Dépistage, diagnostic et pronostic

Menée sur 22 lignées cellulaires de cancer du poumon, cette étude suggère que la mesure d'une surexpression de JAK1 pourrait servir de biomarqueur prédictif de la réponse à l'enzastaurine

• Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  Menée sur 22 lignées cellulaires de cancer du poumon, cette étude suggère que la mesure d'une surexpression de JAK1 pourrait servir de biomarqueur prédictif de la réponse à l'enzastaurine

  “Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules”

  • Shimokawa, T.;Seike, M.;Soeno, C.;Uesaka, H.;Miyanaga, A.;Mizutani, H.;Kitamura, K.;Minegishi, Y.;Noro, R.;Okano, T.;Yoshimura, A.;Gemma, A.

  Background: Enzastaurin, an oral serine–threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase C β. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. Methods: We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines. Results: We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity ...

  
  

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

Cet article passe en revue les perspectives offertes par l'exploitation des défauts de réparation de l'ADN pour le développement de biomarqueurs de la réponse thérapeutique dans le cancer du poumon

• The potential of exploiting DNA-repair defects for optimizing lung cancer treatment
  • Nature Reviews Clinical Oncology, sous presse, 2012 (résumé)
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  Cet article passe en revue les perspectives offertes par l'exploitation des défauts de réparation de l'ADN pour le développement de biomarqueurs de la réponse thérapeutique dans le cancer du poumon

  “The potential of exploiting DNA-repair defects for optimizing lung cancer treatment”

  • Postel-Vinay, Sophie;Vanhecke, Elsa;Olaussen, Ken A.;Lord, Christopher J.;Ashworth, Alan;Soria, Jean-Charles

  The tumor genome is commonly aberrant as a consequence of mutagenic insult and incomplete DNA repair. DNA repair as a therapeutic target has recently received considerable attention owing to the promise of drugs that target tumor-specific DNA-repair enzymes and potentiate conventional cytotoxic therapy through mechanism-based approaches, such as synthetic lethality. Treatment for non-small-cell lung cancer (NSCLC) consists mainly of platinum-based chemotherapy regimens and improvements are urgently needed. Optimizing treatment according to tumor status for DNA-repair biomarkers, such as ERCC1, BRCA1 or RRM1, could predict response to platinum, taxanes and gemcitabine-based therapies, respectively, and might improve substantially the response of individual patients' tumors. Finally, recent data on germline variation in DNA-repair genes may also be informative. Here, we discuss how a molecular and functional DNA-repair classification of NSCLC may aid clinical decision making and improve ...

  
  

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

Menée sur 527 patients atteints d'un cancer du poumon non à petites cellules de stade I, cette étude identifie des signatures basées sur l'expression de micro-ARNs en association avec la survie des patients

• MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer
  • Carcinogenesis, sous presse, 2012 (résumé)
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  Menée sur 527 patients atteints d'un cancer du poumon non à petites cellules de stade I, cette étude identifie des signatures basées sur l'expression de micro-ARNs en association avec la survie des patients

  “MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer”

  • Lu, Yan;Govindan, Ramaswamy;Wang, Liang;Liu, Peng-yuan;Goodgame, Boone;Wen, Weidong;Sezhiyan, Ananth;Li, Ya-fei;Hua, Xing;Wang, Yian;Yang, Ping;You, Ming

  About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19 to 25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling V2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145* which inhibit cell invasion and metastasis. Two miRNA ...

  
  

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

Menée sur trois cohortes européennes incluant 189 patients pédiatriques atteints d'un épendymome, cette étude évalue l'association entre un gain du chromosome 1q25 et la survie des patients

• Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification
  • Clinical Cancer Research, sous presse, 2012 (résumé)
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  Menée sur trois cohortes européennes incluant 189 patients pédiatriques atteints d'un épendymome, cette étude évalue l'association entre un gain du chromosome 1q25 et la survie des patients

  “Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification”

  • Kilday, John-Paul;Mitra, Biswaroop;Domerg, Caroline;Ward, Jennifer;Andreiuolo, Felipe;Osteso-Ibanez, Teresa;Mauguen, Audrey;Varlet, Pascale;Le Deley, Marie-Cecile;Lowe, James;Ellison, David W.;Gilbertson, Richard J.;Coyle, Beth;Grill, Jacques;Grundy, Richard Guy

