Dépistage, diagnostic et pronostic

Menée sur des lignées cellulaires et un modèle murin, cette étude suggère que le niveau d'expression de l'ARN messager du gène ZNF217, qui favorise la transition épithélio-mésenchymateuse, pourrait servir de biomarqueur pour le pronostic d'un cancer du sein

• ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchyme transition and invasion
  • Cancer Research, sous presse, 2012 (résumé)
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  Menée sur des lignées cellulaires et un modèle murin, cette étude suggère que le niveau d'expression de l'ARN messager du gène ZNF217, qui favorise la transition épithélio-mésenchymateuse, pourrait servir de biomarqueur pour le pronostic d'un cancer du sein

  “ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchyme transition and invasion”

  • Vendrell, Julie A.;Thollet, Aurélie;Nguyen, Nhan T;Ghayad, Sandra E;Vinot, Stéphanie;Biéche, Ivan;Grisard, Evelyne;Josserand, Véronique;Coll, Jean-Luc;Roux, Pierre;Corbo, Laura;Treilleux, Isabelle;Rimokh, Ruth;Cohen, Pascale A

  The Krüppel-like zinc-finger protein ZNF217 is a candidate oncogene in breast cancer. In this study, we demonstrated that high levels of expression of ZNF217 mRNA are associated with poor prognosis and the development of metastases in breast cancer. Overexpression of ZNF217 in breast cancer cells stimulated migration and invasion in vitro and promoted the development of spontaneous lung or node metastases in mice in vivo. ZNF217 also promoted epithelial-mesenchymal transition (EMT) in human mammary epithelial cells, and the TGF-β-activated Smad signaling pathway was identified as a major driver of ZNF217-induced EMT. In addition, a TGF-β autocrine loop sustained activation of the TGF-β pathway in ZNF217-overexpressing mammary epithelial cells, most likely due to ZNF217-mediated direct up-regulation of TGFB2 or TGFB3. Inhibition of the TGF-β pathway led to the reversal of ZNF217-mediated EMT. Together, our findings indicate that ZNF217 mRNA expression may represent a novel ...

  
  

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

Menée in vitro et in vivo, cette étude suggère que le niveau d'expression du facteur de transcription Fra-1 est associé à la réponse à une chimiothérapie dans le cancer du sein

• Fra-1 promotes breast cancer chemosensitivity by driving cancer stem cells from dormancy
  • Cancer Research, sous presse, 2012 (résumé)
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  Menée in vitro et in vivo, cette étude suggère que le niveau d'expression du facteur de transcription Fra-1 est associé à la réponse à une chimiothérapie dans le cancer du sein

  “Fra-1 promotes breast cancer chemosensitivity by driving cancer stem cells from dormancy”

  • Lu, Dan;Chen, Si;Tan, Xiaoyue;Li, Na;Liu, Chenghu;Li, Zongjin;Liu, Ze;Stupack, Dwayne G;Reisfeld, Ralph A.;Xiang, Rong

  Fra-1 is a member of the Fos transcription factor family that is highly expressed in multiple cancers, playing important roles in transformation, proliferation and metastasis. In this study, we observed an inverse correlation between the expression of Fra-1 in human stage II breast cancer tissues and the corresponding level of clinical chemoresistance. Extending these findings in vitro, we found that knockdown of Fra-1 in breast tumor cells was sufficient to confer resistance to doxorubicin and cyclophosphamide, while enhanced Fra-1 expression could render these cells chemosensitive. The tumor cell 'side population' (SP), which is enriched for cancer stem-like cells, was found to be associated with chemoresistance. Increased SP fractions were detected among tumor cell lines subjected to Fra-1 knockdown. In contrast, enhanced expression of Fra-1 was correlated with a decreased SP fraction, and significantly, this finding was recapitulated in vivo, where tumors with enhanced expression ...

  
  

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

Menée sur une cohorte de 40 patients atteints d'un carcinome rénal métastatique à cellules claires, cette étude évalue l'association entre une signature fondée sur l'expression de 4 micro-ARNs et le pronostic de la maladie

• Identification of a 4-microRNA Signature for Clear Cell Renal Cell Carcinoma Metastasis and Prognosis
  • PLoS ONE, Vol. 7 (5), pp. e35661, 2012 (article en libre accès)
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  Menée sur une cohorte de 40 patients atteints d'un carcinome rénal métastatique à cellules claires, cette étude évalue l'association entre une signature fondée sur l'expression de 4 micro-ARNs et le pronostic de la maladie

  “Identification of a 4-microRNA Signature for Clear Cell Renal Cell Carcinoma Metastasis and Prognosis”

  • Wu, Xiwei;Weng, Lihong;Li, Xuejun;Guo, Chao;Pal, Sumanta K.;Jin, Jennifer M.;Li, Yuping;Nelson, Rebecca A.;Mu, Bing;Onami, Susan H.;Wu, Jeffrey J.;Ruel, Nora H.;Wilczynski, Sharon P.;Gao, Hanlin;Covarrubias, Maricela;Figlin, Robert A.;Weiss, Lawrence M.;Wu, Huiqing

  Renal cell carcinoma (RCC) metastasis portends a poor prognosis and cannot be reliably predicted. Early determination of the metastatic potential of RCC may help guide proper treatment. We analyzed microRNA (miRNA) expression in clear cell RCC (ccRCC) for the purpose of developing a miRNA expression signature to determine the risk of metastasis and prognosis. We used the microarray technology to profile miRNA expression of 78 benign kidney and ccRCC samples. Using 28 localized and metastatic ccRCC specimens as the training cohort and the univariate logistic regression and risk score methods, we developed a miRNA signature model in which the expression levels of miR-10b, miR-139-5p, miR-130b and miR-199b-5p were used to determine the status of ccRCC metastasis. We validated the signature in an independent 40-sample testing cohort of different stages of primary ccRCCs using the microarray data. Within the testing cohort patients who had at least 5 years follow-up if no metastasis ...

