Dépistage, diagnostic et pronostic

Menée sur 7 patients atteints d'un cancer de la prostate métastatique et résistant à la castration, cette étude évalue la faisabilité d'une technique permettant d'isoler les cellules tumorales circulant dans le sang et de soumettre ces cellules à une analyse génomique

• Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer
  • BMC Cancer, Vol. 12 (1), pp. 78, 2012 (article en libre accès)
  Détails

  Fermer

  Menée sur 7 patients atteints d'un cancer de la prostate métastatique et résistant à la castration, cette étude évalue la faisabilité d'une technique permettant d'isoler les cellules tumorales circulant dans le sang et de soumettre ces cellules à une analyse génomique

  “Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer”

  • Magbanua, Mark Jesus;Sosa, Eduardo;Scott, Janet;Simko, Jeff;Collins, Colin;Pinkel, Dan;Ryan, Charles;Park, John

  BACKGROUND:The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment.METHODS:We developed a novel approach to isolate CTCs away from hematopoietic cells with high purity, enabling genomic analysis of these cells. The isolation protocol involves immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). To evaluate the feasibility of isolation of CTCs by IE/FACS and downstream genomic profiling, we conducted a pilot study in patients with metastatic castration resistant prostate cancer (CRPC). Twenty (20) sequential CRPC patients were assayed using CellSearchTM. Twelve (12) patients positive for CTCs were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate CTCs. Genomic DNA of CTCs was ...

  
  

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

Menée sur des cellules leucémiques, cette étude évalue les capacités d'une biopuce à détecter des cellules tumorales circulantes

• Accurate Detection of Carcinoma Cells by Use of a Cell Microarray Chip
  • PLoS ONE, Vol. 7 (3), pp. e32370, 2012 (article en libre accès)
  Détails

  Fermer

  Menée sur des cellules leucémiques, cette étude évalue les capacités d'une biopuce à détecter des cellules tumorales circulantes

  “Accurate Detection of Carcinoma Cells by Use of a Cell Microarray Chip”

  • Yamamura, Shohei;Yatsushiro, Shouki;Yamaguchi, Yuka;Abe, Kaori;Shinohara, Yasuo;Tamiya, Eiichi;Baba, Yoshinobu;Kataoka, Masatoshi

  Background: Accurate detection and analysis of circulating tumor cells plays an important role in the diagnosis and treatment of metastatic cancer treatment. Methods and Findings: A cell microarray chip was used to detect spiked carcinoma cells among leukocytes. The chip, with 20,944 microchambers (105 µm width and 50 µm depth), was made from polystyrene; and the formation of monolayers of leukocytes in the microchambers was observed. Cultured human T lymphoblastoid leukemia (CCRF-CEM) cells were used to examine the potential of the cell microarray chip for the detection of spiked carcinoma cells. A T lymphoblastoid leukemia suspension was dispersed on the chip surface, followed by 15 min standing to allow the leukocytes to settle down into the microchambers. Approximately 29 leukocytes were found in each microchamber when about 600,000 leukocytes in total were dispersed onto a cell microarray chip. Similarly, when leukocytes isolated from human whole blood were used, approximately ...

  
  

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

Menée sur 44 patients atteints d'un cancer de la vessie sans infiltration musculaire (durée de suivi : 24 mois), cette étude évalue l'intérêt de détecter des cellules tumorales circulantes pour identifier les patients à haut risque de récidive

• Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a CellSearch analysis
  • Annals of Oncology, sous presse, 2012 (résumé)
  Détails

  Fermer

  Menée sur 44 patients atteints d'un cancer de la vessie sans infiltration musculaire (durée de suivi : 24 mois), cette étude évalue l'intérêt de détecter des cellules tumorales circulantes pour identifier les patients à haut risque de récidive

  “Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a CellSearch analysis”

  • Gazzaniga, P.;Gradilone, A.;de Berardinis, E.;Busetto, G. M.;Raimondi, C.;Gandini, O.;Nicolazzo, C.;Petracca, A.;Vincenzi, B.;Farcomeni, A.;Gentile, V.;Cortesi, E.;Frati, L.

  Background: Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC).Patients and methods: Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration.Results: CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P < 0.001). Median time to progression was not reached, ...

