike;Moritz, Robert L.;Niméus-Malmström, Emma;Rinner, Oliver;Aebersold, Ruedi

  The rigorous testing of hypotheses on suitable sample cohorts is a major limitation in translational research. This is particularly the case for the validation of protein biomarkers; the lack of accurate, reproducible, and sensitive assays for most proteins has precluded the systematic assessment of hundreds of potential marker proteins described in the literature. Here, we describe a high-throughput method for the development and refinement of selected reaction monitoring (SRM) assays for human proteins. The method was applied to generate such assays for more than 1000 cancer-associated proteins, which are functionally related to candidate cancer driver mutations. We used the assays to determine the detectability of the target proteins in two clinically relevant samples: plasma and urine. One hundred eighty-two proteins were detected in depleted plasma, spanning five orders of magnitude in abundance and reaching below a concentration of 10 ng/ml. The narrower concentration range of ...

  
  

Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Menée sur 166 patients atteints d'un cancer des voies biliaires extra-hépatiques (120 hommes et 46 femmes ; âge : 34 à 86 ans ; durée médiane de suivi : 29 mois), cette étude identifie les facteurs histopathologiques associés au risque de métastases à distance après un traitement combinant une résection curative et une chimioradiothérapie adjuvante

• Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer
  • International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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  Menée sur 166 patients atteints d'un cancer des voies biliaires extra-hépatiques (120 hommes et 46 femmes ; âge : 34 à 86 ans ; durée médiane de suivi : 29 mois), cette étude identifie les facteurs histopathologiques associés au risque de métastases à distance après un traitement combinant une résection curative et une chimioradiothérapie adjuvante

  “Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer”

  • Kim, Kyubo;Chie, Eui Kyu;Jang, Jin-Young;Kim, Sun Whe;Han, Sae-Won;Oh, Do-Youn;Im, Seock-Ah;Kim, Tae-You;Bang, Yung-Jue;Ha, Sung W.

  To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34–86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34–56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up duration was 29 months. The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, ...

  
  

Mots clés : Voies biliaires; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée dans l'Est et le Sud de la Chine sur 1 853 patientes atteintes d'un cancer du sein et sur 1 992 témoins, cette étude montre qu'un polymorphisme à simple nucléotide du gène codant pour la protéine CD44 (rs13347 C>T) est associé au risque de cancer du sein et à la survie des patientes

• CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations
  • Breast Cancer Research, Vol. 14 (4), pp. R105, 2012 (résumé)
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  Menée dans l'Est et le Sud de la Chine sur 1 853 patientes atteintes d'un cancer du sein et sur 1 992 témoins, cette étude montre qu'un polymorphisme à simple nucléotide du gène codant pour la protéine CD44 (rs13347 C>T) est associé au risque de cancer du sein et à la survie des patientes

  “CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations”

  • Jiang, Lan;Deng, Jieqiong;Zhu, Xun;Zheng, Jian;You, Yonghe;Li, Na;Wu, Hongchun;Lu, Jiachun;Zhou, Yifeng

  INTRODUCTION:It has been demonstrated that the interplay of adhesion molecule CD44 and its ligands can regulate cancer cell proliferation, migration, and invasion, as well as tumor-associated angiogenesis and is related to breast cancer patient survival. In this two-stage case control study, we determined whether common functional tagSNPs are associated with breast cancer risk and prognosis.METHODS:Five tagSNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were selected and genotyped in 1853 breast cancer patients and 1992 healthy control subjects in Eastern and Southern populations. Potential function of rs13347C>T and association between this variation and breast cancer were further studied.RESULTS:Compared with the most common rs13347CC genotype, variant genotypes (CT and TT) increased individual's susceptibility to breast cancer, especially in estrogen receptor (ER) negative patients (OR=1.37, 95%CI=1.17-1.59 for ER positive patients; OR=2.37, ...

  
  

Mots clés : Sein; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

A partir de 264 ganglions sentinelles prélevés sur 131 patientes atteintes d'un cancer du sein, cette étude évalue la sensibilité, la spécificité et la rapidité d'un test reposant sur la mesure conjointe du nombre de copies de l'ARN messager de la cytokératine-19 et de l'antigène carcinoembryonnaire pour détecter des métastases

• Accurate and rapid novel genetic diagnosis for detection of sentinel lymph node metastasis in breast cancer patients
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  A partir de 264 ganglions sentinelles prélevés sur 131 patientes atteintes d'un cancer du sein, cette étude évalue la sensibilité, la spécificité et la rapidité d'un test reposant sur la mesure conjointe du nombre de copies de l'ARN messager de la cytokératine-19 et de l'antigène carcinoembryonnaire pour détecter des métastases

  “Accurate and rapid novel genetic diagnosis for detection of sentinel lymph node metastasis in breast cancer patients”

  • Iinuma, H.;Tamura, J.;Omoto, D.;Kamo, N.;Ohnaka, S.;Mitoma, Y.;Miyazawa, Y.;Okinaga, K.;Imamura, T.;Fukushima, R.;Watanabe, T.;Ikeda, T.

