Accueil Nota Bene Cancer V2 Numéro 134 du 03 Mai 2012 Dépistage, diagnostic et pronostic

Nota Bene Cancer Numéro 134 du 03 Mai 2012

Dépistage, diagnostic et pronostic

Découverte de technologies et de biomarqueurs

Menée sur des échantillons sanguins prélevés sur 45 patientes atteintes d'un cancer métastatique du sein, cette étude évalue l'intérêt d'une méthode appelée CTCscope pour détecter et caractériser des cellules tumorales circulantes

Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients
• British Journal of Cancer, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur des échantillons sanguins prélevés sur 45 patientes atteintes d'un cancer métastatique du sein, cette étude évalue l'intérêt d'une méthode appelée CTCscope pour détecter et caractériser des cellules tumorales circulantes

“Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients”

• Payne, R. E.;Wang, F.;Su, N.;Krell, J.;Zebrowski, A.;Yague, E.;Ma, X. J.;Luo, Y.;Coombes, R. C.

Background: Current approaches for detecting circulating tumour cells (CTCs) in blood are dependent on CTC enrichment and are based either on surface epithelial markers on CTCs or on cell size differences. The objectives of this study were to develop and characterise an ultrasensitive multiplex fluorescent RNA in situ hybridisation (ISH)-based CTC detection system called CTCscope. This method detects a multitude of tumour-specific markers at single-cell level in blood. Methods: Healthy blood samples spiked with tumour cell lines were used as a model system for the development and initial characterisation of CTCscope. To demonstrate the feasibility of CTC detection in patient blood, duplicate blood samples were drawn from 45 metastatic breast cancer patients for analysis by CTCscope and the CellSearch system. The association of CTCs with the tumour marker CA15-3 and progression-free survival (PFS) were assessed. Results: CTCscope detected CTC transcripts of eight epithelial markers and ...

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

Menée initialement sur 41 échantillons tumoraux prélevés sur des patients atteints d'un adénocarcinome pulmonaire, puis sur 128 échantillons complémentaires, cette étude identifie la présence du phénotype méthylateur des îlots Cpg en association avec un pronostic défavorable

Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma
• Carcinogenesis, sous presse, 2012 (résumé)

Détails

Fermer
Menée initialement sur 41 échantillons tumoraux prélevés sur des patients atteints d'un adénocarcinome pulmonaire, puis sur 128 échantillons complémentaires, cette étude identifie la présence du phénotype méthylateur des îlots Cpg en association avec un pronostic défavorable

“Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma”

• Shinjo, Keiko;Okamoto, Yasuyuki;An, Byonggu;Yokoyama, Toshihiko;Takeuchi, Ichiro;Fujii, Makiko;Osada, Hirotaka;Usami, Noriyasu;Hasegawa, Yoshinori;Ito, Hidemi;Hida, Toyoaki;Fujimoto, Nobukazu;Kishimoto, Takumi;Sekido, Yoshitaka;Kondo, Yutaka

DNA methylation affects the aggressiveness of human malignancies. Cancers with CpG island methylator phenotype (CIMP), a distinct group with extensive DNA methylation, show characteristic features in several types of tumors. In this study, we initially defined the existence of CIMP in 41 lung adenocarcinomas (AdCas) through genome-wide DNA methylation microarray analysis. DNA methylation status of six CIMP markers newly identified by microarray analysis was further estimated in a total of 128 AdCas by bisulfite pyrosequencing analysis, which revealed that 10 (7.8%), 40 (31.3%), and 78 (60.9%) cases were classified as CIMP-high (CIMP-H), CIMP-low, and CIMP-negative, respectively. Notably, CIMP-H AdCas were strongly associated with wild type epidermal growth factor receptor (EGFR), males, and heavy smokers (P=0.0089, 0.0047, 0.0036, respectively). In addition, CIMP-H was significantly associated with worse prognosis; especially among male smokers, CIMP-H was an independent prognostic ...

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

Evaluation des technologies et des biomarqueurs

Ces deux études évaluent, d'une part, les facteurs de risque du cancer du sein pour les femmes entre 40 et 49 ans et, d'autre part, l'intérêt de commencer un dépistage par mammographie à 40 ans pour les femmes à risque

Tipping the Balance of Benefits and Harms to Favor Screening Mammography Starting at Age 40 Years
• Annals of Internal Medicine, Vol. 156 (9), pp. 609-617, 2012 (résumé)

Détails

Fermer
Ces deux études évaluent, d'une part, les facteurs de risque du cancer du sein pour les femmes entre 40 et 49 ans et, d'autre part, l'intérêt de commencer un dépistage par mammographie à 40 ans pour les femmes à risque

“Tipping the Balance of Benefits and Harms to Favor Screening Mammography Starting at Age 40 Years”

• van Ravesteyn, Nicolien T.;Miglioretti, Diana L.;Stout, Natasha K.;Lee, Sandra J.;Schechter, Clyde B.;Buist, Diana S.M.;Huang, Hui;Heijnsdijk, Eveline A.M.;Trentham-Dietz, Amy;Alagoz, Oguzhan;Near, Aimee M.;Kerlikowske, Karla;Nelson, Heidi D.;Mandelblatt, Jeanne S.;de Koning, Harry J.