  
  

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

Menée sur 36 patients atteints d'un cancer de la prostate, cette étude prospective analyse l'évolution de 292 métabolites après 3 mois d'un traitement anti-androgénique

• Prospective study of changes in the metabolomic profiles of men during their first three months of androgen deprivation therapy for prostate cancer
  • Clinical Cancer Research, sous presse, 2012 (résumé)
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  Menée sur 36 patients atteints d'un cancer de la prostate, cette étude prospective analyse l'évolution de 292 métabolites après 3 mois d'un traitement anti-androgénique

  “Prospective study of changes in the metabolomic profiles of men during their first three months of androgen deprivation therapy for prostate cancer”

  • Saylor, Philip J.;Karoly, Edward D.;Smith, Matthew R.

  Purpose: Androgen deprivation therapy (ADT) for prostate cancer causes a rise in fasting insulin and adverse changes in body composition and serum lipid profile. It is unknown what other metabolic alterations are caused by ADT. In order to better characterize the metabolic effects of ADT, we measured changes in plasma metabolomic profile at baseline and after the first three months of therapy. Experimental Design: Fasting plasma samples were drawn from 36 subjects at baseline and after three months of gonadotropin releasing hormone (GnRH) agonist therapy. Extracted samples were split into equal parts for analysis on the gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry platforms. Results: Of the 292 identified metabolites, 56 changed significantly (p<0.05) from baseline to three months. Notable changes were grouped as follows: (a) Multiple steroids were lower at three months, consistent with the effect of therapy on gonadal androgen synthesis. (b) ...

  
  

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

Menée sur 43 patients atteints d'une leucémie lymphoblastique aiguë T, cette étude démontre la faisabilité d'une méthode de séquençage à haut débit pour identifier, 29 jours après le début du traitement, la présence résiduelle de la maladie

• High-Throughput Sequencing Detects Minimal Residual Disease in Acute T Lymphoblastic Leukemia
  • Science Translational Medicine, Vol. 4 (134), pp. 134ra63, 2012 (résumé)
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  Menée sur 43 patients atteints d'une leucémie lymphoblastique aiguë T, cette étude démontre la faisabilité d'une méthode de séquençage à haut débit pour identifier, 29 jours après le début du traitement, la présence résiduelle de la maladie

  “High-Throughput Sequencing Detects Minimal Residual Disease in Acute T Lymphoblastic Leukemia”

  • Wu, David;Sherwood, Anna;Fromm, Jonathan R.;Winter, Stuart S.;Dunsmore, Kimberly P.;Loh, Mignon L.;Greisman, Harvey A.;Sabath, Daniel E.;Wood, Brent L.;Robins, Harlan

  High-throughput sequencing (HTS) of lymphoid receptor genes is an emerging technology that can comprehensively assess the diversity of the immune system. Here, we applied HTS to the diagnosis of T-lineage acute lymphoblastic leukemia/lymphoma. Using 43 paired patient samples, we then assessed minimal residual disease (MRD) at day 29 after treatment. The variable regions of TCRB and TCRG were sequenced using an Illumina HiSeq platform after performance of multiplexed polymerase chain reaction, which targeted all potential V-J rearrangement combinations. Pretreatment samples were used to define clonal T cell receptor (TCR) complementarity-determining region 3 (CDR3) sequences, and paired posttreatment samples were evaluated for MRD. Abnormal T lymphoblast identification by multiparametric flow cytometry was concurrently performed for comparison. We found that TCRB and TCRG HTS not only identified clonality at diagnosis in most cases (31 of 43 for TCRB and 27 of 43 for TCRG) but also ...

  
  

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

Menée sur des échantillons de sérum prélevés sur 103 patients atteints d'un adénocarcinome colorectal, cette étude identifie des profils métaboliques associés aux différents stades de la maladie

• Serum metabolomic profile as a means to distinguish stage of colorectal cancer
  • Genome Medicine, Vol. 4 (5), pp. 42, 2012 (article en libre accès)
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  Menée sur des échantillons de sérum prélevés sur 103 patients atteints d'un adénocarcinome colorectal, cette étude identifie des profils métaboliques associés aux différents stades de la maladie

  “Serum metabolomic profile as a means to distinguish stage of colorectal cancer”

  • Farshidfar, Farshad;Weljie, Aalim;Kopciuk, Karen;Buie, W;MacLean, Anthony;Dixon, Elijah;Sutherland, Francis;Molckovsky, Andrea;Vogel, Hans;Bathe, Oliver

  BACKGROUND:Presently, colorectal cancer (CRC) is staged preoperatively by radiographic tests, and postoperatively by pathological evaluation of available surgical specimens. However, present staging methods do not accurately identify occult metastases. This has a direct effect on clinical management. Early identification of metastases isolated to the liver may enable surgical resection, whereas more disseminated disease may be best treated with palliative chemotherapy.METHODS:Sera from 103 patients with colorectal adenocarcinoma treated at the same tertiary cancer center were analyzed by proton nuclear magnetic resonance (^1H NMR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). Metabolic profiling was done using both supervised pattern recognition and orthogonal partial least squares-discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. The metabolomic profiles generated from each ...

