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Accueil Nota Bene Cancer V2 Numéro 117 du 04 January 2012 Dépistage, diagnostic et pronostic

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Nota Bene Cancer Numéro 117 du 04 January 2012 RSS

Dépistage, diagnostic et pronostic

Découverte de technologies et de biomarqueurs

Menée in vitro et in vivo sur des modèles de glioblastome, cette étude suggère que le niveau sérique du facteur de croissance hépatocytaire pourrait servir de biomarqueur prédictif de la réponse à un traitement par inhibiteur de MET

  • Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma
    Proceedings of the National Academy of Sciences, sous presse, 2011 (article en libre accès)
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    Menée in vitro et in vivo sur des modèles de glioblastome, cette étude suggère que le niveau sérique du facteur de croissance hépatocytaire pourrait servir de biomarqueur prédictif de la réponse à un traitement par inhibiteur de MET

    “Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma”

    • Xie, Qian;Bradley, Robert;Kang, Liang;Koeman, Julie;Ascierto, Maria Libera;Worschech, Andrea;De Giorgi, Valeria;Wang, Ena;Kefene, Lisa;Su, Yanli;Essenburg, Curt;Kaufman, Dafna W.;DeKoning, Tom;Enter, Mark A.;O'Rourke, Timothy J.;Marincola, Francesco M.;Vande Woude, George F.

    Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development against several types of cancer, including glioblastoma, it is important to identify predictive markers that indicate patient subgroups suitable for such therapies. We investigated in vivo glioblastoma models characterized by hepatocyte growth factor (HGF) autocrine or paracrine activation, or by MET or EGFR amplification, for their susceptibility to MET inhibitors. HGF autocrine expression correlated with high phospho-MET levels in HGF autocrine cell lines, and these lines showed high sensitivity to MET inhibition in vivo. An HGF paracrine environment may enhance glioblastoma growth in vivo but did not indicate sensitivity to MET inhibition. EGFRvIII amplification predicted sensitivity to EGFR inhibition, but in the same tumor, increased copies of MET from gains of chromosome 7 did not result in increased MET activity and did not predict sensitivity to MET inhibitors. Thus, HGF autocrine glioblastoma ...


Mots clés : Système nerveux central; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

A partir de trois lignées cellulaires de glioblastome multiforme, cette étude évalue les performances d'une biopuce protéomique conçue pour analyser les niveaux d'une douzaine de protéines membranaires et cytoplasmiques à l'échelle d'une cellule tumorale

  • Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells
    Proceedings of the National Academy of Sciences, sous presse, 2011 (résumé)
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    A partir de trois lignées cellulaires de glioblastome multiforme, cette étude évalue les performances d'une biopuce protéomique conçue pour analyser les niveaux d'une douzaine de protéines membranaires et cytoplasmiques à l'échelle d'une cellule tumorale

    “Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells”

    • Shi, Qihui;Qin, Lidong;Wei, Wei;Geng, Feng;Fan, Rong;Shik Shin, Young;Guo, Deliang;Hood, Leroy;Mischel, Paul S.;Heath, James R.

    We describe a microchip designed to quantify the levels of a dozen cytoplasmic and membrane proteins from single cells. We use the platform to assess protein–protein interactions associated with the EGF-receptor-mediated PI3K signaling pathway. Single-cell sensitivity is achieved by isolating a defined number of cells (n = 0–5) in 2 nL volume chambers, each of which is patterned with two copies of a miniature antibody array. The cells are lysed on-chip, and the levels of released proteins are assayed using the antibody arrays. We investigate three isogenic cell lines representing the cancer glioblastoma multiforme, at the basal level, under EGF stimulation, and under erlotinib inhibition plus EGF stimulation. The measured protein abundances are consistent with previous work, and single-cell analysis uniquely reveals single-cell heterogeneity, and different types and strengths of protein–protein interactions. This platform helps provide a comprehensive picture of altered ...