  Purpose: The high incidence of recurrence and unpredictable clinical outcome for pediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. We therefore evaluated 1q25 gain across three age and treatment defined European clinical trial cohorts of pediatric intracranial ependymoma. Experimental Design: Frequency of 1q gain was assessed across 48 ependymomas (42 primary, 6 recurrent) using Affymetrix® 500K SNP arrays. Gain of 1q25 was then evaluated by interphase FISH across 189 tumors treated on the CCLG/SIOP CNS9204 (n=60) and BBSFOP (n=65) adjuvant chemotherapy trials, or with primary post-operative radiotherapy (SIOP CNS9904/RT, n=64). Results were correlated with clinical, histological and survival data. Results: Gain of 1q was the most frequent imbalance in primary (7/42, 17 %) and recurrent ependymomas (2/6, 33 %). Gain of 1q25 was an independent predictor of tumor progression across the pooled trial cohort (HR ...

  
  

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

Menée sur 2 016 patients atteints d'un sarcome et soignés dans des centres italiens et français, cette étude évalue l'intérêt d'une deuxième opinion pour améliorer la précision du diagnostic

• Sarcoma: concordance between initial diagnosis and centralized expert review in a population-based study within three European regions
  • Annals of Oncology, sous presse, 2012 (résumé)
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  Menée sur 2 016 patients atteints d'un sarcome et soignés dans des centres italiens et français, cette étude évalue l'intérêt d'une deuxième opinion pour améliorer la précision du diagnostic

  “Sarcoma: concordance between initial diagnosis and centralized expert review in a population-based study within three European regions”

  • Ray-Coquard, I.;Montesco, M. C.;Coindre, J. M.;Dei Tos, A. P.;Lurkin, A.;Ranchère-Vince, D.;Vecchiato, A.;Decouvelaere, A. V.;Mathoulin-Pélissier, S.;Albert, S.;Cousin, P.;Cellier, D.;Toffolatti, L.;Rossi, C. R.;Blay, J. Y.

  Background: Sarcomas represent a heterogeneous group of tumors. Accurate determination of histological diagnosis and prognostic factors is critical for the delineation of treatment strategies. The contribution of second opinion (SO) to improve diagnostic accuracy has been suggested for sarcoma but has never been established in population-based studies.Methods: Histological data of patients diagnosed with sarcoma in Rhone-Alpes (France), Veneto (Italy) and Aquitaine (France) over a 2-year period were collected. Initial diagnoses were systematically compared with SO from regional and national experts.Results: Of 2016 selected patients, 1463 (73%) matched the inclusion criteria and were analyzed. Full concordance between primary diagnosis and SO (the first pathologist and the expert reached identical conclusions) was observed in 824 (56%) cases, partial concordance (identical diagnosis of connective tumor but different grade or histological subtype) in 518 (35%) cases and complete ...

  
  

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

Menée sur 95 patients atteints d'un sarcome des tissus mous, cette étude évalue l'intérêt d'une tomographie par émissions de positons au 18F-fluorodésoxyglucose, après un premier cycle de chimiothérapie néoadjuvante, pour prédire la survie des patients

• 18F-FDG-PET/CT imaging as an Early Survival Predictor in Patients with Primary High Grade Soft Tissue Sarcomas undergoing Neoadjuvant Therapy
  • Clinical Cancer Research, sous presse, 2012 (résumé)
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  Menée sur 95 patients atteints d'un sarcome des tissus mous, cette étude évalue l'intérêt d'une tomographie par émissions de positons au 18F-fluorodésoxyglucose, après un premier cycle de chimiothérapie néoadjuvante, pour prédire la survie des patients

  “18F-FDG-PET/CT imaging as an Early Survival Predictor in Patients with Primary High Grade Soft Tissue Sarcomas undergoing Neoadjuvant Therapy”

  • Herrmann, Ken;Benz, Matthias R.;Czernin, Johannes;Allen-Auerbach, Martin S.;Tap, William D.;Dry, Sarah M.;Schuster, Tibor;Eckardt, Jeff J.;Phelps, Michael E.;Weber, Wolfgang A.;Eilber, Fritz C.

