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Published on: August 14, 2019
Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in NSCLC
Qian Cui1, Jia-Tao Zhang2, Huan Yin3
1Department of Pathology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.
Introduction:
Circulating tumor DNA (ctDNA)-based assays enable the detection of minimal residual disease (MRD) after surgery and are predictive of recurrence in patients with lung cancer. However, the optimal technical strategy remains a subject of active debate.
Methods:
We conducted a head-to-head comparison of tumor-naive fixed panel, tumor-informed fixed panel, and tumor-informed personalized panel assays to analyze ctDNA-MRD in 417 plasma samples from 84 patients with stages I to III lung cancer.
Results:
At the landmark time point, the personalized assay achieved superior performance compared with the tumor-naive and tumor-informed assays, with a sensitivity of 40.9% (p = 0.003), a specificity of 100.0% (p < 0.001), a negative predictive value of 81.7% (p < 0.001), and a positive predictive value of 100.0% (p < 0.001). MRD positivity by the personalized assay was associated with significantly shorter disease-free survival (p < 0.001; hazard ratio = 13.98; 95% confidence interval: 1.95-100.37). Longitudinal MRD monitoring using the personalized assay improved relapse prediction, providing a median lead time of 7.0 months before radiologic recurrence.
Conclusion:
The personalized assays may optimize MRD detection and inform individualized postoperative surveillance in lung cancer.