Background: Timing of initiation of screening for breast cancer is controversial in the United States.Objective: To determine the threshold relative risk (RR) at which the harm–benefit ratio of screening women aged 40 to 49 years equals that of biennial screening for women aged 50 to 74 years.Design: Comparative modeling study.Data Sources: Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and medical literature.Target Population: A contemporary cohort of women eligible for routine screening.Time Horizon: Lifetime.Perspective: Societal.Intervention: Mammography screening starting at age 40 versus 50 years with different screening methods (film, digital) and screening intervals (annual, biennial).Outcome Measures: Benefits: life-years gained, breast cancer deaths averted; harms: false-positive mammography findings; harm–benefit ratios: false-positive findings/life-years gained, false-positive findings/deaths averted.Results of Base-Case ...
Risk Factors for Breast Cancer for Women Aged 40 to 49 Years
• Annals of Internal Medicine, Vol. 156 (9), pp. 635-648, 2012 (résumé)

Détails

Fermer
Ces deux études évaluent, d'une part, les facteurs de risque du cancer du sein pour les femmes entre 40 et 49 ans et, d'autre part, l'intérêt de commencer un dépistage par mammographie à 40 ans pour les femmes à risque

“Risk Factors for Breast Cancer for Women Aged 40 to 49 Years”

• Nelson, Heidi D. ; Zakher, Bernadette ; Cantor, Amy ; Fu, Rongwei ; Griffin, Jessica ; O'Meara, Ellen S. ; Buist, Diana S.M. ; Kerlikowske, Karla ; van Ravesteyn, Nicolien T. ; Trentham-Dietz, Amy ; Mandelblatt, Jeanne S. ; Miglioretti, Diana L.

Background: Identifying risk factors for breast cancer specific to women in their 40s could inform screening decisions.Purpose: To determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor.Data Sources: MEDLINE (January 1996 to the second week of November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter of 2011), Scopus, reference lists of published studies, and the Breast Cancer Surveillance Consortium.Study Selection: English-language studies and systematic reviews of risk factors for breast cancer in women aged 40 to 49 years. Additional inclusion criteria were applied for each risk factor.Data Extraction: Data on participants, study design, analysis, follow-up, and outcomes were abstracted. Study quality was rated by using established criteria, and only studies rated as good or fair were included. Results were summarized by using meta-analysis when ...
Risk-Based Mammography Screening: An Effort to Maximize the Benefits and Minimize the Harms
• Annals of Internal Medicine, Vol. 156 (9), pp. 662-663, 2012 (éditorial)

Détails

Fermer
Ces deux études évaluent, d'une part, les facteurs de risque du cancer du sein pour les femmes entre 40 et 49 ans et, d'autre part, l'intérêt de commencer un dépistage par mammographie à 40 ans pour les femmes à risque

“Risk-Based Mammography Screening: An Effort to Maximize the Benefits and Minimize the Harms”

• Brawley, Otis W.

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

A partir de données portant sur 594 patientes atteintes d'un cancer du sein ER+, cette étude évalue la capacité de six signatures basées sur l'expression de plusieurs gènes pour prédire une récidive chez les patientes recevant seulement un traitement adjuvant au tamoxifène

Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen
• Annals of Oncology, sous presse, 2012 (article en libre accès)

Détails

Fermer
A partir de données portant sur 594 patientes atteintes d'un cancer du sein ER+, cette étude évalue la capacité de six signatures basées sur l'expression de plusieurs gènes pour prédire une récidive chez les patientes recevant seulement un traitement adjuvant au tamoxifène

“Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen”

• Prat, A.;Parker, J. S.;Fan, C.;Cheang, M. C. U.;Miller, L. D.;Bergh, J.;Chia, S. K. L.;Bernard, P. S.;Nielsen, T. O.;Ellis, M. J.;Carey, L. A.;Perou, C. M.

Background: ER-positive (ER+) breast cancer includes all of the intrinsic molecular subtypes, although the luminal A and B subtypes predominate. In this study, we evaluated the ability of six clinically relevant genomic signatures to predict relapse in patients with ER+ tumors treated with adjuvant tamoxifen only.Methods: Four microarray datasets were combined and research-based versions of PAM50 intrinsic subtyping and risk of relapse (PAM50-ROR) score, 21-gene recurrence score (OncotypeDX), Mammaprint, Rotterdam 76 gene, index of sensitivity to endocrine therapy (SET) and an estrogen-induced gene set were evaluated. Distant relapse-free survival (DRFS) was estimated by Kaplan–Meier and log-rank tests, and multivariable analyses were done using Cox regression analysis. Harrell's C-index was also used to estimate performance.Results: All signatures were prognostic in patients with ER+ node-negative tumors, whereas most were prognostic in ER+ node-positive disease. Among the ...

