%0 Journal Article %1 Oberthuer:2014rw %A Oberthuer, Andre %A Juraeva, Dilafruz %A Hero, Barbara %A Volland, Ruth %A Carolina, Sterz %A Schmidt, Rene %A Faldum, Andreas %A Kahlert, Yvonne %A Engesser, Anne %A Asgharzadeh, Shahab %A Seeger, Robert C. %A Ohira, Miki %A Nakagawara, Akira %A Scaruffi, Paola %A Tonini, Gian Paolo %A Janoueix-Lerosey, Isabelle %A Delattre, Olivier %A Schleiermacher, Gudrun %A Vandesompele, Jo %A Speleman, Frank %A Noguera, Rosa %A Piqueras, Marta %A Benard, Jean %A Valent, Alexander %A Avigad, Smadar %A Yaniv, Isaac %A Grundy, Richard Guy %A Ortmann, Monika %A Shao, Chunxuan %A Schwab, Manfred %A Eils, Roland %A Simon, Thorsten %A Theissen, Jessica %A Berthold, Frank %A Westermann, Frank %A Brors, Benedikt %A Fischer, Matthias %D 2014 %J Clinical Cancer Research %K myPublications %R 10.1158/1078-0432.CCR-14-0817 %T Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers %U http://clincancerres.aacrjournals.org/content/early/2014/09/16/1078-0432.CCR-14-0817.abstract %X Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression-based classification and established prognostic markers. Material and Methods: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4x44K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n=634) by Kaplan-Meier estimates and Cox regression analyses. Results: The best-performing classifier predicted patient outcome with an accuracy of 0.95 (sensitivity 0.93, specificity 0.97) in the validation cohort. The highest potential clinical value of this predictor was observed for current low-risk patients (LR: 5-year EFS 0.84$\pm$0.02 vs 0.29$\pm$0.10; 5-year OS 0.99$\pm$0.01vs 0.76$\pm$0.11; both p<0.001) and intermediate-risk patients (IR: 5-year EFS 0.88$\pm$0.06 vs 0.41$\pm$0.10; 5-year OS 1.0 vs 0.70$\pm$0.09; both p<0.001). In multivariate Cox regression models for LR/IR patients the classifier outperformed risk assessment of the current German trial NB2004 (EFS: HR 5.07, 95%-CI 3.20-8.02, OS: HR 25.54, 95%-CI 8.40-77.66; both p<0.001). Based on these findings, we propose to integrate the classifier into a revised risk stratification system for LR/IR patients. According to this system, we identified novel subgroups with poor outcome (5-year EFS 0.19$\pm$0.08; 5-year OS 0.59$\pm$0.1), for whom we propose intensified treatment, and with beneficial outcome (5-year EFS 0.87$\pm$0.05; 5-year OS 1.0), who may benefit from treatment de-escalation. Conclusion: Combination of gene expression-based classification and established prognostic markers improves risk estimation of LR/IR neuroblastoma patients. We propose to implement our revised treatment stratification system in a prospective clinical trial.

@article{Oberthuer:2014rw, abstract = {Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression-based classification and established prognostic markers. Material and Methods: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4x44K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n=634) by Kaplan-Meier estimates and Cox regression analyses. Results: The best-performing classifier predicted patient outcome with an accuracy of 0.95 (sensitivity 0.93, specificity 0.97) in the validation cohort. The highest potential clinical value of this predictor was observed for current low-risk patients (LR: 5-year EFS 0.84$\pm$0.02 vs 0.29$\pm$0.10; 5-year OS 0.99$\pm$0.01vs 0.76$\pm$0.11; both p<0.001) and intermediate-risk patients (IR: 5-year EFS 0.88$\pm$0.06 vs 0.41$\pm$0.10; 5-year OS 1.0 vs 0.70$\pm$0.09; both p<0.001). In multivariate Cox regression models for LR/IR patients the classifier outperformed risk assessment of the current German trial NB2004 (EFS: HR 5.07, 95%-CI 3.20-8.02, OS: HR 25.54, 95%-CI 8.40-77.66; both p<0.001). Based on these findings, we propose to integrate the classifier into a revised risk stratification system for LR/IR patients. According to this system, we identified novel subgroups with poor outcome (5-year EFS 0.19$\pm$0.08; 5-year OS 0.59$\pm$0.1), for whom we propose intensified treatment, and with beneficial outcome (5-year EFS 0.87$\pm$0.05; 5-year OS 1.0), who may benefit from treatment de-escalation. Conclusion: Combination of gene expression-based classification and established prognostic markers improves risk estimation of LR/IR neuroblastoma patients. We propose to implement our revised treatment stratification system in a prospective clinical trial.}, added-at = {2015-04-09T16:26:10.000+0200}, author = {Oberthuer, Andre and Juraeva, Dilafruz and Hero, Barbara and Volland, Ruth and Carolina, Sterz and Schmidt, Rene and Faldum, Andreas and Kahlert, Yvonne and Engesser, Anne and Asgharzadeh, Shahab and Seeger, Robert C. and Ohira, Miki and Nakagawara, Akira and Scaruffi, Paola and Tonini, Gian Paolo and Janoueix-Lerosey, Isabelle and Delattre, Olivier and Schleiermacher, Gudrun and Vandesompele, Jo and Speleman, Frank and Noguera, Rosa and Piqueras, Marta and Benard, Jean and Valent, Alexander and Avigad, Smadar and Yaniv, Isaac and Grundy, Richard Guy and Ortmann, Monika and Shao, Chunxuan and Schwab, Manfred and Eils, Roland and Simon, Thorsten and Theissen, Jessica and Berthold, Frank and Westermann, Frank and Brors, Benedikt and Fischer, Matthias}, bdsk-url-1 = {http://clincancerres.aacrjournals.org/content/early/2014/09/16/1078-0432.CCR-14-0817.abstract}, bdsk-url-2 = {http://dx.doi.org/10.1158/1078-0432.CCR-14-0817}, biburl = {https://www.bibsonomy.org/bibtex/200e2d6482a1137fa2b5bc947f44411fa/juraeva}, date-added = {2015-01-20 18:47:14 +0100}, date-modified = {2015-01-20 18:48:07 +0100}, doi = {10.1158/1078-0432.CCR-14-0817}, eprint = {http://clincancerres.aacrjournals.org/content/early/2014/09/16/1078-0432.CCR-14-0817.full.pdf+html}, interhash = {3efc433d30430896e0ffeee8caef4915}, intrahash = {00e2d6482a1137fa2b5bc947f44411fa}, journal = {Clinical Cancer Research}, keywords = {myPublications}, month = {September}, timestamp = {2015-04-09T17:02:23.000+0200}, title = {Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers}, url = {http://clincancerres.aacrjournals.org/content/early/2014/09/16/1078-0432.CCR-14-0817.abstract}, year = 2014 }