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

Evaluation des technologies et des biomarqueurs

A partir de données portant sur 3 940 patients présentant des métastases cérébrales de divers types de cancer, cette étude évalue les performances d'un indicateur diagnostique pour estimer la survie des patients et choisir le traitement le plus approprié

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    A partir de données portant sur 3 940 patients présentant des métastases cérébrales de divers types de cancer, cette étude évalue les performances d'un indicateur diagnostique pour estimer la survie des patients et choisir le traitement le plus approprié

    “Summary Report on the Graded Prognostic Assessment: An Accurate and Facile Diagnosis-Specific Tool to Estimate Survival for Patients With Brain Metastases”

    • Sperduto, Paul W.;Kased, Norbert;Roberge, David;Xu, Zhiyuan;Shanley, Ryan;Luo, Xianghua;Sneed, Penny K.;Chao, Samuel T.;Weil, Robert J.;Suh, John;Bhatt, Amit;Jensen, Ashley W.;Brown, Paul D.;Shih, Helen A.;Kirkpatrick, John;Gaspar, Laurie E.;Fiveash, John B.;Chiang, Veronica;Knisely, Jonathan P.S.;Sperduto, Christina Maria;Lin, Nancy;Mehta, Minesh

    Purpose Our group has previously published the Graded Prognostic Assessment (GPA), a prognostic index for patients with brain metastases. Updates have been published with refinements to create diagnosis-specific Graded Prognostic Assessment indices. The purpose of this report is to present the updated diagnosis-specific GPA indices in a single, unified, user-friendly report to allow ease of access and use by treating physicians.Methods A multi-institutional retrospective (1985 to 2007) database of 3,940 patients with newly diagnosed brain metastases underwent univariate and multivariate analyses of prognostic factors associated with outcomes by primary site and treatment. Significant prognostic factors were used to define the diagnosis-specific GPA prognostic indices. A GPA of 4.0 correlates with the best prognosis, whereas a GPA of 0.0 corresponds with the worst prognosis.Results Significant prognostic factors varied by diagnosis. For lung cancer, prognostic factors were Karnofsky ...


Mots clés : Système nerveux central; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

A partir de données portant sur 2 936 patientes finlandaises atteintes d'un cancer du sein, cette étude compare la survie à long terme des patientes dont le cancer a été détecté par une mammographie de dépistage et la survie de celles dont le cancer a été détecté par d'autres méthodes (durée médiane de suivi : 15,4 ans)

  • Long-term prognosis of breast cancer detected by mammography screening or other methods
    Breast Cancer Research, Vol. 13 (6), pp. R134, 2011 (article en libre accès)
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    A partir de données portant sur 2 936 patientes finlandaises atteintes d'un cancer du sein, cette étude compare la survie à long terme des patientes dont le cancer a été détecté par une mammographie de dépistage et la survie de celles dont le cancer a été détecté par d'autres méthodes (durée médiane de suivi : 15,4 ans)

    “Long-term prognosis of breast cancer detected by mammography screening or other methods”

    • Lehtimaki, Tiina;Lundin, Mikael;Linder, Nina;Sihto, Harri;Holli, Kaija;Turpeenniemi-Hujanen, Taina;Kataja, Vesa;Isola, Jorma;Joensuu, Heikki;Lundin, Johan

    INTRODUCTION:Previous studies on breast cancer have shown that patients whose tumors are detected by mammography screening have a more favorable survival. However, little is known about the long-term prognostic impact of screen-detection. The purpose of the current study was to compare breast cancer-specific long-term survival between patients whose tumors were detected in mammography screening and those detected by other methods.METHODS:Breast cancer patients diagnosed within five specified geographical areas in Finland in 1991-92 were identified (n=2,936). Detailed clinical, treatment and outcome data as well as tissue samples were collected. Women with in situ carcinoma, distant metastases at the primary diagnosis and women who were not operated were excluded. Main analyses were made with exclusions of patients with other malignancy or contralateral breast cancer followed by to sensitivity analyses with different exclusion criterias. Median follow-up time was 15.4 years. Univariate ...


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

Cet article passe en revue les travaux récents sur la classification des cancers du sein et l'analyse des plus importantes voies de signalisation

  • Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways
    Cancer treatment reviews, sous presse, 2011 (résumé)
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    Cet article passe en revue les travaux récents sur la classification des cancers du sein et l'analyse des plus importantes voies de signalisation

    “Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways”

    • Eroles, Pilar;Bosch, Ana;Alejandro Pérez-Fidalgo, J.;Lluch, Ana

    The last decade has brought a breakthrough in the knowledge of the biology of breast cancer. The technological development, and in particular the high throughput technologies, have allowed researchers to inquire more deeply into the nature of the disease through the comparative study of large numbers of samples. The classification of breast cancer by traditional parameters has been joined by rankings based on gene expression. Among the most popular platforms are MammaPrint®, Oncotype DX® the wound-response model, the rate of two genes model, the genomic grade index and the intrinsic subtype model. The latter one provides the amplest biological information and allows for the classification of breast cancer into six intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, normal breast and claudin-low. These new classifications are not yet fully applicable to clinical practice not only because they have not been standardized, but also because they entail a substantial ...