  Purpose:Neoadjuvant therapy is associated with considerable toxicity and limited survival benefits in patients with soft tissue sarcoma (STS). We prospectively evaluated whether 18F-FDG PET/CT imaging after the initial cycle of neoadjuvant therapy could predict overall survival in these patients. Experimental Design:39 patients underwent 18F-FDG PET/CT prior to and after one cycle of neoadjuvant therapy. 56 patients underwent end of treatment PET. Overall survival was, among others, correlated with changes of SUVpeak and histopathology. Results:One-, two- and five-year survival rates were 95±3.0%, 86±4.6% and 68±6.6%, respectively. Median time to death was 30.9 months (mean: 27.7; range: 6.9 - 50.1). Optimal cut-offs for early and late decreases in SUV peak (26% and 57%, respectively) were significant predictors of survival in univariate survival analysis (p=0.041, HR=0.27 95%CI: 0.08 to 0.95, and p=0.045, HR=0.31 95%CI: 0.10 to 0.98). Seven/15 early PET non-responders but only ...

  
  

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

Cette revue systématique de la littérature évalue la stratégie de surveillance active pour la prise en charge des patients diagnostiqués avec un cancer localisé de la prostate

• Active Surveillance in Men With Localized Prostate Cancer
  • Annals of Internal Medicine, sous presse, 2012 (article en libre accès)
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  Cette revue systématique de la littérature évalue la stratégie de surveillance active pour la prise en charge des patients diagnostiqués avec un cancer localisé de la prostate

  “Active Surveillance in Men With Localized Prostate Cancer”

  • Dahabreh, Issa J.;Chung, Mei;Balk, Ethan M.;Yu, Winifred W.;Mathew, Paul;Lau, Joseph;Ip, Stanley

  Background: Active surveillance (AS) and watchful waiting (WW) have been proposed as management strategies for low-risk, localized prostate cancer.Purpose: To systematically review strategies for observational management of prostate cancer (AS or WW), factors affecting their utilization, and comparative effectiveness of observational management versus immediate treatment with curative intent.Data Sources: MEDLINE and Cochrane databases (from inception to August 2011).Study Selection: Screened abstracts and reviewed full-text publications to identify eligible studies.Data Extraction: One reviewer extracted data, and another verified quantitative data. Two independent reviewers rated study quality and strength of evidence for comparative effectiveness.Data Synthesis: Sixteen independent cohorts defined AS, 42 studies evaluated factors that affect the use of observational strategies, and 2 evidence reports and 22 recent studies reported comparisons of WW versus treatment with curative ...

  
  
• National Institutes of Health State-of-the-Science Conference: Role of Active Surveillance in the Management of Men With Localized Prostate Cancer
  • Annals of Internal Medicine, sous presse, 2012 (article en libre accès)
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  Cette revue systématique de la littérature évalue la stratégie de surveillance active pour la prise en charge des patients diagnostiqués avec un cancer localisé de la prostate

  “National Institutes of Health State-of-the-Science Conference: Role of Active Surveillance in the Management of Men With Localized Prostate Cancer”

  • Ganz, Patricia A. ; Barry, John M. ; Burke, Wylie ; Col, Nananda F. ; Corso, Phaedra S. ; Dodson, Everett ; Hammond, M. Elizabeth ; Kogan, Barry A. ; Lynch, Charles F. ; Newcomer, Lee ; Seifter, Eric J. ; Tooze, Janet A. ; Viswanath, Kasisomayajula ; Wessells, Hunter

  
  

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

A partir de données portant sur 4 cohortes ayant inclus 2 902 patients atteints d'un syndrome myélodysplasique, cette étude évalue l'intérêt d'un nouveau système de score cytogénétique pour estimer le pronostic

• New Comprehensive Cytogenetic Scoring System for Primary Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia After MDS Derived From an International Database Merge
  • Journal of Clinical Oncology, sous presse, 2012 (résumé)
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  A partir de données portant sur 4 cohortes ayant inclus 2 902 patients atteints d'un syndrome myélodysplasique, cette étude évalue l'intérêt d'un nouveau système de score cytogénétique pour estimer le pronostic

  “New Comprehensive Cytogenetic Scoring System for Primary Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia After MDS Derived From an International Database Merge”

