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J. Pers. Med. 2013, 3(3), 251-262; doi:10.3390/jpm3030251
Article

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

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Received: 30 July 2013; in revised form: 27 August 2013 / Accepted: 30 August 2013 / Published: 12 September 2013
(This article belongs to the Special Issue Feature Paper 2013)
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Abstract: 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.
Keywords: biomarkers; cancer; protein expression; methodology; non-small-cell lung cancer; ERCC1 biomarkers; cancer; protein expression; methodology; non-small-cell lung cancer; ERCC1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

Chen W, Bepler G. A Method for Biomarker Directed Survival Prediction in Advanced Non-Small-Cell Lung Cancer Patients Treated with Carboplatin-Based Therapy. Journal of Personalized Medicine. 2013; 3(3):251-262.

Chicago/Turabian Style

Chen, Wei; Bepler, Gerold. 2013. "A Method for Biomarker Directed Survival Prediction in Advanced Non-Small-Cell Lung Cancer Patients Treated with Carboplatin-Based Therapy." J. Pers. Med. 3, no. 3: 251-262.

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