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

A partir de données portant sur 289 patientes atteintes d'un cancer du sein, cette étude compare le statut des récepteurs ER, PgR et HER2 entre les tumeurs primitives et les tumeurs récidivantes

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    A partir de données portant sur 289 patientes atteintes d'un cancer du sein, cette étude compare le statut des récepteurs ER, PgR et HER2 entre les tumeurs primitives et les tumeurs récidivantes

    “Tissue confirmation of disease recurrence in breast cancer patients: Pooled analysis of multi-centre, multi-disciplinary prospective studies”

    • Amir, Eitan;Clemons, Mark;Purdie, Colin A.;Miller, Naomi;Quinlan, Phil;Geddie, William;Coleman, Robert E.;Freedman, Orit C.;Jordan, Lee B.;Thompson, Alastair M.

    Treatment decisions in recurrent breast cancer are usually based on the estrogen (ER), progesterone (PgR) and HER2 receptor status of the primary tumour. Retrospective studies suggest that discordance between receptor expression of primary and recurrent breast cancer exists. A pooled analysis of individual patient data from two large prospective studies comprising biopsy of recurrent lesions obtained from consenting patients was undertaken. Tissue was analyzed for ER, PgR by immunohistochemistry and HER2 by FISH. Receptor status of recurrent disease was compared with that of the primary tumour. Recruiting clinicians assessed whether or not receptor discordance affected subsequent systemic treatment. Two hundred and eighty-nine patients underwent biopsy. Recurrent biopsy specimens were obtained from locoregional recurrence in 48.1% and from distant metastases in 51.9%. Distant sites included skin/soft tissue (25.0%), bone/bone marrow (19.2%) and liver (15.8%). Benign disease or second ...


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

Menée sur des échantillons tumoraux prélevés sur 145 patients atteints d'un rhabdomyosarcome, cette étude évalue l'association entre l'expression du gène ALK, fréquemment muté dans cette maladie, et la survie des patients

  • Anaplastic Lymphoma Kinase Aberrations in Rhabdomyosarcoma: Clinical and Prognostic Implications
    Journal of Clinical Oncology, sous presse, 2011 (résumé)
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    Menée sur des échantillons tumoraux prélevés sur 145 patients atteints d'un rhabdomyosarcome, cette étude évalue l'association entre l'expression du gène ALK, fréquemment muté dans cette maladie, et la survie des patients

    “Anaplastic Lymphoma Kinase Aberrations in Rhabdomyosarcoma: Clinical and Prognostic Implications”

    • van Gaal, J. Carlijn;Flucke, Uta E.;Roeffen, Melissa H.S.;de Bont, Eveline S.J.M.;Sleijfer, Stefan;Mavinkurve-Groothuis, Annelies M.C.;Suurmeijer, Albert J.H.;van der Graaf, Winette T.A.;Versleijen-Jonkers, Yvonne M.H.

    Purpose The aim of this study is to investigate anaplastic lymphoma kinase (ALK) protein expression and underlying genetic aberrations in rhabdomyosarcoma (RMS), with special attention to clinical and prognostic implications.Patients and Methods A total of 189 paraffin-embedded RMS tumor specimens from 145 patients were collected on tissue microarray. ALK protein expression was evaluated by immunohistochemistry. ALK gene (2p23) copy number and translocations were determined by in situ hybridization. cDNA sequencing of the receptor tyrosine kinase domain of the ALK gene was assessed in 43 samples.Results Strong cytoplasmic ALK protein expression was more frequently observed in alveolar RMS (ARMS) than in embryonal RMS (ERMS) (81% v 32%, respectively; P < .001). ALK gene copy number gain was detected in the vast majority of ARMS (88%), compared with 52% of ERMS (P < .001). ALK copy number correlated with protein expression in primary tumors (n = 107). We identified one point mutation ...


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

Menée sur 168 patientes atteintes d'un cancer de l'ovaire, cette étude analyse les différences dans l'expression de diverses protéines associées à la réponse thérapeutique entre les tumeurs primitives et les tumeurs récidivantes

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    Menée sur 168 patientes atteintes d'un cancer de l'ovaire, cette étude analyse les différences dans l'expression de diverses protéines associées à la réponse thérapeutique entre les tumeurs primitives et les tumeurs récidivantes

    “Treatment-related protein biomarker expression differs between primary and recurrent ovarian carcinomas”

