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Presence of allele frequency heterogeneity defined by ctDNA profiling predicts unfavorable overall survival of NSCLC
- Source :
- Ann Transl Med
- Publication Year :
- 2019
- Publisher :
- AME Publishing Company, 2019.
-
Abstract
- Background The generation of subclonal (low-frequency) mutations is driven by tumor mutations and the relationship between the heterogeneity of tumor mutation abundance and non-small cell lung cancer (NSCLC) remains unknown. We investigate the role of allele frequency heterogeneity (AFH) defined by circulating tumor DNA (ctDNA) profiling in predicting prognosis in advanced NSCLC patients. Methods Publicly available data set of POPLAR (N=211) and OAK (N=642) trials were used for analyzing. A low ratio of allele frequency (AF) of a mutation to the maximum-somatic-allele-frequency (MSAF) was used to define the presence of AFH. The prognostic value of AF/MSAF ratio that was below a defined cutoff point in overall survival (OS) was evaluated using Cox-proportional hazards regression; and the structural break point was determined by LOESS regression and Chow test. The derived AFH was also explored in an independent cohort (N=259) of advanced NSCLC receiving first-line EGFR-TKIs from the First Affiliated Hospital of Guangzhou Medical University. Results In the POPLAR and OAK cohort, low AF/MSAF ratio was found to be significantly associated with unfavorable OS in univariate and multivariate analysis. The structural break point analysis demonstrated that AF/MSAF
- Subjects :
- Oncology
Chemotherapy
medicine.medical_specialty
Multivariate analysis
business.industry
medicine.medical_treatment
030232 urology & nephrology
non-small cell lung cancer (NSCLC)
medicine.disease
Editorial Commentary
03 medical and health sciences
0302 clinical medicine
030220 oncology & carcinogenesis
Internal medicine
Cohort
medicine
Overall survival
Cutoff point
business
Lung cancer
Allele frequency
Subjects
Details
- ISSN :
- 22264477 and 22186751
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Translational Lung Cancer Research
- Accession number :
- edsair.doi.dedup.....bf6b541174bd2591f2606c6fe84703b8