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

Menée sur 84 patients atteints d'un mélanome avec métastases à distance, 18 patients ayant survécu plus de 24 mois après l'observation de métastases et 14 témoins sains, cette étude évalue l'association entre la présence de lymphocytes T circulant répondant à l'un des trois antigènes NY-ESO-1, Melan-A et MAGE-3 et la survie des patients

Functional T Cells Targeting NY-ESO-1 or Melan-A Are Predictive for Survival of Patients With Distant Melanoma Metastasis
• Journal of Clinical Oncology, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur 84 patients atteints d'un mélanome avec métastases à distance, 18 patients ayant survécu plus de 24 mois après l'observation de métastases et 14 témoins sains, cette étude évalue l'association entre la présence de lymphocytes T circulant répondant à l'un des trois antigènes NY-ESO-1, Melan-A et MAGE-3 et la survie des patients

“Functional T Cells Targeting NY-ESO-1 or Melan-A Are Predictive for Survival of Patients With Distant Melanoma Metastasis”

• Weide, Benjamin;Zelba, Henning;Derhovanessian, Evelyna;Pflugfelder, Annette;Eigentler, Thomas K.;Di Giacomo, Anna Maria;Maio, Michele;Aarntzen, Erik H.J.G.;de Vries, I. Jolanda M.;Sucker, Antje;Schadendorf, Dirk;Büttner, Petra;Garbe, Claus;Pawelec, Graham

Purpose To analyze the prognostic relevance of circulating T cells responding to NY-ESO-1, Melan-A, MAGE-3, and survivin in patients with melanoma with distant metastasis.Patients and Methods We examined 84 patients with follow-up after analysis (cohort A), 18 long-term survivors with an extraordinarily favorable course of disease before analysis (> 24 months survival after first occurrence of distant metastases; cohort B), and 14 healthy controls. Circulating antigen-reactive T cells were characterized by intracellular cytokine staining after in vitro stimulation.Results In cohort A patients, the presence of T cells responding to peptides from NY-ESO-1, Melan-A, or MAGE-3 and the M category according to the American Joint Committee on Cancer classification were significantly associated with survival. T cells responding to NY-ESO-1 and Melan-A (hazard ratios, 0.29 and 0.18, respectively) remained independent prognostic factors in Cox regression analysis and were superior to the M ...

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

Cet article passe en revue les travaux récents sur l'usage de profils d'expression de gènes pour le diagnostic et le pronostic des mélanomes

Melanoma molecular classes and prognosis in the postgenomic era
• The Lancet Oncology, Vol. 13 (5), pp. e205-e211, 2012 (résumé)

Détails

Fermer
Cet article passe en revue les travaux récents sur l'usage de profils d'expression de gènes pour le diagnostic et le pronostic des mélanomes

“Melanoma molecular classes and prognosis in the postgenomic era”

• Tremante, Elisa;Ginebri, Agnese;Lo Monaco, Elisa;Frascione, Pasquale;Di Filippo, Franco;Terrenato, Irene;Benevolo, Maria;Mottolese, Marcella;Pescarmona, Edoardo;Visca, Paolo;Natali, Pier Giorgio;Giacomini, Patrizio

Gene expression profiling is a powerful method to classify human tumours on the basis of biological aggressiveness, response to therapy, and outcome for the patient, but its application in melanoma lags behind that of other cancers. From more than 100 articles available on the topic, we selected 14 focusing on patients' outcome. We review and briefly discuss salient findings, and list ten reasons why melanoma molecular classes are not yet used in clinical diagnosis and prognosis. The available evidence suggests that we are on the verge of creating a framework for the use of melanoma molecular classes in prognosis, but so far there is little consensus to put together informative diagnostic and prognostic gene sets.

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

Menée sur 308 patients australiens atteints d'un mélanome métastatique, cette étude prospective évalue, en fonction de l'âge des patients, la présence de diverses mutations du gène BRAF (V600E, V600K, ...) lors du diagnostic et leur association avec l'évolution de la maladie

Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-mutant Metastatic Melanoma
• Clinical Cancer Research, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur 308 patients australiens atteints d'un mélanome métastatique, cette étude prospective évalue, en fonction de l'âge des patients, la présence de diverses mutations du gène BRAF (V600E, V600K, ...) lors du diagnostic et leur association avec l'évolution de la maladie

“Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-mutant Metastatic Melanoma”

• Menzies, Alexander M.;Haydu, Lauren E;Visintin, Lydia;Carlino, Matteo S;Howle, Julie R;Thompson, John F.;Kefford, Richard F.;Scolyer, Richard A;Long, Georgina V.

Purpose: Certain clinicopathologic features correlate with BRAF mutation status in melanoma including younger age and primary subtype. This study sought to determine the BRAF mutation status by age-decade, and whether BRAF-mutant genotypes correlated with clinicopathologic features and outcome in patients with metastatic melanoma. Experimental Design: A prospectively assembled cohort of Australian patients were followed from diagnosis of metastatic melanoma (n=308). Clinicopathologic variables were correlated with BRAF mutational status, genotype, and survival. Results: Forty-six percent of patients had a BRAF mutation; 73% V600E, 19% V600K, and 8% other genotypes. An inverse relationship existed between BRAF mutation prevalence and age-decade (P less than 0.001). All patients less than 30 years and only 25% (greater than or equal to)70 years had BRAF-mutant melanoma. Amongst BRAF-mutant melanoma, the frequency of non-V600E genotypes (including V600K) increased with increasing age. ...

