%0 Journal Article %1 Oberthuer:2010:J-Clin-Oncol:20567016 %A Oberthuer, A %A Hero, B %A Berthold, F %A Juraeva, D %A Faldum, A %A Kahlert, Y %A Asgharzadeh, S %A Seeger, R %A Scaruffi, P %A Tonini, G P %A Janoueix-Lerosey, I %A Delattre, O %A Schleiermacher, G %A Vandesompele, J %A Vermeulen, J %A Speleman, F %A Noguera, R %A Piqueras, M %A Bénard, J %A Valent, A %A Avigad, S %A Yaniv, I %A Weber, A %A Christiansen, H %A Grundy, R G %A Schardt, K %A Schwab, M %A Eils, R %A Warnat, P %A Kaderali, L %A Simon, T %A Decarolis, B %A Theissen, J %A Westermann, F %A Brors, B %A Fischer, M %D 2010 %J J Clin Oncol %K myPublications %N 21 %P 3506-3515 %R 10.1200/JCO.2009.27.3367 %T Prognostic impact of gene expression-based classification for neuroblastoma %U http://www.ncbi.nlm.nih.gov/pubmed/20567016 %V 28 %X To evaluate the impact of a predefined gene expression-based classifier for clinical risk estimation and cytotoxic treatment decision making in neuroblastoma patients.Gene expression profiles of 440 internationally collected neuroblastoma specimens were investigated by microarray analysis, 125 of which were examined prospectively. Patients were classified as either favorable or unfavorable by a 144-gene prediction analysis for microarrays (PAM) classifier established previously on a separate set of 77 patients. PAM classification results were compared with those of current prognostic markers and risk estimation strategies.The PAM classifier reliably distinguished patients with contrasting clinical courses (favorable n = 249 and unfavorable n = 191; 5-year event free survival EFS 0.84 +/- 0.03 v 0.38 +/- 0.04; 5-year overall survival OS 0.98 +/- 0.01 v 0.56 +/- 0.05, respectively; both P < .001). Moreover, patients with divergent outcome were robustly discriminated in both German and international cohorts and in prospectively analyzed samples (P <or= .001 for both EFS and OS for each). In subgroups with clinical low-, intermediate-, and high-risk of death from disease, the PAM predictor significantly separated patients with divergent outcome (low-risk 5-year OS: 1.0 v 0.75 +/- 0.10, P < .001; intermediate-risk: 1.0 v 0.82 +/- 0.08, P = .042; and high-risk: 0.81 +/- 0.08 v 0.43 +/- 0.05, P = .001). In multivariate Cox regression models based on both EFS and OS, PAM was a significant independent prognostic marker (EFS: hazard ratio HR, 3.375; 95% CI, 2.075 to 5.492; P < .001; OS: HR, 11.119, 95% CI, 2.487 to 49.701; P < .001). The highest potential clinical impact of the classifier was observed in patients currently considered as non-high-risk (n = 289; 5-year EFS: 0.87 +/- 0.02 v 0.44 +/- 0.07; 5-year OS: 1.0 v 0.80 +/- 0.06; both P < .001).Gene expression-based classification using the 144-gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients.

@article{Oberthuer:2010:J-Clin-Oncol:20567016, abstract = {To evaluate the impact of a predefined gene expression-based classifier for clinical risk estimation and cytotoxic treatment decision making in neuroblastoma patients.Gene expression profiles of 440 internationally collected neuroblastoma specimens were investigated by microarray analysis, 125 of which were examined prospectively. Patients were classified as either favorable or unfavorable by a 144-gene prediction analysis for microarrays (PAM) classifier established previously on a separate set of 77 patients. PAM classification results were compared with those of current prognostic markers and risk estimation strategies.The PAM classifier reliably distinguished patients with contrasting clinical courses (favorable [n = 249] and unfavorable [n = 191]; 5-year event free survival [EFS] 0.84 +/- 0.03 v 0.38 +/- 0.04; 5-year overall survival [OS] 0.98 +/- 0.01 v 0.56 +/- 0.05, respectively; both P < .001). Moreover, patients with divergent outcome were robustly discriminated in both German and international cohorts and in prospectively analyzed samples (P <or= .001 for both EFS and OS for each). In subgroups with clinical low-, intermediate-, and high-risk of death from disease, the PAM predictor significantly separated patients with divergent outcome (low-risk 5-year OS: 1.0 v 0.75 +/- 0.10, P < .001; intermediate-risk: 1.0 v 0.82 +/- 0.08, P = .042; and high-risk: 0.81 +/- 0.08 v 0.43 +/- 0.05, P = .001). In multivariate Cox regression models based on both EFS and OS, PAM was a significant independent prognostic marker (EFS: hazard ratio [HR], 3.375; 95% CI, 2.075 to 5.492; P < .001; OS: HR, 11.119, 95% CI, 2.487 to 49.701; P < .001). The highest potential clinical impact of the classifier was observed in patients currently considered as non-high-risk (n = 289; 5-year EFS: 0.87 +/- 0.02 v 0.44 +/- 0.07; 5-year OS: 1.0 v 0.80 +/- 0.06; both P < .001).Gene expression-based classification using the 144-gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients.}, added-at = {2015-04-09T16:48:25.000+0200}, author = {Oberthuer, A and Hero, B and Berthold, F and Juraeva, D and Faldum, A and Kahlert, Y and Asgharzadeh, S and Seeger, R and Scaruffi, P and Tonini, G P and Janoueix-Lerosey, I and Delattre, O and Schleiermacher, G and Vandesompele, J and Vermeulen, J and Speleman, F and Noguera, R and Piqueras, M and B{\'e}nard, J and Valent, A and Avigad, S and Yaniv, I and Weber, A and Christiansen, H and Grundy, R G and Schardt, K and Schwab, M and Eils, R and Warnat, P and Kaderali, L and Simon, T and Decarolis, B and Theissen, J and Westermann, F and Brors, B and Fischer, M}, biburl = {https://www.bibsonomy.org/bibtex/2d3a62f54637c76528867b177d261d765/juraeva}, description = {Prognostic impact of gene expression-based classification for neuroblastoma. - PubMed - NCBI}, doi = {10.1200/JCO.2009.27.3367}, interhash = {62d5fd3d9fe549539ca68059dd73d901}, intrahash = {d3a62f54637c76528867b177d261d765}, journal = {J Clin Oncol}, keywords = {myPublications}, month = jul, number = 21, pages = {3506-3515}, pmid = {20567016}, timestamp = {2015-04-09T17:02:23.000+0200}, title = {Prognostic impact of gene expression-based classification for neuroblastoma}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20567016}, volume = 28, year = 2010 }