  
  

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

Menée sur 154 patients atteints d'un adénocarcinome métastatique du pancréas et inclus dans l'essai AViTA, ainsi que 110 patients atteints d'un carcinome rénal métastatique et inclus dans l'essai AVOREN, cette étude identifie un polymorphisme à simple nucléotide du gène VEGFR1 associé à la réponse au bevacizumab

• VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials
  • The Lancet Oncology, sous presse, 2012 (résumé)
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  Menée sur 154 patients atteints d'un adénocarcinome métastatique du pancréas et inclus dans l'essai AViTA, ainsi que 110 patients atteints d'un carcinome rénal métastatique et inclus dans l'essai AVOREN, cette étude identifie un polymorphisme à simple nucléotide du gène VEGFR1 associé à la réponse au bevacizumab

  “VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials”

  • Lambrechts, Diether;Claes, Bart;Delmar, Paul;Reumers, Joke;Mazzone, Massimiliano;Yesilyurt, Betül T.;Devlieger, Roland;Verslype, Chris;Tejpar, Sabine;Wildiers, Hans;de Haas, Sanne;Carmeliet, Peter;Scherer, Stefan J.;Van Cutsem, Eric

  No biomarkers that could guide patient selection for treatment with the anti-VEGF monoclonal antibody bevacizumab have been identified. We assessed whether genetic variants in the VEGF pathway could act as biomarkers for bevacizumab treatment outcome. We investigated DNA from white patients from two phase 3 randomised studies. In AViTA, patients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine and erlotinib plus either bevacizumab or placebo. In AVOREN, patients with metastatic renal-cell carcinoma were randomly assigned to receive interferon alfa-2a plus either bevacizumab or placebo. We assessed the correlation of 138 SNPs in the VEGF pathway with progression-free survival and overall survival in a subpopulation of patients from AViTA. Significant findings were confirmed in a subpopulation of patients from AVOREN and functionally studied at the molecular level. We investigated DNA of 154 patients from AViTA, of whom 77 received bevacizumab, and ...

  
  
• Predictive value of loci in VEGF pathway genes in bevacizumab treatment
  • The Lancet Oncology, sous presse, 2012 (commentaire)
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  Menée sur 154 patients atteints d'un adénocarcinome métastatique du pancréas et inclus dans l'essai AViTA, ainsi que 110 patients atteints d'un carcinome rénal métastatique et inclus dans l'essai AVOREN, cette étude identifie un polymorphisme à simple nucléotide du gène VEGFR1 associé à la réponse au bevacizumab

  “Predictive value of loci in VEGF pathway genes in bevacizumab treatment”

  • Moroni, Mauro

  VEGF pathway genes are highly polymorphic, with multiple common single nucleotide polymorphisms (SNPs) in regulatory regions able to affect function or expression of proteins and to alter risk and prognosis of various diseases that are tightly regulated by angiogenesis. Recently, this genetic variability has been studied as a potential predictive biomarker of outcome in patients treated with bevacizumab in colorectal, breast, and ovarian cancer. All these studies described an association betwe ...

  
  

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

Menée entre 1997 et 2009 auprès de 496 femmes entre 25 et 65 ans présentant une mutation du gène BRCA1 ou BRCA2, dont 380 sans antécédent de cancer, cet essai prospectif évalue l'intérêt d'un examen annuel combinant une IRM et une mammographie pour détecter précocement un cancer du sein (57 cas)

• Long-term results of screening with magnetic resonance imaging in women with BRCA mutations
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  Menée entre 1997 et 2009 auprès de 496 femmes entre 25 et 65 ans présentant une mutation du gène BRCA1 ou BRCA2, dont 380 sans antécédent de cancer, cet essai prospectif évalue l'intérêt d'un examen annuel combinant une IRM et une mammographie pour détecter précocement un cancer du sein (57 cas)

  “Long-term results of screening with magnetic resonance imaging in women with BRCA mutations”

  • Passaperuma, K.;Warner, E.;Causer, P. A.;Hill, K. A.;Messner, S.;Wong, J. W.;Jong, R. A.;Wright, F. C.;Yaffe, M. J.;Ramsay, E. A.;Balasingham, S.;Verity, L.;Eisen, A.;Curpen, B.;Shumak, R.;Plewes, D. B.;Narod, S. A.

  Background : The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in our screening study. Methods : From 1997 to 2009, 496 women aged 25 to 65 years with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were enrolled in a prospective screening trial that included annual MRI and mammography. Results :In 1847 screening rounds, 57 cancers were identified (53 screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19% over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002 (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative sensitivities of MRI and mammography did not differ by ...