  
  

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

Menée sur 257 patientes atteintes d'un cancer du sein, cette étude évalue l'association entre les niveaux des protéines cMET et phospho-cMET et la survie des patientes en fonction du sous-type de cancer

• cMET and phospho-cMET protein levels in breast cancers and survival outcomes
  • Clinical Cancer Research, sous presse, 2012 (résumé)
  Détails

  Fermer

  Menée sur 257 patientes atteintes d'un cancer du sein, cette étude évalue l'association entre les niveaux des protéines cMET et phospho-cMET et la survie des patientes en fonction du sous-type de cancer

  “cMET and phospho-cMET protein levels in breast cancers and survival outcomes”

  • Raghav, Kanwal P. S.;Wang, Wenting;Liu, Shuying;Chavez-MacGregor, Mariana;Meng, Xiaolong;Hortobagyi, Gabriel N.;Mills, Gordon B.;Meric-Bernstam, Funda;Blumenschein, George R;Gonzalez-Angulo, Ana M

  Purpose: To evaluate cMET and phospho-cMET (p-cMET) levels in breast cancer subtypes and its impact on survival outcomes. Experimental Design: We measured protein levels of cMET and p-cMET in 257 breast cancers using reverse phase protein array. Regression tree method and Martingale residual plots were applied to find best cutoff point for high and low levels. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and overall (OS) survival. Cox proportional hazards models were fit to determine associations of cMET/p-cMET with outcomes after adjustment for other characteristics. Results: Median age was 51years. There were 140 (54.5%) hormone receptor (HR)-positive, 53 (20.6%) HER2-positive and 64 (24.9%) triple-negative tumors. Using selected cutoffs, 181 (70.4%) and 123 (47.9%) cancers had high levels of cMET and p-cMET, respectively. There were no significant differences in mean expression of cMET (P less than 0.128) and p-cMET (P less than 0.088) by breast cancer ...

  
  

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

A partir de 17 études, cette méta-analyse compare la précision d'une biopsie à l'aiguille et d'une biopsie chirurgicale dans la détermination du statut des récepteurs ER, PgR et HER2

• Accuracy of estrogen receptor, progesterone receptor, and HER2 status between core needle and open excision biopsy in breast cancer: a meta-analysis
  • Breast Cancer Research and Treatment, sous presse, 2012 (résumé)
  Détails

  Fermer

  A partir de 17 études, cette méta-analyse compare la précision d'une biopsie à l'aiguille et d'une biopsie chirurgicale dans la détermination du statut des récepteurs ER, PgR et HER2

  “Accuracy of estrogen receptor, progesterone receptor, and HER2 status between core needle and open excision biopsy in breast cancer: a meta-analysis”

  • Chen, Xiaosong;Yuan, Ying;Gu, Zhaoxiang;Shen, Kunwei

  Accurate determination of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2) status was very important in selecting breast cancer treatment. Discordance of ER, PR, and HER2 status between core needle biopsy (CNB) and open excision biopsy (OEB) varied among reported studies. We performed a meta-analysis to compare the accuracy of CNB with that of OEB for ER, PgR, and HER2 status detection in breast cancer. Medical subject heading (MeSH) terms (Breast Neoplasm) and key words (biopsy OR mammotome) AND (incision OR excision OR surgery) AND (estrogen OR progesterone OR HER2 OR hormone). Patients with HER2 immunohistochemical 3+ or fluorescence in situ hybridization positive were classified into HER2[b] group. A total of 27 studies were eligible in this study. Aggregate positive ER and PgR rate was 80.0 and 69.5% for CNB; and 77.7 and 66.2% for OEB, respectively. The HER2 positive rate difference between CNB and OEB was only 0.2%. The ...

  
  

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

Cet article passe en revue les perspectives offertes par l'identification d'anomalies épigénétiques pour le développement de biomarqueurs d'un cancer de la prostate

• Epigenetic Biomarkers in Prostate Cancer: Current and Future Uses
  • Cancer Letters, sous presse, 2012 (résumé)
  Détails

  Fermer

  Cet article passe en revue les perspectives offertes par l'identification d'anomalies épigénétiques pour le développement de biomarqueurs d'un cancer de la prostate

  “Epigenetic Biomarkers in Prostate Cancer: Current and Future Uses”

  • Chiam, Karen;Ricciardelli, Carmela;Bianco-Miotto, Tina

  Epigenome alterations are characteristic of nearly all human malignancies and include changes in DNA methylation, histone modifications and microRNAs (miRNAs). However, what induces these epigenetic alterations in cancer is largely unknown and their mechanistic role in prostate tumorigenesis is just beginning to be evaluated. Identification of the epigenetic modifications involved in the development and progression of prostate cancer will not only identify novel therapeutic targets but also prognostic and diagnostic markers. This review will focus on the use of epigenetic modifications as biomarkers for prostate cancer.