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

Menée sur 133 échantillons de tissus prélevés lors d'une coloscopie, cette étude identifie une signature, basée sur 3 micro-ARNs, susceptible de distinguer un carcinome d'une néoplasie intraépithéliale de haut grade

A microRNA panel to discriminate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissue
• Gut, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur 133 échantillons de tissus prélevés lors d'une coloscopie, cette étude identifie une signature, basée sur 3 micro-ARNs, susceptible de distinguer un carcinome d'une néoplasie intraépithéliale de haut grade

“A microRNA panel to discriminate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissue”

• Wang, Shuyang;Wang, Lei;Bayaxi, Nayima;Li, Jian;Verhaegh, Wim;Janevski, Angel;Varadan, Vinay;Ren, Yiping;Merkle, Dennis;Meng, Xianxin;Gao, Xue;Wang, Huijun;Ren, Jiaqiang;Kuo, Winston Patrick;Dimitrova, Nevenka;Wu, Ying;Zhu, Hongguang

Objective It is a challenge to differentiate invasive carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissues. In this study, microRNA profiles were evaluated in the transformation of colorectal carcinogenesis to discover new molecular markers for identifying a carcinoma in colonoscopy biopsy tissues where the presence of stromal invasion cells is not detectable by microscopic analysis.Methods The expression of 723 human microRNAs was measured in laser capture microdissected epithelial tumours from 133 snap-frozen surgical colorectal specimens. Three well-known classification algorithms were used to derive candidate biomarkers for discriminating carcinomas from adenomas. Quantitative reverse-transcriptase PCR was then used to validate the candidates in an independent cohort of macrodissected formalin-fixed paraffin-embedded colorectal tissue samples from 91 surgical resections. The biomarkers were applied to differentiate carcinomas from high-grade ...

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

Essais de technologies et de biomarqueurs dans un contexte clinique

Menée sur 69 patientes et 1 patient atteints d'un cancer primitif du sein de stade précoce (âge moyen : 61.9 ± 8.1 ans ; durée moyenne de suivi : 22.7 ± 12.6 mois), cette étude évalue l'intérêt d'une tomographie numérique par émission de positrons à base de fluorodésoxyglucose (18F) pour la stadification de la maladie

Defining the Role of PET–CT in Staging Early Breast Cancer
• The Oncologist, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur 69 patientes et 1 patient atteints d'un cancer primitif du sein de stade précoce (âge moyen : 61.9 ± 8.1 ans ; durée moyenne de suivi : 22.7 ± 12.6 mois), cette étude évalue l'intérêt d'une tomographie numérique par émission de positrons à base de fluorodésoxyglucose (18F) pour la stadification de la maladie

“Defining the Role of PET–CT in Staging Early Breast Cancer”

• Groves, Ashley M.;Shastry, Manu;Ben-Haim, Simona;Kayani, Irfan;Malhotra, Anmol;Davidson, Timothy;Kelleher, Tina;Whittaker, Diane;Meagher, Marie;Holloway, Brian;Warren, Ruth M.;Ell, Peter J.;Keshtgar, Mohammed R.

Abstract Introduction. Currently, there is a lack of data on the role of combined positron emission tomography–computed tomography (PET–CT) in the staging of early invasive primary breast cancer. We therefore evaluated the role of 18F-fluorodeoxyglucose (18F-FDG)-PET–CT in this patient population.Methods. We prospectively recruited 70 consecutive patients (69 women, one man; mean age, 61.9 ± 8.1 years) with early primary breast cancer for staging with 18F-FDG-PET–CT. All PET–CT images were interpreted by two readers (independently of each other). A third reader adjudicated any discrepancies. All readers had ≥5 years of specific experience. Ethics board approval and informed consent were obtained.Results. The mean clinical follow-up was 22.7 ± 12.6 months. The primary tumor was identified with PET–CT in 64 of 70 patients. Of the unidentified lesions, surgical pathology revealed two intraductal carcinomas, one invasive tubular carcinoma, and three invasive lobular ...

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

Cette étude évalue la sensibilité, la spécificité et la valeur prédictive positive d'un algorithme, développé à partir de données médicales de 3 152 patientes atteintes d'un cancer du sein de stade I ou II diagnostiqué entre 1993 et 2006, pour estimer le risque de récidive et de tumeur primitive au niveau de l'autre sein

Administrative Data Algorithms to Identify Second Breast Cancer Events Following Early-Stage Invasive Breast Cancer
• Journal of the National Cancer Institute, sous presse, 2012 (résumé)

Détails

Fermer
Cette étude évalue la sensibilité, la spécificité et la valeur prédictive positive d'un algorithme, développé à partir de données médicales de 3 152 patientes atteintes d'un cancer du sein de stade I ou II diagnostiqué entre 1993 et 2006, pour estimer le risque de récidive et de tumeur primitive au niveau de l'autre sein

“Administrative Data Algorithms to Identify Second Breast Cancer Events Following Early-Stage Invasive Breast Cancer”

• Chubak, Jessica;Yu, Onchee;Pocobelli, Gaia;Lamerato, Lois;Webster, Joe;Prout, Marianne N.;Ulcickas Yood, Marianne;Barlow, William E.;Buist, Diana S. M.

