Dépistage, diagnostic et pronostic

Découverte de technologies et de biomarqueurs

Menée sur 98 patientes atteintes d'un cancer non métastatique du sein, cette étude évalue la faisabilité de mesurer des biomarqueurs dans les cellules tumorales circulantes pour orienter le choix thérapeutique et assurer le suivi du traitement

Biomarkers Characterization of Circulating Tumour Cells in Breast Cancer Patients
• Breast Cancer Research, Vol. 14 (3), pp. R71, 2012 (article en libre accès)

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Menée sur 98 patientes atteintes d'un cancer non métastatique du sein, cette étude évalue la faisabilité de mesurer des biomarqueurs dans les cellules tumorales circulantes pour orienter le choix thérapeutique et assurer le suivi du traitement

“Biomarkers Characterization of Circulating Tumour Cells in Breast Cancer Patients”

• Nadal, Rosa;Fernandez, Ana;Sanchez-Rovira, Pedro;Salido, Marta;Rodriguez, Maria;Garcia-Puche, Jose;Macia, Marta;Coromines, Josep;Delgado-Rodriguez, Miguel;Gonzalez, Lucas;Albanell, Joan;Fernandez, Monica;Sole, Francesc;Lorente, Jose;Serrano, M. Jose

INTRODUCTION:Increasing evidence supports that the detection of circulating tumour cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumour and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease.METHODS:98 nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTCs detection through immunocytochemical methods. Estrogen receptor, Progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by Fluorescence in situ Hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate with clinical-pathological characteristics.RESULTS:Baseline detection rate was 46.9% ...

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

Menée sur 67 patients atteints d'un cancer colorectal métastatique, cette étude rétrospective évalue l'association entre la présence de mutations des gènes KRAS, BRAF, PIK3CA et la réponse au cetuximab

Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: a single center study
• Journal of Translational Medicine, Vol. 10 (1), pp. 87, 2012 (article en libre accès)

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Menée sur 67 patients atteints d'un cancer colorectal métastatique, cette étude rétrospective évalue l'association entre la présence de mutations des gènes KRAS, BRAF, PIK3CA et la réponse au cetuximab

“Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: a single center study”

• Ulivi, Paola;Capelli, Laura;Valgiusti, Martina;Zoli, Wainer;Scarpi, Emanuela;Chiadini, Elisa;Rosetti, Paola;Bravaccini, Sara;Calistri, Daniele;Saragoni, Luca;Casadei Gardini, Andrea;Ragazzini, Angela;Frassineti, Giovanni Luca;Amadori, Dino;Passardi, Alessandro

BACKGROUND:KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of KRAS wild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding KRAS WT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status of KRAS, BRAF, PIK3CA and PTEN expression in mCRC patients treated with a cetuximab-based regimen.METHODS:67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were analyzed by direct sequencing, PIK3CA was evaluated by pyrosequencing and PTEN expression by immunohistochemistry.RESULTS:BRAF and PIK3CA mutations were independently associated with PFS (p= 0.006 and p=0.028, respectively) and OS ...

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

Evaluation des technologies et des biomarqueurs

Menée sur 906 patientes canadiennes ayant reçu un diagnostic de cancer du sein sans envahissement ganglionnaire entre 2004 et 2007, cette étude évalue l'impact d'une double lecture anatomopathologique sur la prise en charge des patientes

Impact of Routine Pathology Review on Treatment for Node-Negative Breast Cancer
• Journal of Clinical Oncology, sous presse, 2012 (résumé)

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Menée sur 906 patientes canadiennes ayant reçu un diagnostic de cancer du sein sans envahissement ganglionnaire entre 2004 et 2007, cette étude évalue l'impact d'une double lecture anatomopathologique sur la prise en charge des patientes

“Impact of Routine Pathology Review on Treatment for Node-Negative Breast Cancer”

• Kennecke, Hagen F.;Speers, Caroline H.;Ennis, Catherine A.;Gelmon, Karen;Olivotto, Ivo A.;Hayes, Malcolm