  
  

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

Menée sur 30 patients et 20 témoins sains, cette étude évalue l'intérêt de mesurer les niveaux sériques de plusieurs micro-ARNs pour la détection précoce d'un cancer du poumon non à petites cellules

• Serum microRNA Biomarkers for Detection of Non-Small Cell Lung Cancer
  • PLoS ONE, Vol. 7 (2), pp. e32307, 2012 (article en libre accès)
  Détails

  Fermer

  Menée sur 30 patients et 20 témoins sains, cette étude évalue l'intérêt de mesurer les niveaux sériques de plusieurs micro-ARNs pour la détection précoce d'un cancer du poumon non à petites cellules

  “Serum microRNA Biomarkers for Detection of Non-Small Cell Lung Cancer”

  • Hennessey, Patrick T.;Sanford, Tiffany;Choudhary, Ashish;Mydlarz, Wojciech W.;Brown, David;Adai, Alex Tamas;Ochs, Michael F.;Ahrendt, Steven A.;Mambo, Elizabeth;Califano, Joseph A.

  Non small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality world-wide and the majority of cases are diagnosed at late stages of disease. There is currently no cost-effective screening test for NSCLC, and the development of such a test is a public health imperative. Recent studies have suggested that chest computed tomography screening of patients at high risk of lung cancer can increase survival from disease, however, the cost effectiveness of such screening has not been established. In this Phase I/II biomarker study we examined the feasibility of using serum miRNA as biomarkers of NSCLC using RT-qPCR to examine the expression of 180 miRNAs in sera from 30 treatment naive NSCLC patients and 20 healthy controls. Receiver operating characteristic curves (ROC) and area under the curve were used to identify differentially expressed miRNA pairs that could distinguish NSCLC from healthy controls. Selected miRNA candidates were further validated in sera from an ...

  
  

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

Menée sur deux cohortes de 113 et 110 patientes atteintes d'un cancer séreux de l'ovaire de haut grade, cette étude évalue l'association entre le comptage absolu des lymphocytes deux ans avant le diagnostic et la survie des patientes

• Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes
  • Journal of Translational Medicine, Vol. 10 (1), pp. 33, 2012 (article en libre accès)
  Détails

  Fermer

  Menée sur deux cohortes de 113 et 110 patientes atteintes d'un cancer séreux de l'ovaire de haut grade, cette étude évalue l'association entre le comptage absolu des lymphocytes deux ans avant le diagnostic et la survie des patientes

  “Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes”

  • Milne, Katy;Alexander, Cheryl;Webb, John;Sun, Winnie;Dillon, Kristy;Kalloger, Steve;Gilks, C. Blake;Clarke, Blaise;Kobel, Martin;Nelson, Brad

  BACKGROUND:The immune system strongly influences outcome in patients with ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. However, the mechanistic relationships between ALC, TIL and prognosis are poorly understood. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival.METHODS:ALC values were collected from patient records [greater than or equal to] 2 years before, during or after primary treatment for high-grade serous ovarian cancer (HGSC). Lymphocyte subsets were assessed in peripheral blood by flow cytometry. CD8+ and CD20+ TIL were assessed by immunohistochemistry.RESULTS:Overall, patients had normal ALC values two or more years prior to diagnosis of HGSC. These values were not predictive of disease severity or survival upon ...