  Background : The transcription-reverse transcription concerted reaction (TRC) test is a novel molecular-based procedure, which can assess nodal metastasis accurately and quickly. We examined the usefulness of the TRC test with a double marker, cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA, to detect sentinel lymph nodes (SLN) metastasis in breast cancer patients. Methods : A total of 264 SLNs from 131 breast cancer patients were assigned to a training set (109 SLNs from 50 patients) and validation set (155 SLNs from 81 patients). Cytokeratin 19 and CEA mRNA were detected by TRC tests, and the sensitivity and specificity of the SLN metastasis between the TRC and histology cohorts were compared. Results : Mean copy numbers of CK19 and CEA by TRC tests were increased according to the metastatic size. In the training set, TRC test showed 100% sensitivity, specificity and concordance rates against the permanent histopathology test. In the validation set, sensitivity was ...

  
  

Mots clés : Sein; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 1 478 patientes atteintes d'un cancer du sein de stade précoce et traitées, entre 1980 et 2007, par chirurgie conservatrice et par radiothérapie combinée ou non à un traitement systémique, cette étude montre qu'une invasion tumorale lymphovasculaire n'est pas associée de façon indépendante à la récidive loco-régionale de la maladie et à la survie des patientes

• Lymphatic Space Invasion is Not an Independent Predictor of Outcomes in Early Stage Breast Cancer Treated by Breast-Conserving Surgery and Radiation
  • The Breast Journal, sous presse, 2012 (résumé)
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  Menée sur 1 478 patientes atteintes d'un cancer du sein de stade précoce et traitées, entre 1980 et 2007, par chirurgie conservatrice et par radiothérapie combinée ou non à un traitement systémique, cette étude montre qu'une invasion tumorale lymphovasculaire n'est pas associée de façon indépendante à la récidive loco-régionale de la maladie et à la survie des patientes

  “Lymphatic Space Invasion is Not an Independent Predictor of Outcomes in Early Stage Breast Cancer Treated by Breast-Conserving Surgery and Radiation”

  • Freedman, Gary M.;Li, Tianyu;Polli, Leonardo V.;Anderson, Penny R.;Bleicher, Richard J.;Sigurdson, Elin;Swaby, Ramona;Dushkin, Holly;Patchefsky, Arthur;Goldstein, Lori

  Abstract: To study the prognostic importance of lymphovascular invasion (LVI) in early stage breast cancer after conservative surgery and radiation. From 2/80 to 8/07, 1,478 patients were treated with breast-conserving surgery and radiation with or without systemic therapy. Study eligibility included breast conservation, whole breast postoperative radiation, T1–T2 disease, and known LVI status. Endpoints were 5- and 10-year actuarial outcomes for local control and survival. LVI was present in 427 patients and absent in 1,051 patients. Median follow-up was 68 and 69 months, respectively. Patients with LVI had a younger median age, were more often pre- or perimenopausal, T2, physically palpable, invasive ductal, node positive, grade 3, and treated with chemotherapy compared with patients without LVI. The 5- and 10-year local-regional recurrence was 4.5% and 9.6% with LVI compared with 1.6% and 5.6% without LVI (p = 0.01). The 5- and 10-year overall survival was 83% and 68% for LVI ...

  
  

Mots clés : Sein; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

A partir d'une revue systématique de la littérature (6 études, 527 patients), cette méta-analyse évalue la sensibilité et la spécificité d'une élastographie ultrasonore transrectale pour détecter un cancer de la prostate

• Transrectal sonoelastography in the detection of prostate cancers: a meta-analysis
  • BJU International, sous presse, 2012 (résumé)
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  A partir d'une revue systématique de la littérature (6 études, 527 patients), cette méta-analyse évalue la sensibilité et la spécificité d'une élastographie ultrasonore transrectale pour détecter un cancer de la prostate

  “Transrectal sonoelastography in the detection of prostate cancers: a meta-analysis”