  • Schanz, Julie;Tüchler, Heinz;Solé, Francesc;Mallo, Mar;Luño, Elisa;Cervera, José;Granada, Isabel;Hildebrandt, Barbara;Slovak, Marilyn L.;Ohyashiki, Kazuma;Steidl, Christian;Fonatsch, Christa;Pfeilstöcker, Michael;Nösslinger, Thomas;Valent, Peter;Giagounidis, Aristoteles;Aul, Carlo;Lübbert, Michael;Stauder, Reinhard;Krieger, Otto;Garcia-Manero, Guillermo;Faderl, Stefan;Pierce, Sherry;Le Beau, Michelle M.;Bennett, John M.;Greenberg, Peter;Germing, Ulrich;Haase, Detlef

  Purpose The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients.Patients and Methods Patients were included from the German-Austrian MDS Study Group (n = 1,193), the International MDS Risk Analysis Workshop (n = 816), the Spanish Hematological Cytogenetics Working Group (n = 849), and the International Working Group on MDS Cytogenetics (n = 44) databases. Patients with primary MDS and oligoblastic acute myeloid leukemia (AML) after MDS treated with supportive care only were evaluated for overall survival (OS) and AML evolution. Internal validation by bootstrap analysis and external validation in an independent patient cohort were performed ...

  
  
• Myelodysplastic Syndromes: It Is All in the Genes
  • Journal of Clinical Oncology, sous presse, 2012 (éditorial en libre accès)
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  A partir de données portant sur 4 cohortes ayant inclus 2 902 patients atteints d'un syndrome myélodysplasique, cette étude évalue l'intérêt d'un nouveau système de score cytogénétique pour estimer le pronostic

  “Myelodysplastic Syndromes: It Is All in the Genes”

  • Sekeres, Mikkael A.

  
  

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

Cet article passe en revue les travaux récents sur l'intérêt de l'IRM dynamique avec réhaussement de contraste dans le cadre des essais cliniques de thérapies ciblées antivasculaires

• Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies
  • Nature Reviews Clinical Oncology, sous presse, 2012 (résumé)
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  Cet article passe en revue les travaux récents sur l'intérêt de l'IRM dynamique avec réhaussement de contraste dans le cadre des essais cliniques de thérapies ciblées antivasculaires

  “Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies”

  • O'Connor, James P. B.;Jackson, Alan;Parker, Geoff J. M.;Roberts, Caleb;Jayson, Gordon C.

  About 100 early-phase clinical trials and investigator-led studies of targeted antivascular therapies—both anti-angiogenic and vascular-targeting agents—have reported data derived from T1-weighted dynamic contrast-enhanced (DCE)-MRI. However, the role of DCE-MRI for decision making during the drug-development process remains controversial. Despite well-documented guidelines on image acquisition and analysis, several key questions concerning the role of this technique in early-phase trial design remain unanswered. This Review describes studies of single-agent antivascular therapies, in which DCE-MRI parameters are incorporated as pharmacodynamic biomarkers. We discuss whether these parameters, such as volume transfer constant (Ktrans), are reproducible and reliable biomarkers of both drug efficacy and proof of concept, and whether they assist in dose selection and drug scheduling for subsequent phase II trials. Emerging evidence indicates that multiparametric analysis of DCE-MRI ...

  
  

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

Menée sur 74 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade localement avancé, cette étude montre une association entre divers marqueurs des cellules souches de cancer et la réponse à une chimioradiothérapie

• Cancer stem cell phenotype relates to radio-chemotherapy outcome in locally advanced squamous cell head-neck cancer
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  Menée sur 74 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade localement avancé, cette étude montre une association entre divers marqueurs des cellules souches de cancer et la réponse à une chimioradiothérapie

  “Cancer stem cell phenotype relates to radio-chemotherapy outcome in locally advanced squamous cell head-neck cancer”

  • Koukourakis, M. I.;Giatromanolaki, A.;Tsakmaki, V.;Danielidis, V.;Sivridis, E.

  Background : Cancer stem cells (CSCs) tend to repopulate malignant tumours during radiotherapy and, therefore, prolongation of the overall treatment time may result in radiotherapy failure. Thus, an estimate of the number of CSCs in tumour biopsies may prove most useful in predicting resistance to radiotherapy and a guide for development therapies aimed to eradicate a cancer cell population with effects on radiotherapy-related cancer regrowth. Methods : The CSC population was investigated semi-quantitatively in 74 locally advanced squamous cell head–neck cancers (HNSCC) from an equal number of patients, treated with accelerated platinum-based radiotherapy. A standard immunohistochemical technique and the CSC markers CD44, CD24, Oct4, integrin- β1 and aldehyde dehydrogenase isoform 1A1 (ALDHA1) was used, in parallel with the proliferation marker MIB-1. The results were correlated with the site of the tumour, the MIB-1 index, the tumour grade and stage, and prognosis. Results :The ...