  
  

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

Menée sur 498 patients atteints d'un cancer avancé de la tête et du cou de stade III ou IV, cette étude évalue, du point de vue de la survie globale, l'association entre les niveaux d'expression plasmatique du facteur de croissance des hépatocytes et de l'interleukine 8 et la réponse à une chimioradiothérapie avec ou sans tirapazamine

• Prognostic and Predictive Significance of Plasma HGF and IL-8 in a Phase III Trial of Chemoradiation with or without Tirapazamine in Locoregionally Advanced Head and Neck Cancer
  • Clinical Cancer Research, sous presse, 2012 (résumé)
  Détails

  Fermer

  Menée sur 498 patients atteints d'un cancer avancé de la tête et du cou de stade III ou IV, cette étude évalue, du point de vue de la survie globale, l'association entre les niveaux d'expression plasmatique du facteur de croissance des hépatocytes et de l'interleukine 8 et la réponse à une chimioradiothérapie avec ou sans tirapazamine

  “Prognostic and Predictive Significance of Plasma HGF and IL-8 in a Phase III Trial of Chemoradiation with or without Tirapazamine in Locoregionally Advanced Head and Neck Cancer”

  • Le, Quynh-Thu;Fisher, Richard;Oliner, Kelly S.;Young, Richard J.;Cao, Hongbin;Kong, Christina;Graves, Edward;Hicks, Rodney J.;McArthur, Grant A.;Peters, Lester;O’Sullivan, Brian;Giaccia, Amato;Rischin, Danny

  Purpose: Hepatocyte growth factor (HGF) is a hypoxia-induced secreted protein that binds to cMet and regulates interleukin (IL)-8 expression. We evaluated the role of circulating HGF and IL-8 as prognostic and predictive factors for efficacy of tirapazamine (TPZ), a hypoxic cell cytotoxin.Experimental Design: Patients with stages III to IV head and neck cancer were randomized to receive radiotherapy with cisplatin (CIS) or CIS plus TPZ (TPZ/CIS). Eligibility for the substudy included plasma sample availability for HGF and IL-8 assay by ELISA and no major radiation deviations (N = 498). Analyses included adjustment for major prognostic factors. p16INK4A staining (human papillomavirus surrogate) was carried out on available tumors. Thirty-nine patients had hypoxia imaging with 18F-fluoroazomycin arabinoside (18FAZA)–positron emission tomography.Results: Elevated IL-8 level was associated with worse overall survival (OS) irrespective of treatment. There was an interaction between HGF ...

  
  

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

Menée sur 286 patientes présentant une tumeur trophoblastique gestationnelle à faible risque et traitées par méthotrexate, cette étude évalue l'association entre l'indice de pulsatilité des artères utérines et la résistance au traitement

• Uterine artery pulsatility index: a predictor of methotrexate resistance in gestational trophoblastic neoplasia
  • British Journal of Cancer, sous presse, 2012 (résumé)
  Détails

  Fermer

  Menée sur 286 patientes présentant une tumeur trophoblastique gestationnelle à faible risque et traitées par méthotrexate, cette étude évalue l'association entre l'indice de pulsatilité des artères utérines et la résistance au traitement

  “Uterine artery pulsatility index: a predictor of methotrexate resistance in gestational trophoblastic neoplasia”

  • Agarwal, R.;Harding, V.;Short, D.;Fisher, R. A.;Sebire, N. J.;Harvey, R.;Patel, D.;Savage, P. M.;Lim, A. K. P.;Seckl, M. J.

  background : Neo-angiogenesis is a hallmark of cancer. The aim of this study was to test the hypothesis, in a prospective patient cohort, that in low-risk gestational trophoblastic neoplasia (LR-GTN) the uterine artery pulsatility index (UAPI), a measure of tumour vascularity, can predict resistance to methotrexate chemotherapy (MTX-R). Methods : 286 LR-GTN patients (Charing Cross Hospital (CXH) score 0–8, or FIGO score 0–6) were treated with methotrexate between January 2008 and June 2011 at CXH. During staging investigations, patients underwent a Doppler ultrasound to assess the UAPI. Results : 239 patients were assessable for both UAPI and MTX-R. The median UAPI was lower (higher vascularity) in MTX-R compared with MTX-sensitive patients (0.8 vs 1.4, P<0.0001). In multivariate logistic regression, UAPIless than or equal to1 predicted MTX-R, independent of both CXH and FIGO scores. The risk of MTX-R in patients with a FIGO score of 6 and UAPIless than or equal to1 was 100% vs ...

