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A Method for Biomarker Directed Survival Prediction in Advanced Non-Small-Cell Lung Cancer Patients Treated with Carboplatin-Based Therapy

Karmanos Cancer Institute, Department of Oncology, Wayne State University, Detroit, MI 48201, USA
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J. Pers. Med. 2013, 3(3), 251-262; https://doi.org/10.3390/jpm3030251
Received: 30 July 2013 / Revised: 27 August 2013 / Accepted: 30 August 2013 / Published: 12 September 2013
(This article belongs to the Special Issue Feature Paper 2013)
Platinum-based chemotherapy is a primary treatment of choice for advanced non-small-cell lung cancer (NSCLC). Analytical methods to specifically evaluate biomarkers predictive of therapeutic efficacy have not been developed. Two randomized phase III trials of carboplatin-based chemotherapy in advanced NSCLC were used for learning and validating the predictive value of ERCC1 in situ protein levels, as measured by accurate quantitative analysis (AQUA). A novel Bayesian method was applied to identify the outcome-based threshold in the learning trial only. Overall survival (OS) was assessed by Kaplan-Meier analysis with log rank testing to determine statistical significance in the validating trial. For patients treated with gemcitabine and carboplatin, the median OS was 9.5 months (95% CI 6.7 to 11.8) for the high ERCC1 group compared to 15.6 months (95% CI 11.6 to 24.8) for the low ERCC1 group in the validation trial (log rank p-value = 0.007). The hazard ratio for low ERCC1 was 0.598 (95% CI, 0.394 to 0.908; p = 0.016) relative to high ERCC1 adjusted for age, sex, and histology. Conclusions: Patients with advanced NSCLC could be stratified into high and low ERCC1 expression groups. Patients with low levels benefited from platinum-based chemotherapy, whereas those with high levels did not. View Full-Text
Keywords: biomarkers; cancer; protein expression; methodology; non-small-cell lung cancer; ERCC1 biomarkers; cancer; protein expression; methodology; non-small-cell lung cancer; ERCC1
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Chen, W.; Bepler, G. A Method for Biomarker Directed Survival Prediction in Advanced Non-Small-Cell Lung Cancer Patients Treated with Carboplatin-Based Therapy. J. Pers. Med. 2013, 3, 251-262.

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