  
  

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

Menée sur 314 patients atteints de myélofibrose primitive ou de syndrome myélodysplasique, cette étude montre une association entre le niveau plasmatique des chaînes légères libres des immunoglobulines polyclonales et la survie des patients

• Polyclonal Immunoglobulin Free Light Chain Levels Predict Survival in Myeloid Neoplasms
  • Journal of Clinical Oncology, sous presse, 2012 (résumé)
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  Menée sur 314 patients atteints de myélofibrose primitive ou de syndrome myélodysplasique, cette étude montre une association entre le niveau plasmatique des chaînes légères libres des immunoglobulines polyclonales et la survie des patients

  “Polyclonal Immunoglobulin Free Light Chain Levels Predict Survival in Myeloid Neoplasms”

  • Pardanani, Animesh;Lasho, Terra L.;Finke, Christy M.;Rajkumar, S. Vincent;Singh, Preet Paul;Ketterling, Rhett P.;Hanson, Curtis A.;Katzmann, Jerry A.;Tefferi, Ayalew

  Purpose We hypothesized that surrogate markers of host immune response may predict survival in myeloid malignancies. Because of immediate practical applicability, we chose plasma immunoglobulin free light chain (FLC) concentration as the biomarker of interest.Patients and Methods Two independent cohorts of patients with primary myelofibrosis (PMF) or myelodysplastic syndromes (MDS) were studied. Kappa (κ) and lambda (λ) FLCs were measured by a quantitative nephelometric assay. Patients with monoclonal FLC were excluded.Results Values that were above the upper limit of normal for κ or λ FLC were documented in 33% of 240 patients with PMF and 46% of 74 patients with MDS. Increased FLC was significantly associated with increased creatinine, and advanced age in PMF (P < .001) and hemoglobin less than 10 g/dL in MDS (P = .005). In multivariable analysis, increased FLC predicted shortened survival in both PMF and MDS, independent of age, creatinine, and other conventional risk factors. ...

  
  

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

Menée à partir de questionnaires auprès de 204 patientes sous traitement pour un cancer du sein, cette étude prospective analyse les facteurs permettant de prédire leur adhésion à un programme de surveillance par mammographie

• Prospective Study of Factors Predicting Adherence to Surveillance Mammography in Women Treated for Breast Cancer
  • Journal of Clinical Oncology, sous presse, 2012 (résumé)
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  Menée à partir de questionnaires auprès de 204 patientes sous traitement pour un cancer du sein, cette étude prospective analyse les facteurs permettant de prédire leur adhésion à un programme de surveillance par mammographie

  “Prospective Study of Factors Predicting Adherence to Surveillance Mammography in Women Treated for Breast Cancer”

  • Shelby, Rebecca A.;Scipio, Cindy D.;Somers, Tamara J.;Soo, Mary Scott;Weinfurt, Kevin P.;Keefe, Francis J.

  Purpose This prospective study examined the factors that predicted sustained adherence to surveillance mammography in women treated for breast cancer.Methods Breast cancer survivors (N = 204) who were undergoing surveillance mammography completed questionnaires assessing mammography-related anticipatory anxiety, persistent breast pain, mammography pain, and catastrophic thoughts about mammography pain. Adherence to mammography in the following year was assessed.Results In the year after study entry, 84.8% of women (n = 173) returned for a subsequent mammogram. Unadjusted associations showed that younger age, shorter period of time since surgery, and having upper extremity lymphedema were associated with lower mammography adherence. Forty percent of women reported moderate to high levels of mammography pain (score of ≥ 5 on a 0 to 10 scale). Although mammography pain was not associated with adherence, higher levels of mammography-related anxiety and pain catastrophizing were ...