  
  

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

Menée à partir d'échantillons sanguins prélevés sur 640 patientes atteintes d'un cancer invasif du sein et sur 741 témoins, cette étude évalue l'association entre le niveau de méthylation dans les globules blancs de deux loci du gène ATM et le risque de développer la maladie

• Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast cancer risk
  • Cancer Research, sous presse, 2012 (résumé)
  Détails

  Fermer

  Menée à partir d'échantillons sanguins prélevés sur 640 patientes atteintes d'un cancer invasif du sein et sur 741 témoins, cette étude évalue l'association entre le niveau de méthylation dans les globules blancs de deux loci du gène ATM et le risque de développer la maladie

  “Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast cancer risk”

  • Brennan, Kevin;Garcias-Closas, Montserrat;Orr, Nick;Fletcher, Olivia;Jones, Michael;Ashworth, Alan;Swerdlow, Anthony;Thorne, Heather;Riboli, Elio;Vineis, Paolo;Dorronsoro, Miren;Clavel-Chapelon, Francoise;Panico, Salvatore;Onland-Moret, N Charlotte;Trichopoulos, Dimitrios;Kaaks, Rudolph;Khaw, Kay-Tee;Brown, Robert;Flanagan, James M

  Few studies have evaluated the association between DNA methylation in white blood cells (WBC) and the risk of breast cancer. The evaluation of WBC DNA methylation as a biomarker of cancer risk is of particular importance as peripheral blood is often available in prospective cohorts and easier to obtain than tumor or normal tissues. Here, we used pre-diagnostic blood samples from three studies to analyze WBC DNA methylation of two ATM intragenic loci (ATMmvp2a and ATMmvp2b) and genome-wide DNA methylation in LINE1 repetitive elements. Samples were from a case-control study derived from a cohort of high-risk breast cancer families (KConFab) and nested case-control studies in two prospective cohorts: Breakthrough Generations Study (BGS) and European Prospective Investigation into Cancer and Nutrition (EPIC). Bisulphite pyrosequencing was used to quantify methylation from 640 incident cases of invasive breast cancer and 741 controls. Quintile analyses for ATMmvp2a showed an increased risk ...

  
  

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

A partir d'échantillons tumoraux prélevés sur 471 patients atteints d'un adénocarcinome du pancréas et ayant subi une résection, cette étude de cohorte multicentrique évalue l'association entre le niveau d'expression tumorale des gènes CXCR4 et SMAD4, le risque de récidive de la maladie et la réponse à une chimiothérapie adjuvante

• Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma
  • Annals of Oncology, sous presse, 2012 (résumé)
  Détails

  Fermer

  A partir d'échantillons tumoraux prélevés sur 471 patients atteints d'un adénocarcinome du pancréas et ayant subi une résection, cette étude de cohorte multicentrique évalue l'association entre le niveau d'expression tumorale des gènes CXCR4 et SMAD4, le risque de récidive de la maladie et la réponse à une chimiothérapie adjuvante

  “Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma”

  • Bachet, J. B.;Maréchal, R.;Demetter, P.;Bonnetain, F.;Couvelard, A.;Svrcek, M.;Bardier-Dupas, A.;Hammel, P.;Sauvanet, A.;Louvet, C.;Paye, F.;Rougier, P.;Penna, C.;Vaillant, J. C.;André, T.;Closset, J.;Salmon, I.;Emile, J. F.;Van Laethem, J. L.

  Background: Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients.Patients and methods: A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1.Results: High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for ...

  
  

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

Menée sur 619 patients pédiatriques atteints de leucémie myéloïde aiguë, cette étude prospective évalue l'association entre le niveau d'expression tumorale de la protéine CD33, les caractéristiques de la maladie et la réponse à un traitement par gemtuzumab ozogamicine

• Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML
  • Blood, sous presse, 2012 (résumé)
  Détails

  Fermer

  Menée sur 619 patients pédiatriques atteints de leucémie myéloïde aiguë, cette étude prospective évalue l'association entre le niveau d'expression tumorale de la protéine CD33, les caractéristiques de la maladie et la réponse à un traitement par gemtuzumab ozogamicine

  “Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML”

  • Pollard, Jessica A.;Alonzo, Todd A.;Loken, Michael;Gerbing, Robert B.;Ho, Phoenix A.;Bernstein, Irwin D.;Raimondi, Susana C.;Hirsch, Betsy;Franklin, Janet;Walter, Roland B.;Gamis, Alan;Meshinchi, Soheil