  
  

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

Menée sur une cohorte de 724 patients atteints d'un cancer de la prostate traité par prostatectomie radicale, cette étude montre une association non linéaire entre les niveaux sériques préopératoires de stéroïdes sexuels et un risque élevé de récidive

• Serum sex steroids depict a nonlinear u-shaped association with high-risk prostate cancer at radical prostatectomy
  • Clinical Cancer Research, sous presse, 2012 (résumé)
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  Menée sur une cohorte de 724 patients atteints d'un cancer de la prostate traité par prostatectomie radicale, cette étude montre une association non linéaire entre les niveaux sériques préopératoires de stéroïdes sexuels et un risque élevé de récidive

  “Serum sex steroids depict a nonlinear u-shaped association with high-risk prostate cancer at radical prostatectomy”

  • Salonia, Andrea;Abdollah, Firas;Capitanio, Umberto;Suardi, Nazareno;Briganti, Alberto;Gallina, Andrea;Colombo, Renzo;Ferrari, Matteo;Castagna, Giulia;Rigatti, Patrizio;Montorsi, Francesco

  PURPOSE. Assess the association between preoperative serum total testosterone (tT), 17betaestradiol (E2), sex hormone-binding globulin (SHBG), and tT-E2 ratio values with high-risk prostate cancer (PCa; as defined by the National Comprehensive Cancer Network practice guidelines) at radical prostatectomy (RP). METHODS. Serum E2, tT, and SHBG were dosed the day before surgery (7-11 AM) in a cohort of 724 candidates to RP. Restricted cubic spline functions tested the association between predictors (ie, model 1: age, body mass index [BMI], and serum tT, E2, and SHBG levels; Model 2: tT-E2 values instead of tT and E2 levels) and high-risk PCa. RESULTS. Low-, intermediate-, or high-risk PCa was found in 251 (34.7%), 318 (43.9%), and 155 (21.4%) patients, respectively. Patients in the high-risk class showed the lowest tT, E2, and tT-E2 ratio values (all p ≤ 0.02). At univariate analysis, only age, tT, E2, and tT-E2 ratio values were significantly associated with high-risk PCa (all p ≤ ...

  
  

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

Menée sur une cohorte de 125 patients atteints d'un cancer de la prostate, cette étude danoise montre une association entre les niveaux urinaires de la protéine EN2 avant une prostatectomie et le volume tumoral

• Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer
  • BJU International, sous presse, 2012 (résumé)
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  Menée sur une cohorte de 125 patients atteints d'un cancer de la prostate, cette étude danoise montre une association entre les niveaux urinaires de la protéine EN2 avant une prostatectomie et le volume tumoral

  “Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer”

  • Pandha, Hardev;Sorensen, Karen D.;Orntoft, Thorsten F.;Langley, Stephen;Hoyer, Soren;Borre, Michael;Morgan, Richard

  What's known on the subject? and What does the study add?There are a lot of potential prostate cancer biomarkers being evaluated. All aim to improve on the sensitivity and specificity of PSA. EN2 was recently shown by our group to have better sensitivity and specificity than PSA. EN2 is a simple ELISA test and is not dependent on other parameters, even PSA, unlike all the other current biomarkers under evaluation. To date, no marker correlates with the amount of cancer present – the present study shows this positive correlation with EN2 in men undergoing prostatectomy.The potential utility of this work is that by knowing that the level of EN2 corresponds to the amount of cancer present, irrelevant of tumour grade and number of cancer foci, we can define an EN2 level corresponding to small cancers, which can then undergo surveillance. We are conducting a further study that is aimed at determining whether the levels of EN2 in urine can indicate ‘significant’ vs ‘non-significant ...

  
  

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

Menée sur 137 patients atteints d'un cancer de la prostate diagnostiqué entre 2007 et 2009, cette étude prospective monocentrique montre qu'un faible niveau sanguin de testostérone avant le traitement est associé à des facteurs pronostiques défavorables

• Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment
  • BJU International, sous presse, 2012 (résumé)
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  Menée sur 137 patients atteints d'un cancer de la prostate diagnostiqué entre 2007 et 2009, cette étude prospective monocentrique montre qu'un faible niveau sanguin de testostérone avant le traitement est associé à des facteurs pronostiques défavorables

  “Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment”

  • García-Cruz, Eduardo;Piqueras, Marta;Huguet, Jorge;Peri, Lluis;Izquierdo, Laura;Musquera, Mireia;Franco, Agustin;Alvarez-Vijande, Ricardo;Ribal, Maria Jose;Alcaraz, Antonio

  Study Type – Prognosis (case series)Level of Evidence 4What's known on the subject? and What does the study add?Prostate growth is ruled by testosterone. Nevertheless, the paradigm that high testosterone levels induce prostate cancer development or lead to a poor prognosis in prostate cancer is not supported by evidence. A growing number of studies suggest that, on the contrary, low testosterone levels are related to poor prognosis features in prostate cancer such as higher prostate-specific antigen or higher Gleason score.Our experience shows that testosterone levels are related to risk of progression of prostate cancer – those men with lower testosterone levels are at higher risk of progression of their prostate cancer after treatment delivery. OBJECTIVES * •Low testosterone levels have been related to a higher diagnosis of prostate cancer (PCa). Hormonal levels have been related to poor prognosis factors in men with PCa, mainly after radical prostatectomy. * •Our aim was ...