  
  

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

Mené sur 503 patientes atteintes d'un cancer du sein de stade précoce traité par l'exémestane ou le létrozole, deux inhibiteurs de l'aromatase, cet essai prospectif multicentrique évalue la possibilité de remplacer un inhibiteur par un autre en cas d'intolérance symptomatique durant le traitement

• Predictors of Aromatase Inhibitor Discontinuation as a Result of Treatment-Emergent Symptoms in Early-Stage Breast Cancer
  • Journal of Clinical Oncology, sous presse, 2012 (résumé)
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  Mené sur 503 patientes atteintes d'un cancer du sein de stade précoce traité par l'exémestane ou le létrozole, deux inhibiteurs de l'aromatase, cet essai prospectif multicentrique évalue la possibilité de remplacer un inhibiteur par un autre en cas d'intolérance symptomatique durant le traitement

  “Predictors of Aromatase Inhibitor Discontinuation as a Result of Treatment-Emergent Symptoms in Early-Stage Breast Cancer”

  • Henry, N. Lynn;Azzouz, Faouzi;Desta, Zereunesay;Li, Lang;Nguyen, Anne T.;Lemler, Suzanne;Hayden, Jill;Tarpinian, Karineh;Yakim, Elizabeth;Flockhart, David A.;Stearns, Vered;Hayes, Daniel F.;Storniolo, Anna Maria

  Purpose Aromatase inhibitors (AIs) are effective for treatment of hormone receptor–positive breast cancer, but adherence and persistence with therapy are poor. Predictors of treatment discontinuation are not clearly defined. It is unknown whether patients with intolerable toxicity from one AI are able to tolerate another.Patients and Methods Women with early-stage breast cancer initiating AI therapy were enrolled onto a multicenter, prospective, open-label randomized trial of exemestane versus letrozole. Patients completed symptom questionnaires at baseline and serially during therapy. Patients who developed AI-associated intolerable symptoms and discontinued treatment were given the option to switch to the other study AI after a 2- to 8-week washout period.Results Of the 503 enrolled women, 32.4% discontinued initial AI therapy within 2 years because of adverse effects; 24.3% discontinued specifically because of musculoskeletal symptoms. Median time to treatment discontinuation as ...

  
  

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

Menée sur 267 patientes atteintes d'un cancer métastatique du sein, cette étude compare les performances de divers marqueurs sanguins (cellules tumorales circulantes et marqueurs sériques) pour prédire la survie sans progression

• Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer : a prospective observational study
  • Breast Cancer Research, Vol. 14 (1), pp. R29, 2012 (article en libre accès)
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  Menée sur 267 patientes atteintes d'un cancer métastatique du sein, cette étude compare les performances de divers marqueurs sanguins (cellules tumorales circulantes et marqueurs sériques) pour prédire la survie sans progression

  “Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer : a prospective observational study”

  • Bidard, Francois-Clement;Hajage, David;Bachelot, Thomas;Delaloge, Suzette;Brain, Etienne;Campone, Mario;Cottu, Paul;Beuzeboc, Philippe;Rolland, Emilie;Mathiot, Claire;Pierga, Jean-Yves

  INTRODUCTION:Circulating tumors cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum markers levels are also used for the same purpose, and no clear comparison as been reported to date.METHODS:The IC 2006-04 enrolled prospectively 267 metastatic breast cancer patients treated by first line chemotherapy and confirmed that CTC levels are an independent prognostic factor for PFS and Overall survival (OS). A secondary pre-planned endpoint was to compare prospectively the positivity rates and the value of CTC (CellSearch(R)), of serum tumor markers (CEA, CA 15-3, CYFRA 21-1), and of serum non-tumor markers (LDH, ALP) at baseline and under treatment for PFS prediction, independently from the other known prognostic factors, using univariate analyses and concordance indexes.RESULTS:90% of ...

  
  

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

Menée à partir d'échantillons tumoraux prélevés sur 223 patients atteints d'un carcinome épidermoïde de l'œsophage, cette étude montre qu'une surexpression tumorale de la protéine PFTK1 permet de prédire la résistance à une chimiothérapie

• Overexpression of PFTK1 predicts resistance to chemotherapy in patients with oesophageal squamous cell carcinoma
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  Menée à partir d'échantillons tumoraux prélevés sur 223 patients atteints d'un carcinome épidermoïde de l'œsophage, cette étude montre qu'une surexpression tumorale de la protéine PFTK1 permet de prédire la résistance à une chimiothérapie

  “Overexpression of PFTK1 predicts resistance to chemotherapy in patients with oesophageal squamous cell carcinoma”

  • Miyagaki, H.;Yamasaki, M.;Miyata, H.;Takahashi, T.;Kurokawa, Y.;Nakajima, K.;Takiguchi, S.;Fujiwara, Y.;Ishii, H.;Tanaka, F.;Mori, M.;Doki, Y.