  CD33 is expressed on the majority of acute myeloid leukemia (AML) leukemic blasts and is the target for gemtuzumab ozogamicin (GO), a toxin-conjugated anti-CD33 monoclonal antibody. CD33 mean fluorescent intensity (MFI) of leukemic blasts was prospectively quantified in 619 de novo pediatric AML patients enrolled on Children's Oncology Group GO-containing clinical trials and correlated with disease characteristics and clinical outcome. CD33 expression varied over 2-log fold; a median MFI of 129 (range 3-1550.07) was observed. Patients were divided into 4 quartiles (Q1-4) based on expression and disease characteristics and clinical response defined across quartiles. High CD33 expression was associated with high-risk FLT3/ITD mutations (P<0.001) and inversely associated with low-risk disease (P<0.001). CR rates were similar but patients in Q4 had significantly lower OS (57%+/-16% versus 77%+/- 7%, P= 0.002) and DFS from CR (44% +/- 16% versus 62% +/- 8%, P= 0.022). In a multivariate ...

  
  

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

Menée sur 446 patients présentant une cirrhose classée A ou B selon l'indice de CHILD, cette étude évalue l'efficacité d'un programme de surveillance incluant une échographie et / ou un dosage sanguin de l'alpha-fœtoprotéine pour détecter précocement un carcinome hépatocellulaire

• Effectiveness of Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis
  • Cancer Epidemiology Biomarkers & Prevention, sous presse, 2012 (résumé)
  Détails

  Fermer

  Menée sur 446 patients présentant une cirrhose classée A ou B selon l'indice de CHILD, cette étude évalue l'efficacité d'un programme de surveillance incluant une échographie et / ou un dosage sanguin de l'alpha-fœtoprotéine pour détecter précocement un carcinome hépatocellulaire

  “Effectiveness of Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis”

  • Singal, Amit G.;Conjeevaram, Hari S.;Volk, Michael L.;Fu, Sherry;Fontana, Robert J.;Askari, Fred;Su, Grace L.;Lok, Anna S.;Marrero, Jorge A.

  Background: Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis, but the effectiveness of a surveillance program in clinical practice has yet to be established. Aims: To evaluate the effectiveness of a surveillance program with ultrasound and alpha fetoprotein (AFP) to detect early HCC. Methods: 446 patients with Child A/B cirrhosis were prospectively enrolled between 1/04-9/06 and followed until 7/10. HCC surveillance using ultrasound and AFP was performed per the treating hepatologist, though the standard was every 6-12 months. HCC was diagnosed using AASLD guidelines and early HCC defined by BCLC staging. Performance characteristics were determined for surveillance using AFP, ultrasound, or the combination. Results: After a median follow-up of 3.5 years, 41 patients developed HCC, of whom 30 (73.2%) had early HCC. The annual incidence of HCC was 2.8%, with cumulative 3- and 5-year incidence rates of 5.7% and 9.1% respectively. Surveillance ...

  
  

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

Mené sur 491 patients atteints d'un carcinome hépatocellulaire de stade avancé, cet essai de phase III évalue l'association entre les niveaux plasmatiques de 10 biomarqueurs impliqués dans la pathogenèse de la maladie (parmi lesquels l'angiopoïétine 2 et le facteur de croissance endothélial vasculaire), la réponse à un traitement par sorafénib et la survie des patients

• Plasma Biomarkers as Predictors of Outcome in Patients with Advanced Hepatocellular Carcinoma
  • Clinical Cancer Research, sous presse, 2012 (résumé)
  Détails

  Fermer

  Mené sur 491 patients atteints d'un carcinome hépatocellulaire de stade avancé, cet essai de phase III évalue l'association entre les niveaux plasmatiques de 10 biomarqueurs impliqués dans la pathogenèse de la maladie (parmi lesquels l'angiopoïétine 2 et le facteur de croissance endothélial vasculaire), la réponse à un traitement par sorafénib et la survie des patients

  “Plasma Biomarkers as Predictors of Outcome in Patients with Advanced Hepatocellular Carcinoma”

  • Llovet, Josep M;Pena, Carol;Lathia, Chetan;Shan, Minghua;Meinhardt, Gerold;Bruix, Jordi

  Background & Aims: Validated biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma (HCC). One of the objectives of the phase III, randomized, controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy. Methods: In SHARP, 602 patients with advanced HCC were randomized to receive either oral sorafenib 400 mg bid po or matching placebo daily on a continuous basis. Ten plasma biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at baseline and in 305 after 12 weeks of treatment. The candidate biomarkers were analyzed to identify correlates of prognosis or predictors of response to sorafenib. Results: In both the entire patient population and the placebo cohort, baseline angiopoietin 2 (Ang2) and vascular endothelial growth factor (VEGF) concentrations independently predicted survival. Clinical ...

