Quantitative analysis of circulating cell-free DNA for correlation with lung cancer survival: a systematic review and meta-analysis.
http://www.jto.org/article/S1556-0864(16)30711-0/pdf
ABSTRACT
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Introduction: Despite the growing interest in circulating cell-free DNA (cfDNA), no conclusive
evidence exists on the value of quantitative analysis of cfDNA for prediction of lung cancer
survival. We herein performed a systematic review and meta-analysis of primary studies to estimate
the impact of higher baseline cfDNA levels on survival outcomes of lung cancer patients.
Methods: A comprehensive search was performed through PubMed, Web of Knowledge and Cochrane databases up to March 2016. The methodological quality of identified studies was assessed by the Newcastle-Ottawa Scale. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, while publication bias was evaluated by funnel plot and Egger’s test.
Results: Among the 17 studies identified, 16 studies (n=1723 patients) and 5 studies (n=640) were included in the meta-analysis of overall survival (OS) and progression-free survival (PFS), respectively. Despite the association with PFS did not reach statistical significance (HR: 1.12%, 95%CI 0.91-1.37), the pooled analysis for OS showed evidence of an increased risk of death in patients with higher baseline cfDNA levels (HR: 1.76, 95%CI: 1.38-2.25, P<0.001). Further subgroup and sensitivity analyses confirmed this relationship, although significant between-study heterogeneity was still detected in most comparisons. The Egger’s test revealed no statistical evidence of publication bias in the results.
Conclusion: Our findings support clinical validity of quantitative analysis of cfDNA for prediction of lung cancer survival. Nevertheless, the establishment of a robust standardized method for determination of optimal cut-off thresholds is required to define the clinical relevance of cfDNA quantification for lung cancer management.
Key Words: Non–small-cell lung cancer, Circulating cell-free DNA, Survival, Meta-analysis.
Methods: A comprehensive search was performed through PubMed, Web of Knowledge and Cochrane databases up to March 2016. The methodological quality of identified studies was assessed by the Newcastle-Ottawa Scale. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, while publication bias was evaluated by funnel plot and Egger’s test.
Results: Among the 17 studies identified, 16 studies (n=1723 patients) and 5 studies (n=640) were included in the meta-analysis of overall survival (OS) and progression-free survival (PFS), respectively. Despite the association with PFS did not reach statistical significance (HR: 1.12%, 95%CI 0.91-1.37), the pooled analysis for OS showed evidence of an increased risk of death in patients with higher baseline cfDNA levels (HR: 1.76, 95%CI: 1.38-2.25, P<0.001). Further subgroup and sensitivity analyses confirmed this relationship, although significant between-study heterogeneity was still detected in most comparisons. The Egger’s test revealed no statistical evidence of publication bias in the results.
Conclusion: Our findings support clinical validity of quantitative analysis of cfDNA for prediction of lung cancer survival. Nevertheless, the establishment of a robust standardized method for determination of optimal cut-off thresholds is required to define the clinical relevance of cfDNA quantification for lung cancer management.
Key Words: Non–small-cell lung cancer, Circulating cell-free DNA, Survival, Meta-analysis.
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