Background Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard.Methods We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993–2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second ...

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

A partir de données médicales portant sur 650 patientes atteintes d'un cancer du sein et ayant subi, entre 1997 et 2001, une mastectomie et un curage axillaire non combinés à une radiothérapie (durée médiane de suivi : 10 ans), cette étude identifie les facteurs pronostiques associés au risque de récidive

Mastectomy without radiotherapy: outcome analysis after 10 years of follow-up in a single institution
• Breast Cancer Research and Treatment, sous presse, 2012 (résumé)

Détails

Fermer
A partir de données médicales portant sur 650 patientes atteintes d'un cancer du sein et ayant subi, entre 1997 et 2001, une mastectomie et un curage axillaire non combinés à une radiothérapie (durée médiane de suivi : 10 ans), cette étude identifie les facteurs pronostiques associés au risque de récidive

“Mastectomy without radiotherapy: outcome analysis after 10 years of follow-up in a single institution”

• Botteri, E.;Gentilini, O.;Rotmensz, N.;Veronesi, P.;Ratini, S.;Fraga-Guedes, C.;Toesca, A.;Sangalli, C.;Del Castillo, A.;Rietjens, M.;Viale, G.;Orecchia, R.;Goldhirsch, A.;Veronesi, U.

The aim of this study was to identify the prognostic factors associated with the risk of loco-regional recurrence (LRR) of women undergoing mastectomy and complete axillary dissection without radiotherapy. We analyzed data from 650 women operated between 1997 and 2001 in a single institution. Median follow-up was 10 years. Overall survival was 89.8 % at 5 years and 76.6 % at 10 years. The 10-year cumulative incidence of LRRs was 10.0 % (5.0, 10.5, 15.8, and 18.5 % in patients with 0, 1–3, 4–9, and ≥10 positive lymph nodes (LNs), respectively). Sixty-two (9.5 %) LRRs were observed, 5 (0.8 %) of which occurred in the axillary LNs. Supraclavicular LNs recurrences ( n = 16, 2.5 %) occurred more frequently in patients with four or more positive LNs, Ki-67 ≥ 20 % or extensive peritumoral vascular invasion (PVI). At multivariable analysis, nodal status was the only prognostic factor for local events, while nodal status, Ki-67 and PVI were significant prognostic factors for ...

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

A partir de l'analyse d'échantillons tumoraux prélevés sur 3 093 patientes atteintes d'un cancer du sein ER+, cette étude montre que la valeur pronostique de l'expression de la protéine kinase Aurora A dans les cellules cancéreuses exprimant le récepteur des estrogènes est plus significative que celle de la protéine Ki67

Aurora kinase A outperforms Ki67 as a prognostic marker in ER-positive breast cancer
• British Journal of Cancer, sous presse, 2012 (résumé)

Détails

Fermer
A partir de l'analyse d'échantillons tumoraux prélevés sur 3 093 patientes atteintes d'un cancer du sein ER+, cette étude montre que la valeur pronostique de l'expression de la protéine kinase Aurora A dans les cellules cancéreuses exprimant le récepteur des estrogènes est plus significative que celle de la protéine Ki67

“Aurora kinase A outperforms Ki67 as a prognostic marker in ER-positive breast cancer”

• Ali, H. R.;Dawson, S. J.;Blows, F. M.;Provenzano, E.;Pharoah, P. D.;Caldas, C.

Background : Proliferation has emerged as a major prognostic factor in luminal breast cancer. The immunohistochemical (IHC) proliferation marker Ki67 has been most extensively investigated but has not gained widespread clinical acceptance. Methods : We have conducted a head-to-head comparison of a panel of proliferation markers, including Ki67. Our aim was to establish the marker of the greatest prognostic utility. Tumour samples from 3093 women with breast cancer were constructed as tissue microarrays. We used IHC to detect expression of mini-chromosome maintenance protein 2, Ki67, aurora kinase A (AURKA), polo-like kinase 1, geminin and phospho-histone H3. We used a Cox proportional-hazards model to investigate the association with 10-year breast cancer-specific survival (BCSS). Missing values were resolved using multiple imputation. Results : The prognostic significance of proliferation was limited to oestrogen receptor (ER)-positive breast cancer. Aurora kinase A emerged as the ...