    • Zajchowski, Deborah A;Karlan, Beth Y.;Shawver, Laura K

    The molecular characteristics of recurrent ovarian cancers following chemotherapy treatment have been poorly characterized. Such knowledge could impact salvage therapy selection. Since 2008, we have profiled 168 patients' ovarian cancers to determine the expression of proteins that may predict chemotherapy response or are targets for drugs that are in clinical trials for ovarian cancer treatment. Expression of EGFR, HER2, VEGF, ER, c-Met, IGF1R, Ki67, COX2, PGP/MDR1, BCRP, MRP1, ERCC1, MGMT, TS, RRM1, TOPO1, TOP2A, and SPARC was measured by immunohistochemical analyses at Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories. Our univariate analysis of 56 primary and 50 recurrent tumors from patients with advanced stage ovarian serous carcinoma revealed that PGP and ERCC1 were significantly up-regulated in recurrent lesions (p<0.05). To determine whether these or any of the other markers were differentially expressed in specimens obtained from the same individual at ...


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

Cet article passe en revue les travaux récents sur le développement de biomarqueurs prédictifs de la réponse à un traitement anti-angiogénique chez les patientes atteintes d'un cancer de l'ovaire

  • Biomarkers in the development of anti-angiogenic therapies for ovarian cancer
    Cancer treatment reviews, sous presse, 2011 (résumé)
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    Cet article passe en revue les travaux récents sur le développement de biomarqueurs prédictifs de la réponse à un traitement anti-angiogénique chez les patientes atteintes d'un cancer de l'ovaire

    “Biomarkers in the development of anti-angiogenic therapies for ovarian cancer”

    • Raja, Fharat A.;Hook, Jane M.;Ledermann, Jonathan A.

    The treatment of ovarian cancer remains challenging as the majority of patients will relapse and die from their disease despite successful first-line treatment. New treatment strategies are needed and recently there has been an explosion of new agents being tested in ovarian cancer. Most of these are directed against molecularly defined pathways and a significant proportion target angiogenesis, an important process in the growth of ovarian cancer. We review the role of angiogenesis in the pathophysiology of ovarian cancer and discuss the development of the most promising anti-angiogenic drugs in this disease, including the first large phase III trials with bevacizumab which have demonstrated a disease-modifying role in ovarian cancer. Other studies with this drug and other inhibitors of the angiogenic pathways are underway in the first-line and recurrent disease settings. The financial cost of these agents, increased toxicity and requirement for prolonged therapy necessitates the ...


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

Essais de technologies et de biomarqueurs dans un contexte clinique

Menée sur une cohorte de 396 patients atteints d'un cancer localisé ou avancé de la prostate (durée médiane de suivi : 3,7 ans), cette étude évalue l'association entre le niveau sérique de facteurs de croissance apparentés à l'insuline (IGF-I, IGF-II, IGFBP-2 and IGFBP-3) et le risque de décès

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    Menée sur une cohorte de 396 patients atteints d'un cancer localisé ou avancé de la prostate (durée médiane de suivi : 3,7 ans), cette étude évalue l'association entre le niveau sérique de facteurs de croissance apparentés à l'insuline (IGF-I, IGF-II, IGFBP-2 and IGFBP-3) et le risque de décès

    “Serum insulin-like growth factors and mortality in localised and advanced clinically detected prostate cancer”

    • Rowlands, Mari-Anne;Holly, Jeff;Hamdy, Freddie;Phillips, Joshua;Goodwin, Louise;Marsden, Gemma;Gunnell, David;Donovan, Jenny;Neal, David;Martin, Richard

    Context Many studies have reported associations of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with prostate cancer development, but none have investigated their association with fatal progression of prostate cancer. Objective We investigated associations of circulating IGF-I, IGF-II, IGFBP-2 and IGFBP-3 with all-cause and prostate cancer mortality in men with clinically identified prostate cancer, stratified by whether localised (stage T1 or T2) or advanced (T3, T4, N1 or M1) at diagnosis. Design, setting and participants UK hospital-based cohort study of 396 men with prostate cancer, diagnosed between 1990 and 2008, with mean follow-up of 3.7 years. Main outcome measures All-cause and prostate cancer–specific mortality. Results In men with advanced cancer, there was some evidence that IGF-I was positively associated (HR 1.20; 95% CI: 0.96, 1.49; p = 0.11) and IGFBP-3 was inversely associated (HR 0.84; 95% CI: 0.70, 1.01; p = 0.07) with all-cause mortality ...