  
  

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

Menée sur 643 patients atteints d'un cancer de la prostate résistant à la castration et présentant des métastases osseuses traitées par l'acide zolédronique, cette étude évalue l'association entre l'évolution des niveaux sanguins de l'antigène prostatique spécifique, les événements liés au squelette, la progression de la maladie osseuse et la survie des patients

• Prostate-Specific Antigen Kinetics and Outcomes in Patients with Bone Metastases from Castration-Resistant Prostate Cancer Treated with or Without Zoledronic Acid
  • European urology, sous presse, 2012 (résumé)
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  Menée sur 643 patients atteints d'un cancer de la prostate résistant à la castration et présentant des métastases osseuses traitées par l'acide zolédronique, cette étude évalue l'association entre l'évolution des niveaux sanguins de l'antigène prostatique spécifique, les événements liés au squelette, la progression de la maladie osseuse et la survie des patients

  “Prostate-Specific Antigen Kinetics and Outcomes in Patients with Bone Metastases from Castration-Resistant Prostate Cancer Treated with or Without Zoledronic Acid”

  • Fred, Saad;Scott, Segal;James, Eastham

  Background : Zoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker for monitoring prostate cancer patients, correlations between PSA and disease outcomes during ZOL therapy are unclear. Objective : To evaluate the relationships among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men with bone metastases from CRPC using a ZOL phase 3 trial database. Design, setting, and participants:Exploratory analyses from a phase 3 trial in men with bone metastases from CRPC (n = 643) randomized to ZOL or placebo every 3 wk. Outcome measurements and statistical analysis: PSA levels during the first 3 mo of the study were evaluated in linear and logarithmic (log) models stratified using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram. Relative risks of SREs, bone disease progression ...

  
  

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

Menée sur une cohorte américaine comportant 117 hommes et 107 femmes atteints d'un cancer du poumon non à petites cellules traité par radiothérapie définitive combinée ou non à une chimiothérapie, cette étude montre une association entre un polymorphisme à simple nucléotide du gène HSPB1 et le risque de décès

• HSPB1 Gene Polymorphisms Predict Risk of Mortality for US Patients after Radio(chemo)therapy for Non-Small Cell Lung Cancer
  • International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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  Menée sur une cohorte américaine comportant 117 hommes et 107 femmes atteints d'un cancer du poumon non à petites cellules traité par radiothérapie définitive combinée ou non à une chimiothérapie, cette étude montre une association entre un polymorphisme à simple nucléotide du gène HSPB1 et le risque de décès

  “HSPB1 Gene Polymorphisms Predict Risk of Mortality for US Patients after Radio(chemo)therapy for Non-Small Cell Lung Cancer”

  • Xu, Ting;Wei, Qingyi;Guerra, Jose Luis Lopez;Wang, Li- E.;Liu, Zhensheng;Gomez, Daniel;O'Reilly, Michael;Lin, Steven Hsesheng;Zhuang, Yan;Levy, Lawrence B.;Mohan, Radhe;Zhou, Honghao;Liao, Zhongxing

  We investigated potential associations between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall survival in US patients with non-small cell lung cancer (NSCLC). Using available genomic DNA samples from 224 patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative probability and Cox proportional hazards analyses to evaluate the effect of HSPB1 genotypes on survival. Our cohort consisted of 117 men and 107 women, mostly white (79.5%), with a median age of 70 years. The median radiation dose was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC (61%). Univariate and multivariate analyses showed that this genotype was associated with poorer survival than CG and GG genotypes (univariate hazard ratio [HR] = 1.39, 95% confidence ...

  
  

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

Menée sur 154 900 hommes et femmes participant à un programme de dépistage du cancer colorectal (âge : 55 à 74 ans ; durée médiane de suivi : 11,9 ans), cette étude évalue l'effet d'une sigmoïdoscopie flexible sur l'incidence de la maladie et la mortalité associée

• Colorectal-Cancer Incidence and Mortality with Screening Flexible Sigmoidoscopy
  • New England Journal of Medicine, sous presse, 2012 (résumé)
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  Menée sur 154 900 hommes et femmes participant à un programme de dépistage du cancer colorectal (âge : 55 à 74 ans ; durée médiane de suivi : 11,9 ans), cette étude évalue l'effet d'une sigmoïdoscopie flexible sur l'incidence de la maladie et la mortalité associée

  “Colorectal-Cancer Incidence and Mortality with Screening Flexible Sigmoidoscopy”

  • Schoen, Robert E.;Pinsky, Paul F.;Weissfeld, Joel L.;Yokochi, Lance A.;Church, Timothy;Laiyemo, Adeyinka O.;Bresalier, Robert;Andriole, Gerald L.;Buys, Saundra S.;Crawford, E. David;Fouad, Mona N.;Isaacs, Claudine;Johnson, Christine C.;Reding, Douglas J.;O'Brien, Barbara;Carrick, Danielle M.;Wright, Patrick;Riley, Thomas L.;Purdue, Mark P.;Izmirlian, Grant;Kramer, Barnett S.;Miller, Anthony B.;Gohagan, John K.;Prorok, Philip C.;Berg, Christine D.