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

Mené sur 210 patients atteints d'un cancer de la prostate présentant un risque intermédiaire ou élevé de récidive, cette étude prospective évalue la sensibilité et la spécificité d'une tomographie numérique par émission de positrons à base de fluorométhylcholine-(18F) dans la stadification ganglionnaire

[18F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node staging of prostate cancer: a prospective study of 210 patients
• BJU International, sous presse, 2012 (résumé)

Détails

Fermer
Mené sur 210 patients atteints d'un cancer de la prostate présentant un risque intermédiaire ou élevé de récidive, cette étude prospective évalue la sensibilité et la spécificité d'une tomographie numérique par émission de positrons à base de fluorométhylcholine-(18F) dans la stadification ganglionnaire

“[18F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node staging of prostate cancer: a prospective study of 210 patients”

• Poulsen, Mads H.;Bouchelouche, Kirsten;Høilund-Carlsen, Poul F.;Petersen, Henrik;Gerke, Oke;Steffansen, Signe Inglev;Marcussen, Niels;Svolgaard, Niels;Vach, Werner;Geertsen, Ulla;Walter, Steen

Study Type – Diagnostic (exploratory cohort)Level of Evidence 2aWhat's known on the subject? and What does the study add?Staging of patients with prostate cancer is the cornerstone of treatment. However, after curative intended therapy a high portion of patients relapse with local and/or distant recurrence. Therefore, one may question whether surgical lymph node dissection (LND) is sufficiently reliable for staging of these patients.Several imaging methods for primary LN staging of patients with prostate cancer have been tested. Acceptable detection rates have not been achieved by CT or MRI or for that matter with PET/CT using the most common tracer fluoromethylcholine (FCH). Other more recent metabolic tracers like acetate and choline seem to be more sensitive for assessment of LNs in both primary staging and re-staging. However, previous studies were small. Therefore, we assessed the value of [18F]FCH PET/CT for primary LN staging in a prospective study of a larger sample and ...

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

A partir d'une revue systématique de la littérature (22 études, 1 663 patients), cette étude australienne évalue, par rapport aux méthodes conventionnelles, la sensibilité, la spécificité et le coût de stratégies de stadification d'un cancer du poumon à petites cellules au moyen de la tomographie par émission de positrons

The Efficacy of PET Staging for Small-Cell Lung Cancer: A Systematic Review and Cost Analysis in the Australian Setting
• Journal of Thoracic Oncology, sous presse, 2012 (résumé)

Détails

Fermer
A partir d'une revue systématique de la littérature (22 études, 1 663 patients), cette étude australienne évalue, par rapport aux méthodes conventionnelles, la sensibilité, la spécificité et le coût de stratégies de stadification d'un cancer du poumon à petites cellules au moyen de la tomographie par émission de positrons

“The Efficacy of PET Staging for Small-Cell Lung Cancer: A Systematic Review and Cost Analysis in the Australian Setting”

• Ruben, Jeremy D.;Ball, David L.

Introduction: This study aimed to establish from the published literature the efficacy of a positron emission tomography (PET)-based strategy for the staging of small-cell lung cancer compared to conventional methods, the potential impact on patient management and outcomes, and cost implications for the Australian health system. Methods: EMBASE, Current Contents, PubMed, and OVID, databases were searched using relevant search terms. Reference lists of identified studies were examined for additional pertinent papers. Literature review identified 22 relevant studies containing data for 1663 patients. Studies were evaluated regarding the adequacy of pathological or clinical correlation of imaging findings. Efficacy of PET-staging was analyzed. The Medicare benefits schedule was used to compare costs of the two strategies. Results: Published data confirm that PET staging has a sensitivity approaching 100% and specificity exceeding 90%. Data suggest that compared to conventional staging, ...

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

Menée sur une cohorte de 1 072 patients présentant une tumeur neuroendocrine du pancréas et ayant reçu un traitement chirurgical (durée de suivi supérieure à 2 ans), cette étude compare la précision et la spécificité de deux systèmes de stadification TNM

TNM Staging of Neoplasms of the Endocrine Pancreas: Results From a Large International Cohort Study
• Journal of the National Cancer Institute, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur une cohorte de 1 072 patients présentant une tumeur neuroendocrine du pancréas et ayant reçu un traitement chirurgical (durée de suivi supérieure à 2 ans), cette étude compare la précision et la spécificité de deux systèmes de stadification TNM

“TNM Staging of Neoplasms of the Endocrine Pancreas: Results From a Large International Cohort Study”

• Rindi, G.;Falconi, M.;Klersy, C.;Albarello, L.;Boninsegna, L.;Buchler, M. W.;Capella, C.;Caplin, M.;Couvelard, A.;Doglioni, C.;Delle Fave, G.;Fischer, L.;Fusai, G.;de Herder, W. W.;Jann, H.;Komminoth, P.;de Krijger, R. R.;La Rosa, S.;Luong, T. V.;Pape, U.;Perren, A.;Ruszniewski, P.;Scarpa, A.;Schmitt, A.;Solcia, E.;Wiedenmann, B.