  • Teng, Jingfei;Chen, Ming;Gao, Yi;Yao, Yacheng;Chen, Lu;Xu, Danfeng

  Study Type – Diagnostic (exploratory cohort)Level of Evidence 3aWhat's known on the subject? and What does the study add?The accuracy of transrectal sonoelastography (TRSE) in the detection of prostate cancer is variable, with a sensitivity ranging from 51.1 to 91.7% and specificity ranging from 62.2 to 86.8%.This is the first meta-analysis to assess the overall accuracy of TRSE in the detection of prostate cancer. OBJECTIVE * •To assess the overall accuracy of transrectal sonoelastography (TRSE) targeted biopsy in the diagnosis of patients suspected of having prostate cancer (PCa). METHODS * •A systematic search of electronic databases, including PubMed, Embase and The Cochrane Library, and manual bibliography searches were performed. * •All relevant studies assessing the diagnostic accuracy of TRSE in PCa detection were included in our meta-analysis. * •The data were pooled and sensitivity, specificity, area under the curve (AUC), positive likelihood ratio (LR) and ...

  
  

Mots clés : Prostate; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 323 hommes japonais présentant des niveaux élevés du PSA et dont l'examen de la prostate par toucher rectal est anormal, cette étude montre une association entre un faible niveau sérique de neutrophiles et le résultat positif d'une biopsie prostatique à l'aiguille

• Low serum neutrophil count predicts a positive prostate biopsy
  • Prostate Cancer and Prostatic Diseases, sous presse, 2012 (résumé)
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  Menée sur 323 hommes japonais présentant des niveaux élevés du PSA et dont l'examen de la prostate par toucher rectal est anormal, cette étude montre une association entre un faible niveau sérique de neutrophiles et le résultat positif d'une biopsie prostatique à l'aiguille

  “Low serum neutrophil count predicts a positive prostate biopsy”

  • Fujita, K.;Imamura, R.;Tanigawa, G.;Nakagawa, M.;Hayashi, T.;Kishimoto, N.;Hosomi, M.;Yamaguchi, S.

  Background :Asymptomatic prostatic inflammation may cause increased PSA in some men, leading to unnecessary prostate biopsy. We investigated whether the differential white cell count could predict the result of prostate biopsy. Methods : Prostate needle biopsy was carried out in 323 Japanese men with elevated PSA levels or abnormal digital rectal findings. White blood cell count (WBC), differential white cell count (neutrophils, lymphocytes, basophils, eosinophils, and monocytes), and serum C-reactive protein level were assessed for associations with biopsy findings. Results : In all, 203 (62.1%) were positive for prostate cancer. WBC, neutrophil count, age, PSA, prostate volume, and PSA density (PSAD) were associated with the results of biopsy (P<0.05). Multivariate analysis showed that neutrophil count, age, PSA, prostate volume and PSAD were independent predictors. When the cut-off neutrophil count was set at 2900  μl −1, 78 of 104 men (75.0%) with a count below this value had ...

  
  

Mots clés : Prostate; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur une cohorte de 4 569 patients atteints d'un cancer de la prostate traité par prostatectomie radicale entre 1982 et 2011, cette étude rétrospective évalue, par rapport à différentes variables clinicopathologiques (score de Gleason, niveaux du PSA, stade de la maladie au diagnostic) et du point de vue de la mortalité spécifique, la valeur prédictive d'une marge de résection positive

• Impact of surgical margin status on prostate-cancer-specific mortality
  • BJU International, sous presse, 2012 (résumé)
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  Menée sur une cohorte de 4 569 patients atteints d'un cancer de la prostate traité par prostatectomie radicale entre 1982 et 2011, cette étude rétrospective évalue, par rapport à différentes variables clinicopathologiques (score de Gleason, niveaux du PSA, stade de la maladie au diagnostic) et du point de vue de la mortalité spécifique, la valeur prédictive d'une marge de résection positive

  “Impact of surgical margin status on prostate-cancer-specific mortality”

  • Chalfin, Heather J.;Dinizo, Michael;Trock, Bruce J.;Feng, Zhaoyong;Partin, Alan W.;Walsh, Patrick C.;Humphreys, Elizabeth;Han, Misop

  Study Type – Diagnostic (exploratory cohort)Level of Evidence 2bWhat's known on the subject? and What does the study add?Surgical margin status at radical prostatectomy (RP) has been shown to be a predictor of disease progression and the strongest predictor of benefit from adjuvant therapy, but the impact of a positive surgical margin (PSM) on long-term prostate-cancer-specific survival is unknown. The PSM rate is dependent on the pathological stage of the cancer. In a recent multicentre nomogram for 15-year prostate-cancer-specific mortality (PCSM) after RP, PSM was not significantly associated with PCSM, while Gleason score and pathological stage were the only significant predictors. This has not been validated in a single centre, and PSM has been shown to vary greatly with surgical technique.This is the first study on the impact of PSM on PCSM in a single surgeon's cohort.In other centres, the decision to administer adjuvant therapy may be influenced by surgical margin status. ...