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

Menée aux Etats-Unis et en Australie à partir d'échantillons de carcinome de l'ovaire, cette étude multicentrique (173 cas) montre une association entre le niveau d'expression de la protéine TLE3 (Transducin-like enhancer protein 3) et la réponse à une chimiothérapie par taxane

  • TLE3 expression is associated with sensitivity to taxane treatment in ovarian carcinoma
    Cancer Epidemiology Biomarkers & Prevention, sous presse, 2011 (résumé)
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    Menée aux Etats-Unis et en Australie à partir d'échantillons de carcinome de l'ovaire, cette étude multicentrique (173 cas) montre une association entre le niveau d'expression de la protéine TLE3 (Transducin-like enhancer protein 3) et la réponse à une chimiothérapie par taxane

    “TLE3 expression is associated with sensitivity to taxane treatment in ovarian carcinoma”

    • Samimi, Goli;Ring, Brian Z;Ross, Doug T;Seitz, Robert S;Sutherland, Robert L;O'Brien, Philippa M;Hacker, Neville;Huh, Warner K

    Background: We have previously demonstrated that TLE3 is associated with outcome specifically in taxane-treated breast cancer patients and not in patients treated with anthracycline-based regimens without a taxane. The purpose of this study was to assess the association between TLE3 expression and recurrence in ovarian carcinoma patients treated with a taxane containing regimen as opposed to those treated with a platinum-based agent alone. Methods: We performed immunohistochemical staining of TLE3 in 2 series of ovarian cancer specimens from the University of Alabama at Birmingham, USA and the Royal Hospital for Women, Sydney, Australia. Local and distant recurrences within the first five years of follow-up were analyzed using Kaplan Meier, Cox proportional hazard and multivariate analysis to assess an association between TLE3 expression and response to therapy. Results: TLE3 was expressed in approximately 30% of tumors and expression was associated with a favorable outcome only in ...


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

Menée à partir des données de l'essai multicentrique AML96 incluant 586 patients atteints de leucémie myéloïde aiguë et âgés de 15 à 60 ans, cette étude analyse l'association entre des variables biologiques et la survie des patients après une rémission complète et évalue la valeur pronostique d'un indice pouvant aider les médecins à orienter les patients vers le traitement le mieux adapté

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    Menée à partir des données de l'essai multicentrique AML96 incluant 586 patients atteints de leucémie myéloïde aiguë et âgés de 15 à 60 ans, cette étude analyse l'association entre des variables biologiques et la survie des patients après une rémission complète et évalue la valeur pronostique d'un indice pouvant aider les médecins à orienter les patients vers le traitement le mieux adapté

    “Prediction of post-remission survival in acute myeloid leukaemia: a post-hoc analysis of the AML96 trial”

    • Pfirrmann, Markus;Ehninger, Gerhard;Thiede, Christian;Bornhäuser, Martin;Kramer, Michael;Röllig, Christoph;Hasford, Joerg;Schaich, Markus

    The optimum post-remission treatment (PRT) in acute myeloid leukaemia (AML) is still a matter of debate. Consolidation treatments include chemotherapy with high-dose cytarabine, or allogeneic or autologous haemopoietic stem cell transplantation (HSCT). In a post-hoc analysis of the AML96 trial (NCT00180115), our aim was to differentiate groups of patients according to the treatments that would provide them optimum benefit. In the multicentre AML96 trial, 586 patients (aged 15?60 years) with AML?excluding those with t(8;21)?who were in complete remission after double induction treatment were consolidated with allogeneic HSCT, autologous HSCT, or chemotherapy containing high-dose cytarabine in a priority-based and risk-adapted manner. We assessed the association between potentially prognostic variables and overall survival after complete remission by use of a stratified Cox regression analysis. With the significant variables of the resulting model, we developed a PRT score in 452 ...


  • Renaissance of autologous stem cell transplantation for AML?
    The Lancet Oncology, sous presse, 2011 (commentaire)
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    Menée à partir des données de l'essai multicentrique AML96 incluant 586 patients atteints de leucémie myéloïde aiguë et âgés de 15 à 60 ans, cette étude analyse l'association entre des variables biologiques et la survie des patients après une rémission complète et évalue la valeur pronostique d'un indice pouvant aider les médecins à orienter les patients vers le traitement le mieux adapté

    “Renaissance of autologous stem cell transplantation for AML?”