Purpose Routine secondary pathology review influences diagnosis and treatment among patients diagnosed with breast cancer. The impact of review on patients with node-negative breast cancer and the nature of the pathology elements leading to management changes are not well described.Methods Patients with node-negative, invasive, or in situ breast cancer and evaluable nodes referred to the British Columbia Cancer Agency during two time periods between 2004 and 2007 were included. Pathologists with expertise in breast cancer reviewed the original reports and slides. Biomarker testing was not routinely repeated. Medical record review was conducted to determine whether original pathology was changed and whether recommended therapy was affected.Results Among 906 eligible patients, 405 (45%) received a pathology review. Univariate comparisons revealed that reviewed patients were younger (P < .001) and more likely to have close margins (P < .001), whereas other characteristics were similar. A ...

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

Essais de technologies et de biomarqueurs dans un contexte clinique

A partir de l'analyse par RT-PCR de 465 échantillons de carcinome rhinopharyngé et de 18 échantillons de rhinopharyngite, cette étude rétrospective chinoise évalue l'association entre l'expression de 41 micro-ARNs et la survie des patients

Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis
• The Lancet Oncology, sous presse, 2012 (résumé)

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A partir de l'analyse par RT-PCR de 465 échantillons de carcinome rhinopharyngé et de 18 échantillons de rhinopharyngite, cette étude rétrospective chinoise évalue l'association entre l'expression de 41 micro-ARNs et la survie des patients

“Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis”

• Liu, Na;Chen, Nian-Yong;Cui, Rui-Xue;Li, Wen-Fei;Li, Yan;Wei, Rong-Rong;Zhang, Mei-Yin;Sun, Ying;Huang, Bi-Jun;Chen, Mo;He, Qing-Mei;Jiang, Ning;Chen, Lei;Cho, William C. S.;Yun, Jing-Ping;Zeng, Jing;Liu, Li-Zhi;Li, Li;Guo, Ying;Wang, Hui-Yun;Ma, Jun

MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma. We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature ...
Personalised medicine in nasopharyngeal cancer
• The Lancet Oncology, sous presse, 2012 (commentaire)

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A partir de l'analyse par RT-PCR de 465 échantillons de carcinome rhinopharyngé et de 18 échantillons de rhinopharyngite, cette étude rétrospective chinoise évalue l'association entre l'expression de 41 micro-ARNs et la survie des patients

“Personalised medicine in nasopharyngeal cancer”

• Toh, Toh Han Chong Han Chong ; Ha, Ha Tam Cam Tam Cam ; Wee, Joseph

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

Menée en Chine sur 1 533 patients atteints d'un carcinome rhinopharyngé, cette étude prospective de cohorte évalue l'association entre des habitudes de vie avant traitement et la survie des patients

Pretreatment Lifestyle Behaviors as Survival Predictors for Patients with Nasopharyngeal Carcinoma
• PLoS ONE, Vol. 7 (5), pp. e36515, 2012 (article en libre accès)

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Menée en Chine sur 1 533 patients atteints d'un carcinome rhinopharyngé, cette étude prospective de cohorte évalue l'association entre des habitudes de vie avant traitement et la survie des patients

“Pretreatment Lifestyle Behaviors as Survival Predictors for Patients with Nasopharyngeal Carcinoma”

• Shen, Guo-Ping;Xu, Feng-Hua;He, Fen;Ruan, Hong-Lian;Cui, Cui;Chen, Li-Zhen;Zeng, Yi-Xin;Jia, Wei-Hua

Background : Lifestyle behaviors have been widely reported to influence the survival of patients with head and neck cancer. However, the relationship between pretreatment lifestyle behaviors and survival among patients with nasopharyngeal carcinoma (NPC) is unclear. Methods : A prospective cohort study was designed to determine the relationship between lifestyle behaviors and survival in 1,533 NPC patients recruited from October 2005 to October 2007. Pretreatment lifestyle behaviors (such as body-mass index [BMI], smoking, alcohol, diet) of the patients were investigated. Univariate and multivariate proportional-hazards models were used to assess the impact of lifestyle behaviors on patient survival. Results : Smoking was a predictor of survival; both current smokers (hazard ratio [HR] = 1.88; 95% CI, 1.33 to 2.65) and heavy smokers (≥25 Pack-years; HR = 1.84; 95% CI, 1.30 to 2.60) showed associations with poor survival. Higher BMI was significantly associated with a lower risk of ...

