Allele frequency and proportion defined by circulating tumor DNA profiling predict tyrosine kinase inhibitors' therapeutic outcomes for non-small cell lung cancer.

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.

• Authors: Jiajia Song, Ling Bai, Jianzhao Zhai, Zhaodan Xin, Liting You, Yi Zhou, Juan Zhou, Binwu Ying
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 149 Issue 4 Pg. 1531-1540 (Apr 2023) ISSN: 1432-1335 [Electronic] Germany
• PMID: 35578031 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Circulating Tumor DNA
• Tyrosine Protein Kinase Inhibitors
• ErbB Receptors
• Protein Kinase Inhibitors

Topics

• Humans
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Lung Neoplasms (drug therapy, genetics, pathology)
• Circulating Tumor DNA (genetics)
• Tyrosine Protein Kinase Inhibitors
• ErbB Receptors (genetics)
• Retrospective Studies
• Mutation
• Protein Kinase Inhibitors (therapeutic use)
• Progression-Free Survival
• Gene Frequency