  
  

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

Menée sur 1 230 femmes suédoises atteintes d'un cancer invasif du col de l'utérus diagnostiqué entre 1999 et 2001 (durée moyenne de suivi : 8,5 ans), cette étude prospective évalue l'intérêt de détecter la maladie avant la survenue de symptômes pour améliorer leur espérance de vie

• Screening and cervical cancer cure: population based cohort study
  • BMJ, Vol. 344, 2012 (résumé)
  Détails

  Fermer

  Menée sur 1 230 femmes suédoises atteintes d'un cancer invasif du col de l'utérus diagnostiqué entre 1999 et 2001 (durée moyenne de suivi : 8,5 ans), cette étude prospective évalue l'intérêt de détecter la maladie avant la survenue de symptômes pour améliorer leur espérance de vie

  “Screening and cervical cancer cure: population based cohort study”

  • Bengt Andrae;Therese M-L Andersson;Paul C Lambert;Levent Kemetli;Lena Silfverdal;Björn Strander;Walter Ryd;Joakim Dillner;Sven Törnberg;Pär Sparén

  Objective : To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. Design Nationwide population based cohort study. Setting Sweden : Participants All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. Main outcome measures Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age, histopathological type, and FIGO (International Federation of Gynecology and Obstetrics) stage. Results In the screening ages, the cure proportion for women with screen detected invasive cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was 66% (62% to 70%), a statistically significant difference in cure of 26% (16% to 36%). Among symptomatic women, the cure proportion was significantly higher for those who had been screened according to recommendations (interval ...

  
  
• Effect of screening on deaths from cervical cancer in Sweden
  • BMJ, Vol. 344, 2012 (éditorial)
  Détails

  Fermer

  Menée sur 1 230 femmes suédoises atteintes d'un cancer invasif du col de l'utérus diagnostiqué entre 1999 et 2001 (durée moyenne de suivi : 8,5 ans), cette étude prospective évalue l'intérêt de détecter la maladie avant la survenue de symptômes pour améliorer leur espérance de vie

  “Effect of screening on deaths from cervical cancer in Sweden”

  • M Arbyn ; E Weiderpass ; R Capocaccia

  
  

Mots clés : Col de l'utérus; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Cette étude évalue la faisabilité d'une technique à haut débit pour l'identification de mutations associées à une thérapie ciblée dans le traitement d'un mélanome

• A high throughput panel for identifying clinically-relevant mutation profiles in melanoma
  • Molecular Cancer Therapeutics, sous presse, 2012 (résumé)
  Détails

  Fermer

  Cette étude évalue la faisabilité d'une technique à haut débit pour l'identification de mutations associées à une thérapie ciblée dans le traitement d'un mélanome

  “A high throughput panel for identifying clinically-relevant mutation profiles in melanoma”

  • Dutton-Regester, Ken;Irwin, Darryl;Hunt, Priscilla;Aoude, Lauren;Tembe, Varsha;Pupo, Gulietta M;Lanagan, Cathy;Carter, Candace D;O'Connor, Linda;O'Rourke, Michael;Scolyer, Richard A;Mann, Graham J;Schmidt, Christopher W;Herington, Adrian;Hayward, Nicholas K

  Success with molecular-based targeted drugs in the treatment of cancers has ignited extensive research efforts within the field of personalised therapeutics. However, successful application of such therapies is dependent on the presence or absence of mutations within the patient's tumor that can confer clinical efficacy or drug resistance. Building on these findings, we developed a high throughput mutation panel for the identification of frequently occurring and clinically-relevant mutations in melanoma. An extensive literature search and interrogation of the Catalogue of Somatic Mutations in Cancer (COSMIC) database identified over 1000 melanoma mutations. Applying a filtering strategy to focus on mutations amenable to the development of targeted drugs, we initially screened 120 different known mutations in 271 samples using the Sequenom MassARRAY® system. A total of 252 mutations were detected in 17 genes. The highest frequency mutations occurred in BRAF (n=154, 57%), NRAS (n=55, ...