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

Menée sur 146 patients présentant des métastases ganglionnaires après cystectomie radicale pour un cancer de la vessie (durée médiane de suivi : 54 mois), cette étude évalue, du point de vue de la survie sans récidive et de la survie globale, la valeur pronostique d'un système américain de stadification ganglionnaire

Critical Evaluation of the American Joint Committee on Cancer TNM Nodal Staging System in Patients with Lymph NodePositive Disease after Radical Cystectomy
• European urology, sous presse, 2012 (résumé)

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Menée sur 146 patients présentant des métastases ganglionnaires après cystectomie radicale pour un cancer de la vessie (durée médiane de suivi : 54 mois), cette étude évalue, du point de vue de la survie sans récidive et de la survie globale, la valeur pronostique d'un système américain de stadification ganglionnaire

“Critical Evaluation of the American Joint Committee on Cancer TNM Nodal Staging System in Patients with Lymph NodePositive Disease after Radical Cystectomy”

• H. Max Bruins;Ryan, P. Dorin;Barbara, Rubino;Gus, Miranda;Jie, Cai;Siamak, Daneshmand;Eila, C. Skinner

Background : The current 7th edition of the American Joint Committee on Cancer TNM staging system for bladder cancer stages lymph node (LN)–positive disease based on LN location rather than LN size. In addition, common iliac LNs are now considered regional LNs. Whether these changes improve prognostication for node-positive patients, however, remains unclear. Objective : To investigate whether the 7th edition of the TNM nodal staging system provides superior prognostication compared with the 6th edition. Design, setting, and participants : Patients between 2002 and 2008 with LN metastases after radical cystectomy combined with extended or superextended LN dissection were included. Patients were staged using both TNM staging systems. Median follow-up was 54 mo. Outcome measurements and statistical analysis : Kaplan-Meier curves were used to estimate overall survival (OS) and recurrence-free survival (RFS). Log-rank tests and Cox proportional hazard regression models were used to test ...

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

Menée sur 35 patients atteints d'un carcinome à cellules rénales de stade avancé et traité par des inhibiteurs de tyrosine kinase, cette étude montre qu'une tomographie numérique par émission de positrons à base de fluorodésoxyglucose (18F) peut permettre, à partir de l'analyse de l'évolution de la taille des tumeurs, de prédire précocement la réponse au traitement

Early Assessment by FDG-PET/CT of Patients with Advanced Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors is Predictive of Disease Course
• BMC Cancer, Vol. 12 (1), pp. 162, 2012 (article en libre accès)

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Menée sur 35 patients atteints d'un carcinome à cellules rénales de stade avancé et traité par des inhibiteurs de tyrosine kinase, cette étude montre qu'une tomographie numérique par émission de positrons à base de fluorodésoxyglucose (18F) peut permettre, à partir de l'analyse de l'évolution de la taille des tumeurs, de prédire précocement la réponse au traitement

“Early Assessment by FDG-PET/CT of Patients with Advanced Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors is Predictive of Disease Course”

• Ueno, Daiki;Yao, Masahiro;Tateishi, Ukihide;Minamimoto, Ryogo;Makiyama, Kazuhide;Hayashi, Narihiko;Sano, Futoshi;Murakami, Takayuki;Kishida, Takeshi;Miura, Takeshi;Kobayashi, Kazuki;Noguchi, Sumio;Ikeda, Ichiro;Ohgo, Yoshiharu;Inoue, Tomio;Kubota, Yoshinobu;Nakaigawa, Noboru

Purpose We reported previously that 18F-2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) had potential for evaluating early response to treatment by tyrosine kinase inhibitors (TKIs) in advanced renal cell carcinoma (RCC). This time we investigated the relation of the early assessment by FDG PET/CT to long-term prognosis with an expanded number of patients and period of observation.METHODS:Patients for whom TKI treatment for advanced RCC was planned were enrolled. FDG PET/CT was performed before TKI treatment and after one month of TKI treatment. The relations of the FDGPET/CT assessment to progression free survival (PFS) and overall survival (OS) were investigated.RESULTS:Thirty-five patients were enrolled (sunitinib 19 cases, sorafenib 16 cases). The patients with RCC showing high SUVmax in pretreatment FDG PET/CT demonstrated short PFS (P =0.024, hazard ratio 1.137, 95% CI 1.017-1.271) and short OS (P =0.004, hazard ratio 1.210 95% CI ...