  Background : The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. Methods : From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. Results : Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 ...

  
  
• Why You Should Care about Screening Flexible Sigmoidoscopy
  • New England Journal of Medicine, sous presse, 2012 (éditorial en libre accès)
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  Menée sur 154 900 hommes et femmes participant à un programme de dépistage du cancer colorectal (âge : 55 à 74 ans ; durée médiane de suivi : 11,9 ans), cette étude évalue l'effet d'une sigmoïdoscopie flexible sur l'incidence de la maladie et la mortalité associée

  “Why You Should Care about Screening Flexible Sigmoidoscopy”

  • Inadomi, John M.

  
  

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

A partir d'une revue de la littérature publiée entre 1966 et 2011 (12 études), cette étude évalue l'association entre une polypose adénomateuse familiale et le risque de cancer colorectal

• Risk for Colorectal Cancer in Persons With a Family History of Adenomatous Polyps
  • Annals of Internal Medicine, Vol. 156 (10), pp. 703-709, 2012 (résumé)
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  A partir d'une revue de la littérature publiée entre 1966 et 2011 (12 études), cette étude évalue l'association entre une polypose adénomateuse familiale et le risque de cancer colorectal

  “Risk for Colorectal Cancer in Persons With a Family History of Adenomatous Polyps”

  • Imperiale, Thomas F.;Ransohoff, David F.

  Background: The risk for colorectal cancer (CRC) is unclear for persons who have first-degree relatives with adenomatous polyps (adenomas).Purpose: To determine the validity of studies about this issue.Data Sources: MEDLINE and Cochrane databases from 1966 through 2011.Study Selection: Sequential review of titles, abstracts, and text from retrieved articles.Data Extraction: Study objective, study design, and numbers in study groups.Data Synthesis: Ten studies were identified that have been used to answer the question, “Does having a first-degree relative with an adenoma increase the risk for CRC?” We determined that they instead answer the question, “Does having a first-degree relative with CRC increase the risk for an adenoma?” We identified 2 additional studies that provide more relevant information. One study showed that the risk for CRC in persons who have first-degree relatives with adenomas is greater than the risk in persons who do not have first-degree relatives with ...

  
  

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

Menée sur 53 patients atteints d'un cancer de l'anus (durée médiane de suivi : 20,3 mois), cette étude évalue, par rapport à une tomographie numérique, la précision et la spécificité d'une tomographie numérique par émission de positrons dans la stadification des ganglions inguinaux et le suivi de la maladie

• Role of Positron Emission Tomography-Computed Tomography in the Management of Anal Cancer
  • International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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  Menée sur 53 patients atteints d'un cancer de l'anus (durée médiane de suivi : 20,3 mois), cette étude évalue, par rapport à une tomographie numérique, la précision et la spécificité d'une tomographie numérique par émission de positrons dans la stadification des ganglions inguinaux et le suivi de la maladie

  “Role of Positron Emission Tomography-Computed Tomography in the Management of Anal Cancer”

  • Mistrangelo, Massimiliano;Pelosi, Ettore;Bellò, Marilena;Ricardi, Umberto;Milanesi, Enrica;Cassoni, Paola;Baccega, Massimo;Filippini, Claudia;Racca, Patrizia;Lesca, Adriana;Munoz, Fernando H.;Fora, Gianluca;Skanjeti, Andrea;Cravero, Francesca;Morino, Mario

  Pre- and post-treatment staging of anal cancer are often inaccurate. The role of positron emission tomograpy-computed tomography (PET-CT) in anal cancer is yet to be defined. The aim of the study was to compare PET-CT with CT scan, sentinel node biopsy results of inguinal lymph nodes, and anal biopsy results in staging and in follow-up of anal cancer. Fifty-three consecutive patients diagnosed with anal cancer underwent PET-CT. Results were compared with computed tomography (CT), performed in 40 patients, and with sentinel node biopsy (SNB) (41 patients) at pretreatment workup. Early follow-up consisted of a digital rectal examination, an anoscopy, a PET-CT scan, and anal biopsies performed at 1 and 3 months after the end of treatment. Data sets were then compared. At pretreatment assessment, anal cancer was identified by PET-CT in 47 patients (88.7%) and by CT in 30 patients (75%). The detection rates rose to 97.9% with PET-CT and to 82.9% with CT (P=.042) when the 5 patients who ...

  
  

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

Cet article présente la mise à jour des recommandations d'un groupe d'experts américains (U.S. Preventive Services Task Force) en matière de dépistage du cancer de la prostate

• Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement
  • Annals of Internal Medicine, pp. E-459, 2012 (article en libre accès)
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  Cet article présente la mise à jour des recommandations d'un groupe d'experts américains (U.S. Preventive Services Task Force) en matière de dépistage du cancer de la prostate

  “Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement”

  • Moyer, Virginia A.

  Description: Update of the 2008 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for prostate cancer.Methods: The USPSTF reviewed new evidence on the benefits and harms of prostate-specific antigen (PSA)–based screening for prostate cancer, as well as the benefits and harms of treatment of localized prostate cancer.Recommendation: The USPSTF recommends against PSA-based screening for prostate cancer (grade D recommendation).This recommendation applies to men in the general U.S. population, regardless of age. This recommendation does not include the use of the PSA test for surveillance after diagnosis or treatment of prostate cancer; the use of the PSA test for this indication is outside the scope of the USPSTF.