  
  

Mots clés : Prostate; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Cet article décrit les recommandations de l'American Society of Clinical Oncology concernant l'utilisation du dosage de l'antigène prostatique spécifique pour détecter un cancer de la prostate

• Screening for Prostate Cancer With Prostate-Specific Antigen Testing: American Society of Clinical Oncology Provisional Clinical Opinion
  • Journal of Clinical Oncology, sous presse, 2012 (article en libre accès)
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  Cet article décrit les recommandations de l'American Society of Clinical Oncology concernant l'utilisation du dosage de l'antigène prostatique spécifique pour détecter un cancer de la prostate

  “Screening for Prostate Cancer With Prostate-Specific Antigen Testing: American Society of Clinical Oncology Provisional Clinical Opinion”

  • Basch, Ethan;Oliver, Thomas K.;Vickers, Andrew;Thompson, Ian;Kantoff, Philip;Parnes, Howard;Loblaw, D. Andrew;Roth, Bruce;Williams, James;Nam, Robert K.

  Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer.Clinical Context Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection.Recent Data Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic.Results In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, ...

  
  

Mots clés : Prostate; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 855 patients atteints d'un mélanome avec métastases distantes, cette étude montre une association entre les niveaux sériques de la lactate déshydrogénase ou de la protéine S100B et la survie à 5 ans des patients

• Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  Menée sur 855 patients atteints d'un mélanome avec métastases distantes, cette étude montre une association entre les niveaux sériques de la lactate déshydrogénase ou de la protéine S100B et la survie à 5 ans des patients

  “Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis”

  • Weide, B.;Elsasser, M.;Buttner, P.;Pflugfelder, A.;Leiter, U.;Eigentler, T. K.;Bauer, J.;Witte, M.;Meier, F.;Garbe, C.

  Background : Established prognostic factors are of limited value to predict long-term survival and benefit from metastasectomy in advanced melanoma. This study aimed to identify prognostic factors in patients with distant metastasis. Methods : We analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan–Meier survival probabilities and multivariate Cox hazard regression analysis. Results : Serum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses. Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival. Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis. This treatment ...

  
  

Mots clés : Mélanome; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

A partir d'échantillons de moelle osseuse prélevés sur 230 patients pédiatriques atteints d'une leucémie myéloïde aiguë, cette étude montre qu'un niveau élevé d'expression du facteur de transcription GATA2 est associé à un pronostic défavorable

• High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia
  • Blood, sous presse, 2012 (résumé)
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  A partir d'échantillons de moelle osseuse prélevés sur 230 patients pédiatriques atteints d'une leucémie myéloïde aiguë, cette étude montre qu'un niveau élevé d'expression du facteur de transcription GATA2 est associé à un pronostic défavorable

  “High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia”

  • Luesink, Maaike;Hollink, Iris H.I.M.;van der Velden, Vincent H.J.;Knops, Ruth H.J.N.;Boezeman, Jan B.M.;de Haas, Valérie;Trka, Jan;Baruchel, Andre;Reinhardt, Dirk;van der Reijden, Bert A.;van den Heuvel-Eibrink, Marry M.;Zwaan, C. Michel;Jansen, Joop H.

  In acute myeloid leukemia (AML), aberrant expression and mutations of transcription factors have been correlated with disease outcome. In de novo pediatric AML patients, we performed expression and mutation screening of GATA2, which is an essential transcription factor for regulation of myeloid lineage determination. GATA2 mutations were detected in 5/230 patients, representing a frequency of 2.2% overall, and 9.8% in cytogenetically normal AML. GATA2 expression analysis demonstrated that in 155/237 diagnostic samples (65%), GATA2 expression was higher than in normal bone marrow. In complete remission, normalization of GATA2 expression was observed, whereas GATA2 expression levels stayed high in patients with resistant disease. Importantly, high GATA2 expression at diagnosis was an independent poor prognostic factor for overall survival (HR 1.7, p=0.045), event free survival (HR 2.1, p=0.002), and disease free survival (HR 2.3, p=0.004). The prognostic impact of GATA2 was particularly ...