Background Both the European Neuroendocrine Tumor Society (ENETS) and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization (UICC/AJCC/WHO) have proposed TNM staging systems for pancreatic neuroendocrine neoplasms. This study aims to identify the most accurate and useful TNM system for pancreatic neuroendocrine neoplasms.Methods The study included 1072 patients who had undergone previous surgery for their cancer and for which at least 2 years of follow-up from 1990 to 2007 was available. Data on 28 variables were collected, and the performance of the two TNM staging systems was compared by Cox regression analysis and multivariable analyses. All statistical tests were two-sided. Results Differences in distribution of sex and age were observed for the ENETS TNM staging system. At Cox regression analysis, only the ENETS TNM staging system perfectly allocated patients into four statistically significantly different and equally populated risk ...

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

Menée sur une cohorte de 2 937 patients européens atteints d'un cancer de la prostate traité par prostatectomie radicale (durée médiane de suivi : 49 mois), cette étude évalue la précision de l'indice CAPRA (Cancer of the Prostate Risk Assessment) pour prédire le risque de récidive métastatique

Risk assessment of metastatic recurrence in patients with prostate cancer by using the Cancer of the Prostate Risk Assessment score: results from 2937 European patients
• BJU International, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur une cohorte de 2 937 patients européens atteints d'un cancer de la prostate traité par prostatectomie radicale (durée médiane de suivi : 49 mois), cette étude évalue la précision de l'indice CAPRA (Cancer of the Prostate Risk Assessment) pour prédire le risque de récidive métastatique

“Risk assessment of metastatic recurrence in patients with prostate cancer by using the Cancer of the Prostate Risk Assessment score: results from 2937 European patients”

• Budäus, Lars;Isbarn, Hendrik;Tennstedt, Pierre;Salomon, Georg;Schlomm, Thorsten;Steuber, Thomas;Haese, Alexander;Chun, Felix;Fisch, Margit;Michl, Uwe;Heinzer, Hans;Huland, Hartwig;Graefen, Markus

Study Type – Prognosis (case series)Level of Evidence 4What's known on the subject? and What does the study add?Different tools allow the individual estimation of the various endpoints in patients with prostate cancer. The Cancer of the Prostate Risk Assessment (CAPRA) score is an easy to calculate prediction tool, based on a large population based database. However, little is known about the performance of this prediction tool in European patients.The data obtained in the present study demonstrate differences in tumour characteristics between European patients and the initial development cohort from the USA. However, the concordance index of the CAPRA scores for predicting biochemical recurrence and metastatic recurrence was 76.2 and 78.5, respectively, in European patients. Therefore, the CAPRA score also allows reliable prediction of the examined endpoints in European patients. OBJECTIVES * •To assess the ability of the Cancer of the Prostate Risk Assessment Score (CAPRA) ...

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

Menée sur 54 patients pédiatriques atteints d'un lymphome T lymphoblastique, cette étude française évalue la fréquence et la valeur pronostique de mutations des gènes NOTCH1 et FBXW7, de délétions du gène FLASH du chromosome 6q et de réarrangements sur les récepteurs des lymphocytes T

Clinical Impact of NOTCH1 and/or FBXW7 Mutations, FLASH Deletion, and TCR Status in Pediatric T-Cell Lymphoblastic Lymphoma
• Journal of Clinical Oncology, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur 54 patients pédiatriques atteints d'un lymphome T lymphoblastique, cette étude française évalue la fréquence et la valeur pronostique de mutations des gènes NOTCH1 et FBXW7, de délétions du gène FLASH du chromosome 6q et de réarrangements sur les récepteurs des lymphocytes T

“Clinical Impact of NOTCH1 and/or FBXW7 Mutations, FLASH Deletion, and TCR Status in Pediatric T-Cell Lymphoblastic Lymphoma”

• Callens, Celine;Baleydier, Frederic;Lengline, Etienne;Ben Abdelali, Raouf;Petit, Arnaud;Villarese, Patrick;Cieslak, Agata;Minard-Colin, Veronique;Rullier, Anne;Moreau, Anne;Baruchel, André;Schmitt, Claudine;Asnafi, Vahid;Bertrand, Yves;Macintyre, Elizabeth

Purpose Pediatric T-cell lymphoblastic lymphomas (T-LBL) are commonly treated on T-cell acute lymphoblastic leukemia (T-ALL) -derived protocols. Therapeutic stratification based on response to the prephase treatment and on minimal residual disease assessment is well established in T-ALL but is not easy to extrapolate to T-LBL. The identification of molecular prognostic markers at diagnosis in T-LBL could provide an alternative for early therapeutic stratification. Our study determines the frequency and prognostic value of NOTCH1/FBXW7 mutations (N/Fmut), FLASH deletion at chromosome 6q, and TCR rearrangements in a prospective cohort of pediatric T-LBL.Patients and Methods Pathologic samples were obtained at diagnosis for 54 patients treated according to the EuroLB02 protocol in France. N/Fmut were identified by direct sequencing and allelic dosage was used to detect FLASH and TCRγ deletions, which were interpreted in conjunction with TCRγ, TCRβ, and TCRδ rearrangements.Results ...

