In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 21 ( 2010-07-20), p. 3506-3515
Abstract:
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; 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). Conclusion Gene expression–based classification using the 144-gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2009.27.3367
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2010
detail.hit.zdb_id:
2005181-5
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