  
  

Mots clés : Leucémie; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Couplée à l'étude "Singapore Chinese Health", cette étude cas-témoins évalue l'association entre le nombre de copies de l'ADN mitochondrial dans le sang périphérique et le risque de développer un cancer colorectal (422 cas et 874 témoins)

• Mitochondrial copy number is associated with colorectal cancer risk
  • Cancer Epidemiology Biomarkers & Prevention, sous presse, 2012 (résumé)
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  Couplée à l'étude "Singapore Chinese Health", cette étude cas-témoins évalue l'association entre le nombre de copies de l'ADN mitochondrial dans le sang périphérique et le risque de développer un cancer colorectal (422 cas et 874 témoins)

  “Mitochondrial copy number is associated with colorectal cancer risk”

  • Thyagarajan, Bharat;Wang, Renwei;Barcelo, Helene;Koh, Woon-Puay;Yuan, Jian-Min

  Background : Mitochondria are eukaryotic organelles responsible for energy production. Quantitative changes in human mitochondrial DNA (mtDNA) copy number have been implicated in various cancer types. Data from prospective cohort studies on mtDNA copy number and colorectal cancer risk have been lacking. Methods:We evaluated the association between mtDNA copy number in peripheral blood and colorectal cancer risk in a nested case-control study of 422 colorectal cancer cases (168 cases with pre-diagnostic blood and 254 cases with post-diagnostic blood) and 874 controls who were free of colorectal cancer among participants of the Singapore Chinese Health Study. The relative mtDNA copy number was measured using real time PCR. Unconditional logistic regression methods were employed to examine the association between mtDNA copy number and colorectal cancer risk. Results:There was a U-shaped relationship between the relative mtDNA copy number and colorectal cancer risk. Compared with the 2nd ...

  
  

Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

A partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 277 patients atteints d'un cancer colorectal, cette étude prospective montre que l'expression d'un inducteur des métalloprotéases matricielles est associée à l'expression de S100A4 et au pronostic de la maladie

• EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  A partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 277 patients atteints d'un cancer colorectal, cette étude prospective montre que l'expression d'un inducteur des métalloprotéases matricielles est associée à l'expression de S100A4 et au pronostic de la maladie

  “EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer”

  • Boye, K.;Nesland, J. M.;Sandstad, B.;Haugland Haugen, M.;Malandsmo, G. M.;Flatmark, K.

  Background : Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. Methods :The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. Results : One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. ...

  
  

Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 114 patients adultes ayant survécu à un cancer pédiatrique (âge : 22 à 53 ans) et ayant été exposés à une chimiothérapie à base d'antracyclines et/ou à une radiothérapie thoracique, cette étude transversale évalue la sensibilité et la spécificité d'une IRM cardiaque et d'une échocardiographie pour détecter une cardiomyopathie

• Screening Adult Survivors of Childhood Cancer for Cardiomyopathy: Comparison of Echocardiography and Cardiac Magnetic Resonance Imaging
  • Journal of Clinical Oncology, sous presse, 2012 (résumé)
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  Menée sur 114 patients adultes ayant survécu à un cancer pédiatrique (âge : 22 à 53 ans) et ayant été exposés à une chimiothérapie à base d'antracyclines et/ou à une radiothérapie thoracique, cette étude transversale évalue la sensibilité et la spécificité d'une IRM cardiaque et d'une échocardiographie pour détecter une cardiomyopathie

  “Screening Adult Survivors of Childhood Cancer for Cardiomyopathy: Comparison of Echocardiography and Cardiac Magnetic Resonance Imaging”

  • Armstrong, Gregory T.;Plana, Juan Carlos;Zhang, Nan;Srivastava, Deokumar;Green, Daniel M.;Ness, Kirsten K.;Donovan, F. Daniel;Metzger, Monika L.;Arevalo, Alejandro;Durand, Jean-Bernard;Joshi, Vijaya;Hudson, Melissa M.;Robison, Leslie L.;Flamm, Scott D.