  Background : Recently, PFTK1 was identified as a member of the cyclin-dependent kinase family; however, its expression and clinical significance in oesophageal squamous cell carcinoma (ESCC) have not been evaluated. Methods : PFTK1 expression was initially examined by expression microarray in 77 ESCC patients. Using independent samples of 223 patients, PFTK1 expression was evaluated immunohistochemically to assess the relationship between expression and various clinicopathological parameters. The association between PFTK1 and the response to chemotherapy was also investigated in pretreatment samples of 85 patients who received chemotherapy as first treatment. Results : Significant upregulation of PFTK1 expression was noted in ESCC compared with normal epithelium. PFTK1 expression was positive in 51.6% (115 out of 223) of the tumours, but did not correlate with any clinicopathological parameter. The 5-year overall survival rate was poorer in patients positive for PFTK1 (43.6%) than ...

  
  

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

A partir de données portant sur 8 539 greffes de cellules hématopoïétiques issues de donneurs non apparentés, cette étude rétrospective évalue l'effet du degré de disparité entre l'épitope des lymphocytes T et les antigènes HLA-DPB1 sur la mortalité et le risque de récidive

• Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study
  • The Lancet Oncology, sous presse, 2012 (résumé)
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  A partir de données portant sur 8 539 greffes de cellules hématopoïétiques issues de donneurs non apparentés, cette étude rétrospective évalue l'effet du degré de disparité entre l'épitope des lymphocytes T et les antigènes HLA-DPB1 sur la mortalité et le risque de récidive

  “Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study”

  • Fleischhauer, Katharina;Shaw, Bronwen E.;Gooley, Theodore;Malkki, Mari;Bardy, Peter;Bignon, Jean-Denis;Dubois, Valérie;Horowitz, Mary M.;Madrigal, J. Alejandro;Morishima, Yasuo;Oudshoorn, Machteld;Ringden, Olle;Spellman, Stephen;Velardi, Andrea;Zino, Elisabetta;Petersdorf, Effie W.

  The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation. HLA and clinical data for related-donor transplantations submitted to the International Histocompatibility Working Group in haemopoietic-cell transplantation were analysed retrospectively. HLA-DPB1 T-cell-epitope groups were assigned according to a functional algorithm based on alloreactive T-cell crossreactivity patterns. Recipients ...

  
  
• Permissive mismatches for blood and marrow transplantation
  • The Lancet Oncology, sous presse, 2012 (commentaire)
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  A partir de données portant sur 8 539 greffes de cellules hématopoïétiques issues de donneurs non apparentés, cette étude rétrospective évalue l'effet du degré de disparité entre l'épitope des lymphocytes T et les antigènes HLA-DPB1 sur la mortalité et le risque de récidive

  “Permissive mismatches for blood and marrow transplantation”

  • Szabolcs, Paul

  
  

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

Menée sur 527 patients atteints d'un cancer colorectal, cette étude prospective évalue l'association entre le niveau d'expression tumorale de la protéine SATB2, la survie des patients et la réponse à un traitement adjuvant ou néoadjuvant

• A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  Menée sur 527 patients atteints d'un cancer colorectal, cette étude prospective évalue l'association entre le niveau d'expression tumorale de la protéine SATB2, la survie des patients et la réponse à un traitement adjuvant ou néoadjuvant

  “A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer”

  • Eberhard, J.;Gaber, A.;Wangefjord, S.;Nodin, B.;Uhlen, M.;Ericson Lindquist, K.;Jirstrom, K.