    • Ferrara, Felicetto


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

Menée sur 824 patients atteints d'une leucémie myéloïde aiguë et présentant des anomalies cytogénétiques, cette étude compare la valeur pronostique d'un caryotype complexe (présence de plus de 3 anomalies) et d'une monosomie

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    Menée sur 824 patients atteints d'une leucémie myéloïde aiguë et présentant des anomalies cytogénétiques, cette étude compare la valeur pronostique d'un caryotype complexe (présence de plus de 3 anomalies) et d'une monosomie

    “Prognostic value of "monosomal karyotype" in comparison to "complex aberrant karyotype" in acute myeloid leukemia: study on 824 cases with aberrant karyotype”

    • Haferlach, Claudia;Alpermann, Tamara;Schnittger, Susanne;Kern, Wolfgang;Chromik, Jörg;Schmid, Christoph;Pielken, Hermann Josef;Kreuzer, Karl-Anton;Höffkes, Heinz-Gert;Haferlach, Torsten

    In acute myeloid leukemia (AML) the subset with complex karyotype (CK) is traditionally regarded as the worst prognostic group. However, ≥3, ≥4 or ≥5 abnormalities have been variably used for its definition. Recently, "monosomal karyotype" (MSK) was suggested to indicate an even inferior outcome. We tested which definition fits best to identify the most unfavorable subgroup. After excluding patients with t(15;17)/PML-RARA, t(8;21)/RUNX1-RUNX1T1, inv(16)/t(16;16)/CBFB-MYH11 and normal karyotype 824 AML patients with cytogenetic abnormalities were analyzed. Patients with MSK or CK defined as ≥3, ≥4 or ≥5 abnormalities showed an inferior OS compared to the respective remaining patients not fulfilling these criteria (for all p<0.001). Hazard ratios were 1.93, 1.68, 1.94, and 1.92. CK≥4 as a single parameter identified the largest proportion of patients with very poor risk. However, combining CK≥4 and MSK detected an even larger number of patients with very unfavorable ...


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

Menée sur 74 patients soumis à une surveillance coloscopique, cette étude évalue l'association entre le nombre de foyers de cryptes aberrantes détectés au niveau du côlon distal lors de la première coloscopie et le risque de néoplasie colorectale

  • Aberrant crypt foci as predictors of colorectal neoplasia on repeat colonoscopy
    Cancer Causes and Control, sous presse, 2011 (résumé)
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    Menée sur 74 patients soumis à une surveillance coloscopique, cette étude évalue l'association entre le nombre de foyers de cryptes aberrantes détectés au niveau du côlon distal lors de la première coloscopie et le risque de néoplasie colorectale

    “Aberrant crypt foci as predictors of colorectal neoplasia on repeat colonoscopy”

    • Anderson, Joseph;Swede, Helen;Rustagi, Tarun;Protiva, Petr;Pleau, Devon;Brenner, Bruce;Rajan, Thiruchandurai;Heinen, Christopher;Levine, Joel;Rosenberg, Daniel

    Objective To estimate the risk for colorectal neoplasia detected on repeat colonoscopy in relation to aberrant crypt foci (ACF) frequency reported during the previous baseline examination. Methods From July 2003 until December 2008, patients had a colonoscopy with an ACF study using a magnifying colonoscope. The distal 20 cm section of colon was sprayed with Methylene Blue to ascertain the ACF frequency, the independent variable. Patients were categorized into low and high ACF count using the median as the cut point. Data collected from consenting patients included age, gender, height, weight, ethnicity, smoking history, family history of colorectal cancer (CRC), and personal history of colorectal neoplasia. A follow-up colonoscopy was performed at an interval as dictated by clinical surveillance guidelines. The main outcome was surveillance detected advanced colorectal neoplasia (SDAN) detected on repeat colonoscopy. Logistic Regression was used to calculate risk of SDAN on repeat ...


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

Menée à partir d'échantillons sanguins prélevés sur 658 patients atteints d'un cancer (251 cancers du sein, 210 cancers du poumon, 145 lymphomes, 52 cancers du côlon), cette étude en population norvégienne évalue l'association entre les niveaux sériques de la 25-hydroxyvitamine D et la survie des patients

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    Menée à partir d'échantillons sanguins prélevés sur 658 patients atteints d'un cancer (251 cancers du sein, 210 cancers du poumon, 145 lymphomes, 52 cancers du côlon), cette étude en population norvégienne évalue l'association entre les niveaux sériques de la 25-hydroxyvitamine D et la survie des patients

    “Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: a population-based study”

    • Tretli, Steinar;Schwartz, Gary;Torjesen, Peter;Robsahm, Trude

    Purpose We investigated the association between serum levels of 25-hydroxyvitamin D (25-OHD) and risk of death in Norwegian cancer patients. Methods The study population was 658 patients with cancers of the breast ( n = 251), colon ( n = 52), lung ( n = 210), and lymphoma ( n = 145), obtained from JANUS, a population-based serum bank in Norway. Serum samples were collected within 90 days of cancer diagnosis and were analyzed for 25-OHD. Patients were diagnosed during 1984–2004 and were followed for death throughout 2008. We used Cox regression models to assess the relationship between serum 25-OHD and risk of death. Results Three hundred and ninety-nine patients died during follow-up, of whom 343 (86%) died from cancer. Adjusted for sex, age at diagnosis, and season of blood sampling, patients with 25-OHD levels below 46 nmol/L at diagnosis experienced shorter survival. Compared to patients in the lowest quartile of serum 25-OHD, the risk of cancer death among patients in the ...


