Abstract
Purpose
Circulating tumor DNA is more and more accessible for patients who cannot undergo biopsy. No consistent conclusion has been reached on whether frequency and proportion of mutations defined by ctDNA profiling can predict therapeutic outcomes.
Methods
One hundred patients with non-small cell lung cancer harboring activating EGFR mutations (exon 19 deletion, L858R and T790M mutation) were collected in West China hospital from December 18, 2017 to December 31, 2019. We retrospectively analyzed the frequency and proportion distribution of ctDNA mutations and its relationship with tyrosine kinase inhibitors therapeutic outcomes.
Results
Patients with lower frequency of sensitizing EGFR mutations (< 3%) had a longer progression-free survival (PFS) time than those with higher frequency (15 months vs. 10 months, p = 0.028). Moreover, patients with the lower ratio of T790M mutation frequency and the maximum-somatic-allele-frequency (T790M/MSAF < 30%) had a less prolonged PFS than those with higher T790M/MSAF (7 months vs. 15 months, p = 0.013).
Conclusion
The frequency and proportion of ctDNA mutations are worth clinical attention in the prediction of therapeutic outcomes.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ctDNA:
-
Circulating tumor DNA
- NSCLC:
-
Non-small cell lung cancer
- NGS:
-
Next-generation sequencing
- ddPCR:
-
Droplet digital PCR
- PFS:
-
Progression-free survival
- MSAF:
-
Maximum-somatic-allele frequency
- TKIs:
-
Tyrosine kinase inhibitors
- NCCN:
-
The National Comprehensive Cancer Network
- OS:
-
Overall survival
- MiSAF:
-
Minimum-somatic-allele frequency
- SMF:
-
Sensitizing mutation frequency
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Acknowledgements
This work was supported by [National Natural Science Foundation Regional Innovation and Development] (grant number [U20A20394]) and [the Projects in the Sichuan Province Science and Technology Support Program] (grant numbers [2020YFS0214], [2020YJ0106] and [2020YFS0511]).
Funding
This work was supported by [National Natural Science Foundation Regional Innovation and Development] (grant number [U20A20394]) and [the Projects in the Sichuan Province Science and Technology Support Program] (grant numbers [2020YFS0214], [2020YJ0106] and [2020YFS0511]).
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JJS collected data, together with JZZ and LB. ZDX and LTY helped to organize and analyze the data; JJS drafted this manuscript and JZ and LB corrected it; ZJ, YZ and BWY supervised this study and provided funding.
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Song, J., Bai, L., Zhai, J. et al. Allele frequency and proportion defined by circulating tumor DNA profiling predict tyrosine kinase inhibitors’ therapeutic outcomes for non-small cell lung cancer. J Cancer Res Clin Oncol 149, 1531–1540 (2023). https://doi.org/10.1007/s00432-022-03992-5
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DOI: https://doi.org/10.1007/s00432-022-03992-5