  Purpose To compare two-dimensional (2D) echocardiography, the current method of screening for treatment-related cardiomyopathy recommended by the Children’s Oncology Group Guidelines, to cardiac magnetic resonance (CMR) imaging, the reference standard for left ventricular (LV) function.Patients and Methods Cross-sectional, contemporaneous evaluation of LV structure and function by 2D and three-dimensional (3D) echocardiography and CMR imaging in 114 adult survivors of childhood cancer currently median age 39 years (range, 22 to 53 years) exposed to anthracycline chemotherapy and/or chest-directed radiation therapy.Results In this survivor population, 14% (n = 16) had an ejection fraction (EF) less than 50% by CMR. Survivors previously undiagnosed with cardiotoxicity (n = 108) had a high prevalence of EF (32%) and cardiac mass (48%) that were more than two standard deviations below the mean of normative CMR data. 2D echocardiography overestimated the mean EF of this population by 5%. ...

  
  

Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Cet article analyse les travaux récents invitant à réévaluer le rapport bénéfices/risques des programmes de dépistage du cancer du sein

• Is the tide turning against breast screening?
  • Breast Cancer Research, Vol. 14 (4), pp. 107, 2012 (éditorial en libre accès)
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  Cet article analyse les travaux récents invitant à réévaluer le rapport bénéfices/risques des programmes de dépistage du cancer du sein

  “Is the tide turning against breast screening?”

  • Jorgensen, Karsten

  Herein I argue that mammographic screening has not delivered on its fundamental premise: to reduce the incidence of advanced breast cancer. Indeed, achieving this goal is required if screening is to reduce breast cancer mortality or mastectomy use. Rather, screening has caused substantial increases in the incidence of in situ and early invasive cancers. Moreover, evidence indicates that these screen-detected cancers are unlikely to be cases that were 'caught early', but instead represent women who would not have been diagnosed in the absence of screening and who, as a result, have received harmful, unnecessary treatment. If true, these observations raise the specter that screening creates breast cancer patients and that this practice carries little or no benefit.

  
  

Mots clés : Sein; Dépistage, diagnostic et pronostic (Politiques et programmes de dépistage)

Cette étude évalue les performances d’une technique de séquençage du génome entier à partir d’un échantillon ne comprenant pas plus de 10 à 20 cellules

• Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells
  • Nature, Vol. 487 (7406), pp. 190-195, 2012 (résumé)
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  Cette étude évalue les performances d’une technique de séquençage du génome entier à partir d’un échantillon ne comprenant pas plus de 10 à 20 cellules

  “Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells”

  • Peters, Brock A.;Kermani, Bahram G.;Sparks, Andrew B.;Alferov, Oleg;Hong, Peter;Alexeev, Andrei;Jiang, Yuan;Dahl, Fredrik;Tang, Y. Tom;Haas, Juergen;Robasky, Kimberly;Zaranek, Alexander Wait;Lee, Je-Hyuk;Ball, Madeleine Price;Peterson, Joseph E.;Perazich, Helena;Yeung, George;Liu, Jia;Chen, Linsu;Kennemer, Michael I.;Pothuraju, Kaliprasad;Konvicka, Karel;Tsoupko-Sitnikov, Mike;Pant, Krishna P.;Ebert, Jessica C.;Nilsen, Geoffrey B.;Baccash, Jonathan;Halpern, Aaron L.;Church, George M.;Drmanac, Radoje

  Recent advances in whole-genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, long fragment read (LFR) technology, which is similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 picograms of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants were assembled into long haplotype contigs. Removal of false positive single nucleotide variants not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 megabases. Cost-effective and accurate genome sequencing and haplotyping from 10–20 human cells, as demonstrated here, will enable comprehensive genetic ...

  
  

Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

Cet article décrit le programme français des plateformes hospitalières de génétique moléculaire

• Tumour molecular profiling for deciding therapy - the French initiative
  • Nature Reviews Clinical Oncology, sous presse, 2012 (résumé)
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  Cet article décrit le programme français des plateformes hospitalières de génétique moléculaire

  “Tumour molecular profiling for deciding therapy - the French initiative”

  • Nowak, Frederique;Soria, Jean-Charles;Calvo, Fabien

  The use of tumour molecular profiles for therapeutic decision making requires that molecular diagnostics be introduced into routine clinical practice. To this end, the French National Cancer Institute and French Ministry of Health have set up a national network of 28 regional molecular genetics centres. These facilities perform selected molecular tests, free of charge, for all patients in their region, regardless of the institution where they are treated. A specific programme has also been implemented to anticipate the launch of new targeted treatments and reduce time-to-access to new drugs and experimental therapies. In 2011, 55,000 patients with cancer in France benefited from molecular predictive tests. The French nationwide initiative for tumour molecular profiling is a tool to fight inequalities in access to molecular testing and targeted therapy, and demonstrates that molecular stratification of tumours for therapeutic decisions is a cost-effective strategy that can be ...

  
  

Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))