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

Menée sur 203 patients susceptibles de présenter des lésions pulmonaires périphériques, cette étude prospective randomisée compare l'impact de deux techniques de biopsie transbronchique guidée par échographie endobronchique (l'une utilisant un bronchoscope mince avec guidage fluoroscopique et l'autre utilisant un bronchoscope muni d'une gaine de guidage) sur la qualité des échantillons prélevés et la performance du diagnostic

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    Menée sur 203 patients susceptibles de présenter des lésions pulmonaires périphériques, cette étude prospective randomisée compare l'impact de deux techniques de biopsie transbronchique guidée par échographie endobronchique (l'une utilisant un bronchoscope mince avec guidage fluoroscopique et l'autre utilisant un bronchoscope muni d'une gaine de guidage) sur la qualité des échantillons prélevés et la performance du diagnostic

    “Randomized Study of Endobronchial Ultrasound-Guided Transbronchial Biopsy: Thin Bronchoscopic Method versus Guide Sheath Method”

    • Oki, Masahide;Saka, Hideo;Kitagawa, Chiyoe;Kogure, Yoshihito;Murata, Naohiko;Adachi, Takashi;Ando, Masahiko

    Introduction: In endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB), techniques using a thin bronchoscope or a guide sheath have been proposed for accurate biopsy instrument reinsertion into the bronchial route indicated by a radial ultrasonic probe. The purpose of this study was to compare the diagnostic yields of these techniques for peripheral pulmonary lesions. Methods: Patients with suspected peripheral pulmonary lesions were included in this prospective, randomized, noninferiority study and assigned to undergo EBUS-TBB under fluoroscopic guidance using a prototype 3.4-mm thin bronchoscope or a 4.0-mm bronchoscope with a guide sheath. Results: A total of 205 patients were enrolled and randomized, of whom 203 patients (101 thin bronchoscopic method; 102 guide sheath method) were included in the analysis. Diagnostic histologic specimens were obtained in 65% (41% for benign and 75% for malignant lesions) of the thin bronchoscopy group and 62% (25% for benign and 71% ...


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

Politiques et programmes de dépistage

Ces articles offrent divers points de vue sur le projet de recommandations, rédigées par un groupe d'experts américains, en matière de dépistage du cancer de la prostate

  • Making the Call
    JAMA: The Journal of the American Medical Association, Vol. 306 (24), pp. 2649-2650, 2011 (commentaire)
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    Ces articles offrent divers points de vue sur le projet de recommandations, rédigées par un groupe d'experts américains, en matière de dépistage du cancer de la prostate

    “Making the Call”

    • Welch, H. Gilbert

    A recommendation against PSA screening? I’ve been raising questions about the value of cancer screening for more than a decade, yet I’ve never recommended against it. But then again, I’ve never recommended for screening either. I guess that's why I’m not a member of the US Preventive Services Task Force. As you can probably tell, I am a fence-sitter (and, by the end of this essay, maybe even a flip-flopper). While I believe that media campaigns, advocacy groups, and physicians have systematically exaggerated the benefits of cancer screening and have downplayed—or, worse, ignored—its harms, I also believe that both benefits and harms exist. And no matter how well researchers can quantify this trade-off (and there is much room for improvement here), the metrics are different: small changes in cancer-specific mortality vs a boatload of hassle factors and fear, some unnecessary treatment, some resulting complications, and even a very …


  • Grading the New US Preventive Services Task Force Prostate Cancer Screening Recommendation
    JAMA: The Journal of the American Medical Association, Vol. 306 (24), pp. 2715-2716, 2011 (commentaire)
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    Ces articles offrent divers points de vue sur le projet de recommandations, rédigées par un groupe d'experts américains, en matière de dépistage du cancer de la prostate

    “Grading the New US Preventive Services Task Force Prostate Cancer Screening Recommendation”

    • Volk, Robert J. ; Wolf, Andrew M. D.

