TY - JOUR
T1 - Prognostic impact of gene expression-based classification for neuroblastoma
AU - Oberthuer, André
AU - Hero, Barbara
AU - Berthold, Frank
AU - Juraeva, Dilafruz
AU - Faldum, Andreas
AU - Kahlert, Yvonne
AU - Asgharzadeh, Shahab
AU - Seeger, Robert
AU - Scaruffi, Paola
AU - Tonini, Gian Paolo
AU - Janoueix-Lerosey, Isabelle
AU - Delattre, Olivier
AU - Schleiermacher, Gudrun
AU - Vandesompele, Jo
AU - Vermeulen, Joëlle
AU - Speleman, Frank
AU - Noguera, Rosa
AU - Piqueras, Marta
AU - Bénard, Jean
AU - Valent, Alexander
AU - Avigad, Smadar
AU - Yaniv, Isaac
AU - Weber, Axel
AU - Christiansen, Holger
AU - Grundy, Richard G.
AU - Schardt, Katharina
AU - Schwab, Manfred
AU - Eils, Roland
AU - Warnat, Patrick
AU - Kaderali, Lars
AU - Simon, Thorsten
AU - DeCarolis, Boris
AU - Theissen, Jessica
AU - Westermann, Frank
AU - Brors, Benedikt
AU - Fischer, Matthias
PY - 2010/7/20
Y1 - 2010/7/20
N2 - Purpose: To evaluate the impact of a predefined gene expression-based classifier for clinical risk estimation and cytotoxic treatment decision making in neuroblastoma patients. Patients and Methods: 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. Results: 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 ≤ .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; intermediaterisk: 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). Conclusion: Gene expression-based classification using the 144-gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients.
AB - Purpose: To evaluate the impact of a predefined gene expression-based classifier for clinical risk estimation and cytotoxic treatment decision making in neuroblastoma patients. Patients and Methods: 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. Results: 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 ≤ .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; intermediaterisk: 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). Conclusion: Gene expression-based classification using the 144-gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients.
UR - http://www.scopus.com/inward/record.url?scp=77955287153&partnerID=8YFLogxK
U2 - 10.1200/JCO.2009.27.3367
DO - 10.1200/JCO.2009.27.3367
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:77955287153
SN - 0732-183X
VL - 28
SP - 3506
EP - 3515
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 21
ER -