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

A partir de 247 échantillons tumoraux prélevés sur des patients atteints de leucémie lymphocytaire chronique, cette étude montre qu'une analyse quantitative de la méthylation d'un dinucléotide CpG situé sur le gène ZAP-70 permet de prédire le pronostic associé à la maladie

Quantitative DNA Methylation Analysis Identifies a Single CpG Dinucleotide Important for ZAP-70 Expression and Predictive of Prognosis in Chronic Lymphocytic Leukemia
• Journal of Clinical Oncology, sous presse, 2012 (résumé)

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A partir de 247 échantillons tumoraux prélevés sur des patients atteints de leucémie lymphocytaire chronique, cette étude montre qu'une analyse quantitative de la méthylation d'un dinucléotide CpG situé sur le gène ZAP-70 permet de prédire le pronostic associé à la maladie

“Quantitative DNA Methylation Analysis Identifies a Single CpG Dinucleotide Important for ZAP-70 Expression and Predictive of Prognosis in Chronic Lymphocytic Leukemia”

• Claus, Rainer;Lucas, David M.;Stilgenbauer, Stephan;Ruppert, Amy S.;Yu, Lianbo;Zucknick, Manuela;Mertens, Daniel;Bühler, Andreas;Oakes, Christopher C.;Larson, Richard A.;Kay, Neil E.;Jelinek, Diane F.;Kipps, Thomas J.;Rassenti, Laura Z.;Gribben, John G.;Döhner, Hartmut;Heerema, Nyla A.;Marcucci, Guido;Plass, Christoph;Byrd, John C.

Purpose Increased ZAP-70 expression predicts poor prognosis in chronic lymphocytic leukemia (CLL). Current methods for accurately measuring ZAP-70 expression are problematic, preventing widespread application of these tests in clinical decision making. We therefore used comprehensive DNA methylation profiling of the ZAP-70 regulatory region to identify sites important for transcriptional control.Patients and Methods High-resolution quantitative DNA methylation analysis of the entire ZAP-70 gene regulatory regions was conducted on 247 samples from patients with CLL from four independent clinical studies.Results Through this comprehensive analysis, we identified a small area in the 5` regulatory region of ZAP-70 that showed large variability in methylation in CLL samples but was universally methylated in normal B cells. High correlation with mRNA and protein expression, as well as activity in promoter reporter assays, revealed that within this differentially methylated region, a single ...

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

Ressources et infrastructures (Dépistage)

Cet article analyse les enjeux cliniques et économiques associés à l'émergence de la médecine génomique

The business value and cost–effectiveness of genomic medicine
• Personalized Medicine, Vol. 9 (3), pp. 265-286, 2012 (article en libre accès)

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Cet article analyse les enjeux cliniques et économiques associés à l'émergence de la médecine génomique

“The business value and cost–effectiveness of genomic medicine”

• Crawford, James M.;Aspinall, Mara G.

Genomic medicine offers the promise of more effective diagnosis and treatment of human diseases. Genome sequencing early in the course of disease may enable more timely and informed intervention, with reduced healthcare costs and improved long-term outcomes. However, genomic medicine strains current models for demonstrating value, challenging efforts to achieve fair payment for services delivered, both for laboratory diagnostics and for use of molecular information in clinical management. Current models of healthcare reform stipulate that care must be delivered at equal or lower cost, with better patient and population outcomes. To achieve demonstrated value, genomic medicine must overcome many uncertainties: the clinical relevance of genomic variation; potential variation in technical performance and/or computational analysis; management of massive information sets; and must have available clinical interventions that can be informed by genomic analysis, so as to attain more favorable ...