    On October 11, 2011, the US Preventive Services Task Force (USPSTF) issued for public comment a draft recommendation statement regarding screening for prostate cancer. The public comment period is a new step taken by the USPSTF prior to finalizing its recommendation statements to help make its recommendations clearer and more useful to primary care providers. In taking this step, the task force signaled its intention to change its 2008 recommendation from a grade I statement (the current evidence is insufficient to assess the balance of the benefits and harms of the service) to a grade D recommendation—“The US Preventive Services Task Force . . . recommends against prostate-specific antigen (PSA)-based screening for prostate cancer.” Following an updated review of the evidence, the USPSTF concluded that there is moderate certainty that the harms of PSA-based screening for prostate cancer outweigh the benefits. The reaction from the media to the impending change has been swift, ...


  • Missing the Mark on Prostate-Specific Antigen Screening
    JAMA: The Journal of the American Medical Association, Vol. 306 (24), pp. 2719-2720, 2011 (commentaire)
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    Ces articles offrent divers points de vue sur le projet de recommandations, rédigées par un groupe d'experts américains, en matière de dépistage du cancer de la prostate

    “Missing the Mark on Prostate-Specific Antigen Screening”

    • Miller, David C. ; Hollenbeck, Brent K.

    The US Preventive Services Task Force recently issued a draft recommendation against prostate-specific antigen (PSA) screening for prostate cancer. After performing a rigorous review of the relevant empirical literature, the task force concluded with “moderate certainty” that the harms of PSA-based detection (eg, biopsy-related complications) and early intervention (eg, incontinence, erectile dysfunction) exceed the potential benefits. For this reason, the task force now proposes discouraging PSA screening among men who are free of symptoms suspicious for prostate cancer. Most clinicians are aware that PSA is an imperfect tool for the early detection of prostate cancer. First, rather than being focused on patients most likely to benefit from early detection, the use of PSA as a screening test is often undiscerning.2 Second, PSA-based screening can be inconclusive. As a consequence, for some patients this process can lead to a cycle of repeated venipuncture and biopsy, as well as ...


  • Prostate Cancer Screening—Time to Abandon One-Size-Fits-All Approach?
    JAMA: The Journal of the American Medical Association, Vol. 306 (24), pp. 2717-2718, 2011 (commentaire)
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    Ces articles offrent divers points de vue sur le projet de recommandations, rédigées par un groupe d'experts américains, en matière de dépistage du cancer de la prostate

    “Prostate Cancer Screening—Time to Abandon One-Size-Fits-All Approach?”

    • Kim, Jeri ; Davis, John W.

    The new US Preventive Services Task Force draft recommendations discourage use of prostate-specific antigen (PSA) screening among asymptomatic men, regardless of age, race, or family medical history. This one-size-fits-all recommendation derives from the overdiagnosis and overtreatment of many patients with PSA-screened asymptomatic prostate cancer; it cites a “statistically insignificant 0.06% absolute reduction in prostate cancer–specific deaths for men aged 50 to 74 years”1 after a median of 9 years in the European Randomized Study of Screening for Prostate Cancer. But is the current evidence sufficient to discourage PSA screening in asymptomatic men and ultimately remove PSA screening from optional testing if Medicare or third-party payers adopt the task force's recommendation? Overdiagnosing and overtreating prostate cancer are major concerns. However, eliminating PSA-based screening is premature in the face of the lengthy natural history of the disease, consequences of ...


  • Prostate Cancer Screening—The Evidence, the Recommendations, and the Clinical Implications
    JAMA: The Journal of the American Medical Association, Vol. 306 (24), pp. 2721-2722, 2011 (commentaire)
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    Ces articles offrent divers points de vue sur le projet de recommandations, rédigées par un groupe d'experts américains, en matière de dépistage du cancer de la prostate

    “Prostate Cancer Screening—The Evidence, the Recommendations, and the Clinical Implications”

    • Chou, Roger ; LeFevre, Michael L.

    On October 11, 2011, the US Preventive Services Task Force (USPSTF) released its draft recommendation on prostate cancer screening. In it, the USPSTF recommended for the first time against prostate cancer screening for men of all ages (a grade “D” recommendation). Predictably, this was met with considerable controversy. The mission of the USPSTF is to improve the health of all persons in the United States by making evidence-based recommendations about clinical preventive services. Each USPSTF recommendation is based on a systematic review of the evidence.1 Before making a recommendation about a preventive service, the task force requires that the evidence be sufficient to estimate with at least moderate certainty the balance of benefits relative to harms.2 In this case, across the population of screened men, the USPSTF determined that benefits of prostate-specific antigen (PSA)–based screening for prostate cancer were outweighed by harms. As of 2010, the USPSTF process …


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

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