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

Menée sur 57 patients adultes atteints d'une leucémie aiguë, cette étude évalue l'association entre un niveau sérique élevé du récepteur soluble de l'interleukine 2, l'expression du CD4 à la surface des cellules blastiques et un pronostic défavorable

High serum levels of soluble interleukin-2 receptor in acute myeloid leukemia: Correlation with poor prognosis and CD4 expression on blast cells
• Cancer Epidemiology, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur 57 patients adultes atteints d'une leucémie aiguë, cette étude évalue l'association entre un niveau sérique élevé du récepteur soluble de l'interleukine 2, l'expression du CD4 à la surface des cellules blastiques et un pronostic défavorable

“High serum levels of soluble interleukin-2 receptor in acute myeloid leukemia: Correlation with poor prognosis and CD4 expression on blast cells”

• Nakase, Kazunori;Kita, Kenkichi;Kyo, Taiichi;Tsuji, Kota;Katayama, Naoyuki

Backgorund: Although increased serum levels of soluble interleukin-2 receptor (sIL-2R) and their clinical importance are well known in mature type lymphoproliferative disorders (LD), little data is available about such information in acute type hematological malignancies. Methods: We examined the serum levels of sIL-2R in 57 adult patients with acute type leukemias: 32 with acute myeloid leukemia (AML), 14 acute lymphoblastic leukemia (ALL) and 11 chronic myelocytic leukemia in blast crisis (CMLBC), and in 29 adult patients with mature type LD, and assessed their cellular and clinical relevance in acute type leukemias. Results: No significant differences were seen in the sIL-2R levels between acute type leukemias and mature type LD. In AML, serum sIL-2R levels were related to the cell surface CD4 expression on blast cells, and patients with higher levels ≧2000 U/ml had a poorer prognosis (lower response to chemotherapy and shorter overall survival). Conclusions : These results ...

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

Menée sur 1 103 patients atteints d'un cancer colorectal de stade II ou III, cette étude montre une association entre une faible ou forte instabilité chromosomique et la survie globale des patients

Chromosomal Instability (CIN) Phenotype, CIN High or CIN Low, Predicts Survival for Colorectal Cancer
• Journal of Clinical Oncology, sous presse, 2012 (résumé)

Détails

Fermer
Menée sur 1 103 patients atteints d'un cancer colorectal de stade II ou III, cette étude montre une association entre une faible ou forte instabilité chromosomique et la survie globale des patients

“Chromosomal Instability (CIN) Phenotype, CIN High or CIN Low, Predicts Survival for Colorectal Cancer”

• Watanabe, Toshiaki;Kobunai, Takashi;Yamamoto, Yoko;Matsuda, Keiji;Ishihara, Soichiro;Nozawa, Keijiro;Yamada, Hideki;Hayama, Tamuro;Inoue, Eisuke;Tamura, Junko;Iinuma, Hisae;Akiyoshi, Takashi;Muto, Tetsuichiro

Purpose To examine whether chromosomal instability (CIN) phenotype, determined by the severity of CIN, can predict survival for stages II and III colorectal cancer (CRC).Patients and Methods We determined microsatellite instability (MSI) and loss of heterozygosity (LOH) status in 1,103 patients (training [n = 845] and validation [n = 258] sets with stages II and III CRC). The LOH ratio was defined as the frequency of LOH in chromosomes 2p, 5q, 17p, and 18q. According to the LOH ratio, non–MSI high tumors were classified as CIN high (LOH ratio ≥ 33%) or CIN low (LOH ratio < 33%). CIN-high tumors were subclassified as CIN high (mild type; LOH ratio < 75%) or CIN high (severe type; LOH ratio ≥ 75%). We used microarrays to identify a gene signature that could classify the CIN phenotype and evaluated its ability to predict prognosis.Results CIN high showed the worst survival (P < .001), whereas there was no significant difference between CIN low and MSI high. CIN high (severe type) ...

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

Ressources et infrastructures (Dépistage)

Cet article passe en revue les perspectives offertes par la nouvelle génération des techniques de séquençage pour la prise en charge du cancer colorectal

Next generation sequencing and a new era of medicine
• Gut, sous presse, 2012 (résumé)

Détails

Fermer
Cet article passe en revue les perspectives offertes par la nouvelle génération des techniques de séquençage pour la prise en charge du cancer colorectal

“Next generation sequencing and a new era of medicine”

• Casey, Graham;Conti, David;Haile, Robert;Duggan, David

Introduction The 10th anniversary of the publication of the first draft sequence of the human genome was celebrated recently, following the launch of the Human Genome Project in 1990.1 Now, 10 years later, a human genome can be sequenced in less than 10 days and soon will be sequenced routinely within a day. This remarkable progress is due to significant advances in DNA sequencing technologies from Sanger sequencing that has been dominant for nearly 30 years to next generation sequencing (NGS, also termed massively parallel sequencing). The ability to rapidly sequence human genomes and to generate genetic, transcriptomic, epigenetic data and other genome-wide data for a relatively small cost opens up numerous opportunities for translation into the clinic over the next few years. Can the knowledge gained through NGS advances lead to personalized medicine for cancer patients? In this review we provide an overview of NGS technologies and the challenges associated with handling massive ...