1. Presence of allele frequency heterogeneity defined by ctDNA profiling predicts unfavorable overall survival of NSCLC
- Author
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Jianfu Li, Xiuyu Cai, Jianxing He, Caichen Li, Zisheng Chen, Jun Liu, Wenhua Liang, Hengrui Liang, Dawei Ye, Bo Cheng, Zhanhong Xie, Shen Zhao, Zhichao Liu, Shan Xiong, and Peng Liang
- 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 - 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
- Published
- 2019