  
  

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

Cet article présente les recommandations d'une société savante américaine en matière de dépistage du cancer colorectal

• Screening for Colorectal Cancer: A Guidance Statement From the American College of Physicians
  • Annals of Internal Medicine, Vol. 156 (5), pp. 378-386, 2012 (article en libre accès)
  Détails

  Fermer

  Cet article présente les recommandations d'une société savante américaine en matière de dépistage du cancer colorectal

  “Screening for Colorectal Cancer: A Guidance Statement From the American College of Physicians”

  • Qaseem, Amir;Denberg, Thomas D.;Hopkins, Robert H.;Humphrey, Linda L.;Levine, Joel;Sweet, Donna E.;Shekelle, Paul

  Description: Colorectal cancer is the second leading cause of cancer-related deaths for men and women in the United States. The American College of Physicians (ACP) developed this guidance statement for clinicians by assessing the current guidelines developed by other organizations on screening for colorectal cancer. When multiple guidelines are available on a topic or when existing guidelines conflict, ACP believes that it is more valuable to provide clinicians with a rigorous review of the available guidelines rather than develop a new guideline on the same topic.Methods: The authors searched the National Guideline Clearinghouse to identify guidelines developed in the United States. Four guidelines met the inclusion criteria: a joint guideline developed by the American Cancer Society, the U.S. Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology and individual guidelines developed by the Institute for Clinical Systems Improvement, the U.S. Preventive ...

  
  

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

Menée auprès de 415 médecins généralistes américains, cette étude évalue leur degré de compréhension des bénéfices apportés par un programme de dépistage du cancer

• Do Physicians Understand Cancer Screening Statistics? A National Survey of Primary Care Physicians in the United States
  • Annals of Internal Medicine, Vol. 156 (5), pp. 340-349, 2012 (résumé)
  Détails

  Fermer

  Menée auprès de 415 médecins généralistes américains, cette étude évalue leur degré de compréhension des bénéfices apportés par un programme de dépistage du cancer

  “Do Physicians Understand Cancer Screening Statistics? A National Survey of Primary Care Physicians in the United States”

  • Wegwarth, Odette;Schwartz, Lisa M.;Woloshin, Steven;Gaissmaier, Wolfgang;Gigerenzer, Gerd

  Reader Survey: Test your knowledge of cancer screening statisticsBackground: Unlike reduced mortality rates, improved survival rates and increased early detection do not prove that cancer screening tests save lives. Nevertheless, these 2 statistics are often used to promote screening.Objective: To learn whether primary care physicians understand which statistics provide evidence about whether screening saves lives.Design: Parallel-group, randomized trial (randomization controlled for order effect only), conducted by Internet survey. (ClinicalTrials.gov registration number: NCT00981019)Setting: National sample of U.S. primary care physicians from a research panel maintained by Harris Interactive (79% cooperation rate).Participants: 297 physicians who practiced both inpatient and outpatient medicine were surveyed in 2010, and 115 physicians who practiced exclusively outpatient medicine were surveyed in 2011.Intervention: Physicians received scenarios about the effect of 2 hypothetical ...

  
  
• What We Don't Know Can Hurt Our Patients: Physician Innumeracy and Overuse of Screening Tests
  • Annals of Internal Medicine, Vol. 156 (5), pp. 392-393, 2012 (éditorial)
  Détails

  Fermer

  Menée auprès de 415 médecins généralistes américains, cette étude évalue leur degré de compréhension des bénéfices apportés par un programme de dépistage du cancer

  “What We Don't Know Can Hurt Our Patients: Physician Innumeracy and Overuse of Screening Tests”

  • Moyer, Virginia A.

  Patients, the public, and even health professionals enthusiastically support screening for disease, especially screening for cancer. Unfortunately, whether many members of these groups fully understand the benefits and risks that would allow an informed decision is not clear. This has not, however, dampened the enthusiasm for screening. A decade ago, Schwartz and colleagues (1) found that 87% of a national sample of adults believed that routine cancer screening is almost always a good idea and 74% said that early detection saves lives most or all of the time—to the point that more than one third considered an 80-year-old person who declined screening to be irresponsible. As chair of the U.S. Preventive Services Task Force when the draft recommendation on prostate-specific antigen (PSA) screening was released, I find my e-mail inbox replete with personal stories from men who are convinced that PSA screening saved their lives. However, even for mammography screening for breast cancer, ...

  
  

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