  Background : Special AT-rich sequence-binding protein 2 (SATB2) is a novel diagnostic marker of colorectal cancer (CRC), and loss of SATB2 has been linked to poor survival from the disease. In this study, we validated the prognostic ability of SATB2 expression in a large, prospective CRC cohort. Methods : Immunohistochemical SATB2 expression was assessed in 527 incident CRC cases from the Malmö Diet and Cancer Study. Kaplan–Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB2 expression on cancer-specific survival (CSS) and overall survival (OS). Results : High SATB2 expression was associated with a prolonged CSS in the full cohort (hazard ratio (HR)=0.61; 95% CI 0.41–0.92) and in colon cancer (HR=0.39; 95% CI 0.20–0.75), remaining significant in multivariable analysis of colon cancer (HR=0.49; 95% CI 0.25–0.96), with similar findings for OS. In curatively resected stage III-IV patients, a significant benefit from adjuvant and/or ...

  
  

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

Menée auprès de 140 942 femmes âgées de 66 à 89 ans dont 2 993 atteintes d'un cancer du sein, cette étude compare les avantages et les inconvénients d'une mammographie annuelle et d'une mammographie biennale en fonction de l'âge des participantes et de l'indice de comorbidité de Charlson

• Benefits and Harms of Screening Mammography Frequency by Age and Comorbidity Score
  • Cancer Epidemiology Biomarkers & Prevention, sous presse, 2012 (résumé)
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  Menée auprès de 140 942 femmes âgées de 66 à 89 ans dont 2 993 atteintes d'un cancer du sein, cette étude compare les avantages et les inconvénients d'une mammographie annuelle et d'une mammographie biennale en fonction de l'âge des participantes et de l'indice de comorbidité de Charlson

  “Benefits and Harms of Screening Mammography Frequency by Age and Comorbidity Score”

  • D, Braithwaite;W, Zhu;R, Hubbard;ES, O'Meara;DL, Miglioretti;B, Geller;K, Dittus;K, Wernli;D, Moore;K, Kerlikowske

  Background: There is uncertainty about the appropriate use of screening mammography in older women. We compared the benefits and harms of screening mammography frequency according to age and comorbidity scores.Methods: We conducted analyses within a prospective cohort study of four mammography registries in the Breast Cancer Surveillance Consortium that had mammography data linked to Medicare claims information. Participants included 137,949 women aged 66–89 years without breast cancer and 2,993 women with breast cancer. We estimated odds of advanced (IIb, III, IV) stage, large tumor size (>20 millimeters), and estrogen receptor (ER) negative tumors and cumulative probability of false-positive mammography after 10 years of screening by mammography frequency, age and comorbidity score as determined by the Charlson Comorbidity Index.Results: Mammography biennially vs. annually for women aged 66–89 years does not increase risk of tumors with unfavorable characteristics regardless of ...

  
  

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

Menée sur trois cohortes de 308, 159 et 149 patientes atteintes d'un cancer du sein, cette étude évalue l'intérêt de détecter la présence de mutations du gène BRCA1 chez les patientes atteintes d'un cancer du sein triple négatif avant 50 ans

• BRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 years
  • British Journal of Cancer, sous presse, 2012 (résumé)
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  Menée sur trois cohortes de 308, 159 et 149 patientes atteintes d'un cancer du sein, cette étude évalue l'intérêt de détecter la présence de mutations du gène BRCA1 chez les patientes atteintes d'un cancer du sein triple négatif avant 50 ans

  “BRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 years”

  • Robertson, L.;Hanson, H.;Seal, S.;Warren-Perry, M.;Hughes, D.;Howell, I.;Turnbull, C.;Houlston, R.;Shanley, S.;Butler, S.;Evans, D. G.;Ross, G.;Eccles, D.;Tutt, A.;Rahman, N.

  Background: Triple-negative (TN) tumours are the predominant breast cancer subtype in BRCA1 mutation carriers. Recently, it was proposed that all individuals below 50 years of age with TN breast cancer should be offered BRCA testing. We have evaluated the BRCA1 mutation frequency and the implications for clinical practice of undertaking genetic testing in women with TN breast cancer. Methods: We undertook BRCA1 mutation analysis in 308 individuals with TN breast cancer, 159 individuals from unselected series of breast cancer and 149 individuals from series ascertained on the basis of young age and/or family history. Results: BRCA1 mutations were present in 45 out of 308 individuals. Individuals with TN cancer <50 years had >10% likelihood of carrying a BRCA1 mutation in both the unselected (11 out of 58, 19%) and selected (26 out of 111, 23%) series. However, over a third would not have been offered testing using existing criteria. We estimate that testing all individuals with TN ...

  
  

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