  
  
• What the U.S. Preventive Services Task Force Missed in Its Prostate Cancer Screening Recommendation
  • Annals of Internal Medicine, sous presse, 2012 (commentaire en libre accès)
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  Cet article présente la mise à jour des recommandations d'un groupe d'experts américains (U.S. Preventive Services Task Force) en matière de dépistage du cancer de la prostate

  “What the U.S. Preventive Services Task Force Missed in Its Prostate Cancer Screening Recommendation”

  • Catalona, William J. ; D'Amico, Anthony V. ; Fitzgibbons, William F. ; Kosoko-Lasaki, Omofolasade ; Leslie, Stephen W. ; Lynch, Henry T. ; Moul, Judd W. ; Rendell, Marc S. ; Walsh, Patrick C.

  The U.S. Preventive Services Task Force (USPSTF), a panel that does not include urologists or cancer specialists, has just recommended against prostate-specific antigen (PSA)-based screening for prostate cancer, stating that “screening may benefit a small number of men but will result in harm to many others” (1). Recognizing that prostate cancer remains the second-leading cause of cancer deaths in men, we, an ad hoc group that includes nationally recognized experts in the surgical and radiological treatment of prostate cancer, oncologists, preventive medicine specialists, and primary care physicians, believe that the USPSTF has underestimated the benefits and overestimated the harms of prostate cancer screening. Therefore, we disagree with the USPSTF's recommendation. The USPTSF bases its recommendation, in large part, on the 2 largest published randomized clinical trials (2). The U.S. PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial randomly assigned 76 685 ...

  
  
• Prostate Cancer Screening: What We Know, Don't Know, and Believe
  • Annals of Internal Medicine, sous presse, 2012 (commentaire en libre accès)
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  Cet article présente la mise à jour des recommandations d'un groupe d'experts américains (U.S. Preventive Services Task Force) en matière de dépistage du cancer de la prostate

  “Prostate Cancer Screening: What We Know, Don't Know, and Believe”

  • Brawley, Otis W.

  Prostate cancer is a devastating illness. Approximately 28 000 American men will die of it this year (1). A method to prevent these deaths is sorely needed. For more than 20 years, many have believed that screening asymptomatic men of a certain age with serum prostate-specific antigen (PSA) is that method. Yet, every medical intervention has some harms associated with it and we must weigh those harms against potential benefits. Potential harms of PSA screening are well-documented (2), but questions surround the potential benefits: Does PSA-based screening lead to decreased morbidity and mortality? If beneficial, do the benefits outweigh the harms? After a review of the evidence about both the benefits and harms of PSA screening and treatment of localized prostate cancer, the U.S. Preventive Services Task Force (USPSTF) gave PSA screening a grade of “D” (3). This is a recommendation against PSA-based screening for men of any age. The Task Force makes D recommendations when there ...

  
  

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

A partir des données du programme britannique de dépistage du cancer colorectal portant sur 2 269 983 tests de recherche de sang occulte dans les selles et 36 460 coloscopies, cette étude analyse la qualité des coloscopies réalisées sur la période 2006-2009 et décrit les nouveaux indicateurs pris en compte pour évaluer et améliorer cette qualité

• Colonoscopy quality measures: experience from the NHS Bowel Cancer Screening Programme
  • Gut, Vol. 61 (7), pp. 1050-1057, 2012 (résumé)
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  A partir des données du programme britannique de dépistage du cancer colorectal portant sur 2 269 983 tests de recherche de sang occulte dans les selles et 36 460 coloscopies, cette étude analyse la qualité des coloscopies réalisées sur la période 2006-2009 et décrit les nouveaux indicateurs pris en compte pour évaluer et améliorer cette qualité

  “Colonoscopy quality measures: experience from the NHS Bowel Cancer Screening Programme”

  • Lee, Thomas J W;Rutter, Matthew D;Blanks, Roger G;Moss, Sue M;Goddard, Andrew F;Chilton, Andrew;Nickerson, Claire;McNally, Richard J Q;Patnick, Julietta;Rees, Colin J

  Objectives Colonoscopy is central to colorectal cancer (CRC) screening. Success of CRC screening is dependent on colonoscopy quality. The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood (FOB) testing to 60–74 year olds and colonoscopy to those with positive FOB tests. All colonoscopists in the screening programme are required to meet predetermined standards before starting screening and are subject to ongoing quality assurance. In this study, the authors examine the quality of colonoscopy in the NHS BCSP and describe new and established measures to assess and maintain quality.Design The NHS BCSP database collects detailed data on all screening colonoscopies. Prospectively collected data from the first 3 years of the programme (August 2006 to August 2009) were analysed. Colonoscopy quality indicators (adenoma detection rate (ADR), polyp detection rate, colonoscopy withdrawal time, caecal intubation rate, rectal retroversion rate, polyp retrieval ...

  
  

Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Politiques et programmes de dépistage)

A partir des données d'un essai suédois portant sur 38 589 participantes à un programme de dépistage précoce du cancer du sein (âge : 40 à 74 ans) et sur 18 582 témoins, cette étude évalue le taux de surdiagnostic associé aux mammographies (durée de suivi : 29 ans)

• Long-term incidence of breast cancer by trial arm in one county of the Swedish Two-County Trial of mammographic screening
  • Cancer, sous presse, 2012 (résumé)
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  A partir des données d'un essai suédois portant sur 38 589 participantes à un programme de dépistage précoce du cancer du sein (âge : 40 à 74 ans) et sur 18 582 témoins, cette étude évalue le taux de surdiagnostic associé aux mammographies (durée de suivi : 29 ans)

  “Long-term incidence of breast cancer by trial arm in one county of the Swedish Two-County Trial of mammographic screening”

  • Yen, Amy Ming-Fang;Duffy, Stephen W.;Chen, Tony Hsiu-Hsi;Chen, Li-Sheng;Chiu, Sherry Yueh-Hsia;Fann, Jean Ching-Yuan;Wu, Wendy Yi-Ying;Su, Chiu-Wen;Smith, Robert A.;Tabár, Lászlo

  BACKGROUND: This study estimated the excess incidence (overdiagnosis) of breast cancer associated with starting mammographic screening at an earlier age, by using data from the Dalarna County component of the Swedish Two-County Trial of breast cancer screening. METHODS: In Dalarna County, Sweden, 38,589 women aged 40 to 74 years were randomized to invitation to regular mammographic screening (active study population [ASP]) and 18,582 women to usual care (passive study population [PSP]). After 3 screening rounds (6-8 years after randomization), the PSP was invited to screening. The cumulative incidence of breast cancer was calculated in the ASP and PSP from randomization to 29 years later. In addition, cumulative incidence was calculated for invasive cancers, advanced invasive cancers (≥2 cm in maximum diameter or node-positive), and nonadvanced cancers (<2 cm and node negative). RESULTS: There was no excess of cancers in the ASP at 29 year follow-up (relative risk, 1.00; 95% ...

  
  

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

Menée en Allemagne auprès de 12 139 participants âgés de 30 à 54 ans, cette étude transversale évalue l'efficacité d'un questionnaire visant à informer, au sein d'une population bénéficiant d'une assurance maladie, les personnes ayant un risque familial et héréditaire de cancer colorectal et à améliorer la détection précoce de ce cancer

• Does a screening questionnaire for familial and hereditary colorectal cancer risk work in a health insurance population?
  • European Journal of Cancer Care, sous presse, 2012 (résumé)
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  Menée en Allemagne auprès de 12 139 participants âgés de 30 à 54 ans, cette étude transversale évalue l'efficacité d'un questionnaire visant à informer, au sein d'une population bénéficiant d'une assurance maladie, les personnes ayant un risque familial et héréditaire de cancer colorectal et à améliorer la détection précoce de ce cancer

  “Does a screening questionnaire for familial and hereditary colorectal cancer risk work in a health insurance population?”

  • Pieper, C.;Kolankowska, I.;JÖCkel, K. H.

  The aim of our study was to evaluate actual prevalence, uptake and first experiences with a questionnaire developed for early detection of colorectal cancer (CRC) in persons with familial/hereditary risk. A cross sectional study in an insurance population aged 30–54 years was conducted. Subjects with ICD-10 codes C00 to C97 and D37 to D48 were excluded. A standardised questionnaire was sent to 12 139 subjects. Three months later, subjects with a reported family history were followed by a second questionnaire. An additional telephone survey was performed to validate responses. Nineteen per cent met the inclusion criteria (mean age 45 ± 7 years, 38% men). Three hundred and seventy-three subjects (16%) were followed by a second questionnaire. Of these, 248 (66%) returned. Forty-four per cent were already aware of their increased risk of developing CRC. Awareness was associated with knowledge of CRC. One hundred subjects (41%) reported that they had informed their general practitioner ...

  
  

Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

Cet article passe en revue les travaux récents sur l'usage de modèles murins génétiquement modifés pour identifier des biomarqueurs prédictifs de la réponse thérapeutique

• Genetically Engineered Mouse Models: Closing the Gap between Preclinical Data and Trial Outcomes
  • Cancer Research, sous presse, 2012 (résumé)
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  Cet article passe en revue les travaux récents sur l'usage de modèles murins génétiquement modifés pour identifier des biomarqueurs prédictifs de la réponse thérapeutique

  “Genetically Engineered Mouse Models: Closing the Gap between Preclinical Data and Trial Outcomes”

  • Singh, Mallika;Murriel, Christopher L.;Johnson, Leisa

  The high failure rate of late-stage human clinical trials, particularly in oncology, predicates the need for improved translation of preclinical data from mouse tumor models into clinical predictions. Genetically engineered mouse models (GEMM) may fulfill this need, because they mimic spontaneous and autochthonous disease progression. Using oncogenic Kras-driven GEMMs of lung and pancreatic adenocarcinoma, we recently showed that these models can closely phenocopy human therapeutic responses to standard-of-care treatment regimens. Here we review the successful preclinical application of such GEMMs, as well as the potential for discovering predictive biomarkers and gaining mechanistic insights into clinical outcomes and drug resistance in human cancers. Cancer Res; 72(11); 1–6. ©2012 AACR.

  
  

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